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FOURTH EDITION

Chemotherapy
and Biotherapy
Guidelines
AND RECOMMENDATIONS
FOR PRACTICE
Edited by
Martha Polovich, PhD, RN, AOCN
MiKaela Olsen, MS, RN, AOCNS
Kristine B. LeFebvre, MSN, RN, AOCN

FOURTH EDITION

Chemotherapy and
Biotherapy Guidelines
and Recommendations
for Practice
Edited by
Martha Polovich, PhD, RN, AOCN
MiKaela Olsen, MS, RN, AOCNS
Kristine B. LeFebvre, MSN, RN, AOCN

Oncology Nursing Society


Pittsburgh, Pennsylvania

ONS Publications Department


Executive Director, Professional Practice and Programs and Publisher:
Elizabeth Wertz Evans, PhD, RN, MPM, CPHQ, CPHIMS, FHIMSS, FACMPE
Director of Publications: Bill Tony, BA, CQIA
Managing Editor: Lisa M. George, BA
Technical Content Editor: Angela D. Klimaszewski, RN, MSN
Staff Editor II: Amy Nicoletti, BA
Copy Editor: Laura Pinchot, BA
Graphic Designer: Dany Sjoen
Editorial Assistant: Judy Holmes
Copyright 2014 by the Oncology Nursing Society. All rights reserved. No part of the material protected by this copyright may be reproduced or utilized in any form, electronic or mechanical, including photocopying, recording, or by an information storage and retrieval system,
without written permission from the copyright owner. For information, write to the Oncology Nursing Society, 125 Enterprise Drive, Pittsburgh,
PA 15275-1214, or visit www.ons.org/practice-resources/permissions-reprints.
Cover image of cisplatin crystals courtesy of NCI Visuals Online, Larry Ostby, photographer.
Library of Congress Cataloging-in-Publication Data
Chemotherapy and biotherapy guidelines and recommendations for practice. -- Fourth edition / edited by Martha Polovich, MiKaela Olsen, Kristine B. LeFebvre.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-935864-33-2
ISBN 978-1-935864-49-3 (E-Book)
I. Polovich, Martha, editor of compilation. II. Olsen, MiKaela M., editor of compilation. III. LeFebvre, Kristine B., editor of compilation. IV. Oncology Nursing Society, issuing body.
[DNLM: 1. Neoplasms--drug therapy--Outlines. 2. Neoplasms--drug therapy--Practice Guideline. 3. Antineoplastic Agents--administration & dosage--Outlines. 4. Antineoplastic Agents--administration & dosage--Practice Guideline. 5. Biological Agents--therapeutic use--Outlines. 6. Biological
Agents--therapeutic use--Practice Guideline. 7. Neoplasms--nursing--Outlines. 8. Neoplasms--nursing--Practice Guideline. QV 18.2]
RC266
616.9940231--dc23
2013039836

Publishers Note
This book is published by the Oncology Nursing Society (ONS). ONS neither represents nor guarantees that the practices described herein
will, if followed, ensure safe and effective patient care. The recommendations contained in this book reflect ONSs judgment regarding the
state of general knowledge and practice in the field as of the date of publication. The recommendations may not be appropriate for use in all
circumstances. Those who use this book should make their own determinations regarding specific safe and appropriate patient-care practices,
taking into account the personnel, equipment, and practices available at the hospital or other facility at which they are located. The editors
and publisher cannot be held responsible for any liability incurred as a consequence from the use or application of any of the contents of this
book. Figures and tables are used as examples only. They are not meant to be all-inclusive, nor do they represent endorsement of any particular
institution by ONS. Mention of specific products and opinions related to those products do not indicate or imply endorsement by ONS. Websites
mentioned are provided for information only; the hosts are responsible for their own content and availability. Unless otherwise indicated, dollar
amounts reflect U.S. dollars.
ONS publications are originally published in English. Publishers wishing to translate ONS publications must contact ONS about licensing
arrangements. ONS publications cannot be translated without obtaining written permission from ONS. (Individual tables and figures that are
reprinted or adapted require additional permission from the original source.) Because translations from English may not always be accurate or
precise, ONS disclaims any responsibility for inaccuracies in words or meaning that may occur as a result of the translation. Readers relying on
precise information should check the original English version.

Printed in the United States of America

Integrity Innovation Stewardship Advocacy Excellence Inclusiveness

Contributors
Editors
Martha Polovich, PhD, RN, AOCN
Oncology Nurse Consultant
Atlanta, Georgia
Chapter 5. Nursing Considerations in Cancer
Treatment; Chapter 8. Infusion-Related Complications
MiKaela Olsen, MS, RN, AOCNS
Oncology and Hematology Clinical Nurse Specialist
Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins Hospital
Baltimore, Maryland
Chapter 9. Side Effects of Cancer Therapy

Kristine B. LeFebvre, MSN, RN, AOCN


Nurse Planner and Project Manager, Education
Department
Oncology Nursing Society
Pittsburgh, Pennsylvania
Chapter 1. Overview of Cancer and Cancer
Treatment; Chapter 2. Drug Development and
Clinical Trials; Chapter 11. Competence in Chemotherapy Administration

Authors
Carol Stein Blecher, RN, MS, AOCN, APNC,
CBPN-C, CBCN
Advanced Practice Nurse/Clinical Educator
Trinitas Comprehensive Cancer Center
Elizabeth, New Jersey
Chapter 7. Pretreatment Care
Paul F. Davis, MSN, RN
Fourth Floor Manager
Duke Raleigh Hospital
Raleigh, North Carolina
Chapter 9. Side Effects of Cancer Therapy
Tracy T. Douglas, RN, MSN
BMT Nurse Manager
Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins Hospital
Baltimore, Maryland
Chapter 9. Side Effects of Cancer Therapy
Cheryl D. Gilbert, RN, MSN, OCN, CBPN-IC
Nurse Navigator
Mercy Womens Center
Oklahoma City, Oklahoma
Chapter 9. Side Effects of Cancer Therapy

Catherine E. Jansen, PhD, RN, AOCNS


Oncology Clinical Nurse Specialist
Kaiser Permanente Medical Center
San Francisco, California
Chapter 9. Side Effects of Cancer Therapy
Anne Katz, PhD, RN
Clinical Nurse Specialist and Sexuality Counselor
CancerCare Manitoba
Manitoba, Canada
Editor, Oncology Nursing Forum
Oncology Nursing Society
Pittsburgh, Pennsylvania
Chapter 9. Side Effects of Cancer Therapy
Alice S. Kerber, MN, APRN, ACNS-BC,
AOCN, APNG
Oncology Clinical Nurse Specialist
Georgia Center for Oncology Research and
Education
Atlanta, Georgia
Chapter 5. Nursing Considerations in Cancer
Treatment

iii
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

iv

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)
Stephanie Shields, PharmD
Clinical Specialist
McKesson Specialty Health
San Francisco, California
Chapter 3. Principles of Antineoplastic Therapy

Denise Menonna-Quinn, RN-BC, MSN,


AOCNS
Nurse Transplant Insurance Coordinator/
Educator
John Theurer Cancer Center at Hackensack
University Medical Center
Hackensack, New Jersey
Chapter 6. Administration Considerations
Paula M. Muehlbauer, RN, MSN, AOCNS
Clinical Nurse Specialist/Academic Educator
Veterans Affairs San Diego Healthcare System
San Diego, California
Chapter 3. Principles of Antineoplastic Therapy;
Chapter 4. Principles of Biotherapy
Carolene B. Robinson, MA, RN, CNS, CBCN,
AOCN
Oncology Clinical Nurse Specialist
UnityPoint HealthTrinity
Moline, Illinois
Chapter 9. Side Effects of Cancer Therapy
Barbara Barnes Rogers, CRNP, MN, AOCN,
ANP-BC
Adult Hematology-Oncology Nurse Practitioner
Fox Chase Cancer Center
Philadelphia, Pennsylvania
Chapter 9. Side Effects of Cancer Therapy
Lisa Schulmeister, MN, RN, ACNS-BC, OCN,
FAAN
Oncology Nursing Consultant
New Orleans, Louisiana
Chapter 8. Infusion-Related Complications
Nonniekaye Shelburne, CRNP, MS, AOCN
Program Director
National Cancer Institute
Bethesda, Maryland
Chapter 3. Principles of Antineoplastic Therapy;
Chapter 4. Principles of Biotherapy
Brenda K. Shelton, MS, RN, CCRN, AOCN
Clinical Nurse Specialist
Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins Hospital
Baltimore, Maryland
Chapter 9. Side Effects of Cancer Therapy

Janice L. Skinner, RN, MS, MSN, CRNP


Nurse Practitioner
Transplant and Oncology Infectious Diseases
Johns Hopkins School of Medicine
Baltimore, Maryland
Chapter 9. Side Effects of Cancer Therapy
Michael Smart, RN, BSN, OCN
Oncology Nurse Educator, Charge Nurse
Huntsville Hospital
Huntsville, Alabama
Chapter 7. Pretreatment Care
Michael Steinberg, PharmD, BCOP
Associate Professor of Pharmacy Practice
Massachusetts College of Pharmacy and
Health Sciences University
Worcester, Massachusetts
Chapter 4. Principles of Biotherapy
Wendy Stiver, RN, CCM, BSN, MA
Clinical Assessment NurseCase Manager
Alere Health
Atlanta, Georgia
Chapter 1. Overview of Cancer and Cancer
Treatment
Barbara J. Wilson, MS, RN, AOCN, ACNSBC
Director, Oncology Professional Practice
WellStar Kennestone Regional Medical Center
Marietta, Georgia
Chapter 9. Side Effects of Cancer Therapy
Laura J. Zitella, MS, RN, ACNP-BC, AOCN
Lead Advanced Practice Provider, Hematology
and Oncology Nurse Practitioner
Stanford University Medical Center
Stanford, California
Chapter 10. Post-Treatment Care

Field Reviewers
Jill Benedeck, BSN, RN, OCN
Oncology Nurse Educator
Centegra Health System
McHenry, Illinois
James Breedon, RN, BSN, OCN, REMT-P
Nurse Educator
Dendreon Corporation
Albuquerque, New Mexico

Amy S. Coghill, MSN, RN, OCN, CNL


Instructional Designer
Health Care Information Services Division
University of North Carolina Health Care System
Chapel Hill, North Carolina
S. Gayle Marble, BSN, RN, OCN
Director, Oncology Service Line Clinical Education
Banner Health Clinical Education
Phoenix, Arizona

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Contributors

Disclosure
Editors and authors of books and guidelines provided by the Oncology Nursing Society are expected to disclose to the readers any significant financial interest or other relationships with the
manufacturer(s) of any commercial products.
A vested interest may be considered to exist if a contributor is affiliated with or has a financial interest in commercial organizations that may have a direct or indirect interest in the subject matter.
A financial interest may include, but is not limited to, being a shareholder in the organization; being an employee of the commercial organization; serving on an organizations speakers bureau; or
receiving research from the organization. An affiliation may be holding a position on an advisory
board or some other role of benefit to the commercial organization. Vested interest statements appear in the front matter for each publication.
Contributors are expected to disclose any unlabeled or investigational use of products discussed
in their content. This information is acknowledged solely for the information of the readers.
The contributors provided the following disclosure and vested interest information:
Martha Polovich, PhD, RN, AOCN: BD, ICU Medical, honoraria
Kristine B. LeFebvre, MSN, RN, AOCN: American Nurses Credentialing Center, employment or
leadership position
Alice S. Kerber, MN, APRN, ACNS-BC, AOCN, APNG: Pfizer, honoraria
Barbara Barnes Rogers, CRNP, MN, AOCN, ANP-BC: Millennium, Seattle Genetics, Teva, honoraria
Lisa Schulmeister, MN, RN, ACNS-BC, OCN, FAAN: American Society of Clinical Oncology QCP
Program, Intellisphere, consultant
Barbara J. Wilson, MS, RN, AOCN, ACNS-BC: Amgen, honoraria

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table of Contents
Preface........................................................................................................ ix
Abbreviations Used.......................................................................................... xi
Chapter 1. Overview of Cancer and Cancer Treatment..................................................1
A. Definition of cancer...................................................................................................................1
B. Cancer grading and staging......................................................................................................2
C. Cancer treatment modalities ....................................................................................................3
D. Treatment approaches..............................................................................................................5
E. Treatment strategies.................................................................................................................6
F. Goals of cancer therapy: Treatment planning includes discussion with patients about their goals
of therapy and whether those goals are realistic (Skeel, 2011b)...............................................7
G. Measuring response.................................................................................................................7
H. Factors affecting treatment response .....................................................................................10
References.....................................................................................................................................13
Chapter 2. Drug Development and Clinical Trials..................................................... 17
A. Development of new cytotoxic and other therapeutic agents..................................................17
B. Clinical trials involving humans..............................................................................................17
C. Expedited approval..................................................................................................................23
References.....................................................................................................................................23
Chapter 3. Principles of Antineoplastic Therapy....................................................... 25
A. Life cycle of cells....................................................................................................................25
B. Chemotherapeutic agents.......................................................................................................25
References.....................................................................................................................................48
Chapter 4. Principles of Biotherapy...................................................................... 51
A. Immunology...........................................................................................................................51
B. Types of immune response ....................................................................................................51
C. Cells of the immune system....................................................................................................54
D. Tumor escape mechanisms....................................................................................................55
E. Overview of biologic therapies................................................................................................56
F. Categories of biotherapy ........................................................................................................56
G. Radioimmunotherapy.............................................................................................................58
H. Therapeutic uses for biotherapeutic agents............................................................................60
I. Supportive uses for biotherapeutic agents..............................................................................60
J. Biotherapeutic strategies........................................................................................................60
K. Angiogenesis and antiangiogenic agents................................................................................93
References.....................................................................................................................................94
Chapter 5. Nursing Considerations in Cancer Treatment............................................. 97
A. Ethical issues..........................................................................................................................97
B. Legal issues related to cancer therapy....................................................................................99
C. Safety standards for antineoplastic administration...............................................................100
D. Patient safety........................................................................................................................100
E. Safe handling and disposal of hazardous drugs....................................................................102
References...................................................................................................................................115
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

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viii

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)
Chapter 6. Administration Considerations.............................................................121
A. Routes of administration.......................................................................................................121
B. Adherence to therapy............................................................................................................129
C. Pretreatment nursing assessment........................................................................................130
References...................................................................................................................................133
Chapter 7. Pretreatment Care............................................................................137
A. Patient education..................................................................................................................137
B. Verification and maintenance of treatment as planned..........................................................139
References...................................................................................................................................151
Chapter 8. Infusion-Related Complications...........................................................155
A. Types of infusion complications............................................................................................155
B. Extravasation........................................................................................................................155
C. Irritation................................................................................................................................161
D. Flare reaction........................................................................................................................163
E. Acute infusion reactions.......................................................................................................163
F. Patient and caregiver education ...........................................................................................167
References...................................................................................................................................168
Chapter 9. Side Effects of Cancer Therapy.............................................................171
A. Myelosuppression.................................................................................................................171
B. Gastrointestinal and mucosal side effects.............................................................................190
C. Cutaneous toxicity................................................................................................................231
D. Alopecia ...............................................................................................................................250
E. Cardiovascular toxicity..........................................................................................................255
F. Pulmonary toxicity ...............................................................................................................287
G. Hemorrhagic cystitis.............................................................................................................318
H. Hepatotoxicity.......................................................................................................................321
I. Nephrotoxicity.......................................................................................................................329
J. Neurotoxicity.........................................................................................................................337
K. Cognitive impairment............................................................................................................347
L. Ocular toxicity.......................................................................................................................365
M. Pancreatitis...........................................................................................................................375
N. Fatigue..................................................................................................................................377
O. Alterations in sexuality..........................................................................................................383
P. Reproductive alterations.......................................................................................................388
References...................................................................................................................................391
Chapter 10. Post-Treatment Care .......................................................................437
A. Overview...............................................................................................................................437
B. Survivorship care .................................................................................................................437
C. Late effects of cancer treatment............................................................................................438
D. Types of late effects..............................................................................................................440
E. Risk of late effects for patients with select primary cancers.................................................451
F. Collaborative management ...................................................................................................454
G. Nursing assessment ............................................................................................................455
H. Preventive screening recommendations and follow-up care.................................................455
I. Patient and family education ................................................................................................456
J. Professional education..........................................................................................................456
References...................................................................................................................................457
Chapter 11. Competence in Chemotherapy Administration.........................................461
A. Professional education..........................................................................................................461
B. Policies and procedures........................................................................................................463
C. Sample documentation tools................................................................................................463
References...................................................................................................................................464
Appendices.................................................................................................465
Index.........................................................................................................473
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Preface
Welcome to the fourth edition of the Oncology Nursing Societys (ONSs) Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. This book comes
more than 30 years after ONS published its first chemotherapy guidelines. Oncology
nursing practice related to pharmacologic cancer treatment has changed significantly over the years. Not only do more patients undergo drug treatment for cancer today compared to patients diagnosed a generation ago, but patients survival time has
increased, making them more likely to receive treatment over extended periods of
time. The need for evidence-based guidelines for nurses administering chemotherapy and biotherapy is greater than ever.
This new edition incorporates a number of significant changes. The content has
been reorganized and is divided into 11 chapters, with references appearing at the
end of each chapter. We hope that this new way of organizing the material will make
it easier to locate information. The section related to nursing considerations now incorporates the American Society of Clinical Oncology/ONS Chemotherapy Administration Safety Standards (Neuss et al., 2013). All nurses who administer antineoplastic agents must familiarize themselves with and adapt their practices to conform to
these standards. Patient education content has been expanded to emphasize its importance to patient care. The cancer treatment section includes information about
sequencing of chemotherapy agents. The chapter on nursing management of treatment side effects has been updated to reflect existing evidence.
Patients expect nurses to possess the knowledge and skills to provide excellent
care. It is difficult for nurses caring for patients receiving chemotherapy, biotherapy,
and targeted agents to keep up with treatment-related information. These guidelines
are as current as possible with respect to approved drugs, standards of practice, and
available evidence. As always, oncology nurses are encouraged to update their knowledge on an ongoing basis.
The editors want to thank all the contributors to this edition and all the previous
editions of the guidelines. This work builds on the expertise of a whole generation
of chemo nurses. We are proud to be a part of this dedicated group of professionals. We hope these guidelines serve as an essential resource for practicing oncology
nurses today.

Neuss, M.N., Polovich, M., McNiff, K., Esper, P., Gilmore, T., LeFebvre, K.B., Jacobson, J. (2013).
2013 updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards including standards for the safe administration and management of oral chemotherapy. Oncology Nursing Forum, 40, 225233. doi:10.1188/13.ONF.40-03AP2

ix
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Abbreviations Used
ACEangiotensin-converting enzyme
ADHantidiuretic hormone
AHRQAgency for Healthcare Research and
Quality
AJCCAmerican Joint Committee on Cancer
AKIacute kidney injury
AMLacute myeloid leukemia
ANCabsolute neutrophil count
APHONAssociation of Pediatric Hematology/
Oncology Nurses
APLacute promyelocytic leukemia
ARBangiotensin receptor blocker
ASCOAmerican Society of Clinical Oncology
ASHPAmerican Society of Health-System
Pharmacists
ATIacute tubular injury
ATRAall-trans-retinoic acid
AUCarea under the time-versus-concentration curve
BMTbone marrow transplantation
BSAbody surface area
BSCbiologic safety cabinet
BUNblood urea nitrogen
CACIcompounding aseptic containment isolator
CAMcomplementary and alternative medicine
CBCcomplete blood count
CDcluster of differentiation
CDCCenters for Disease Control and Prevention
CDKcyclin-dependent kinase
CHFcongestive heart failure
CIconfidence interval
CINchemotherapy-induced neutropenia
CINVchemotherapy-induced nausea and
vomiting
CKDchronic kidney disease
CMSCenters for Medicare and Medicaid Services
CNcranial nerve
CNScentral nervous system
COGChildrens Oncology Group
CrClcreatinine clearance
CSFcolony-stimulating factor
CSTDclosed-system transfer device
CTcomputed tomography
CTCAECommon Terminology Criteria for Adverse Events
CTEPCancer Therapy Evaluation Program
(NCI)
CTLA-4cytotoxic T-lymphocyte antigen 4
CTZchemoreceptor trigger zone
CVCcentral venous catheter
CVDcardiovascular disease

DHHSU.S. Department of Health and Human


Services
DICdisseminated intravascular coagulation
DLCOdiffusing capacity of the lung for carbon monoxide
DNAdeoxyribonucleic acid
ECGelectrocardiogram
ECMextracellular matrix
ECOGEastern Cooperative Oncology Group
EGFepidermal growth factor
EGFRepidermal growth factor receptor
EGFRIepidermal growth factor receptor inhibitor
18
F-FDGfluorine-18 fluorodeoxyglucose
EORTCEuropean Organization for Research
and Treatment of Cancer
EPOerythropoietin
ERestrogen receptor
ESAerythropoiesis-stimulating agent
estCrClestimated creatinine clearance
FDAU.S. Food and Drug Administration
5-FU5-fluorouracil
5-HT35-hydroxytryptamine-3 (serotonin)
Ggap phase (G0, G1, G2)
G-CSFgranulocytecolony-stimulating factor
GFRglomerular filtration rate
GIgastrointestinal
GM-CSFgranulocyte macrophagecolonystimulating factor
GVHDgraft-versus-host disease
Gygray (radiation unit)
Hhistamine (H1, H2)
HChemorrhagic cystitis
Hcthematocrit
HDhazardous drug
HEPAhigh-efficiency particulate air
HER2human epidermal growth factor receptor 2
Hgbhemoglobin
HIF-1hypoxia-inducible factor-1
HIVhuman immunodeficiency virus
HLHodgkin lymphoma
HPVhuman papillomavirus
HSChematopoietic stem cell
HSCThematopoietic stem cell transplantation
IARCInternational Agency for Research on
Cancer
ICinformed consent
IFNinterferon
IFRTinvolved-field radiation therapy
Igimmunoglobulin (IgA, IgD, IgE)
ILinterleukin
ILDinterstitial lung disease
IMintramuscular

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)
INRinternational normalized ratio
IPintraperitoneal
IRBinstitutional review board
ITintrathecal
IVintravenous
KPSKarnofsky Performance Status
LFTliver function test
LLNlower limit of normal
LVEFleft ventricular ejection fraction
Mmitosis phase
mAbmonoclonal antibody
MASCCMultinational Association of Supportive Care in Cancer
mclmicroliter
MDAUniversity of Texas MD Anderson Cancer Center (classification system)
MDRmultidrug resistance
MDSmyelodysplastic syndrome
MHCmajor histocompatibility complex
MLLmixed lineage leukemia
MMPmatrix metalloproteinase
MOPPmechlorethamine, vincristine, procarbazine, and prednisone
MRImagnetic resonance imaging
mRNAmessenger ribonucleic acid
mTORmammalian target of rapamycin
MUGAmultigated acquisition
NCCNNational Comprehensive Cancer Network
NCINational Cancer Institute
NF-Bnuclear factor-B
NHLnon-Hodgkin lymphoma
NIHNational Institutes of Health
NIOSHNational Institute for Occupational
Safety and Health
NKnatural killer
NK1neurokinin-1
NKTnature killer T
NPnurse practitioner
NRCU.S. Nuclear Regulatory Commission
NSAIDnonsteroidal anti-inflammatory drug
n/vnausea and vomiting
OHRPOffice for Human Research Protections
ONSOncology Nursing Society
OSHAOccupational Safety and Health Administration
PABApara-aminobenzoic acid
PDE5phosphodiesterase-5

PECprimary engineering control


PEGpolyethylene glycol
PEPPutting Evidence Into Practice (ONS)
PERCISTPositron Emission Tomography Response Criteria in Solid Tumors
PETpositron-emission tomography
P-gpP-glycoprotein
PPEpersonal protective equipment
PRprogesterone receptor
PRESposterior reversible encephalopathy
syndrome
PTprothrombin time
PTTpartial thromboplastin time
QOLquality of life
RBCred blood cell
RDIrelative dose intensity
RECISTResponse Evaluation Criteria in Solid Tumors
RITradioimmunotherapy
RRrelative risk
RSOradiation safety officer
Ssynthesis phase
SCsubcutaneous
SCrserum creatinine
SDSsafety data sheet
SIADHsyndrome of inappropriate antidiuretic hormone
SMNsecond malignant neoplasm
TCcytotoxic T cell
TECtoxic erythema of chemotherapy
THhelper T cell (TH1, TH2)
TLStumor lysis syndrome
TMmemory T cell
TNFtumor necrosis factor
TNMtumor, node, metastasis
Tregregulatory T cell
TSsuppressor T cell
USPU.S. Pharmacopeial Convention
UVultraviolet (UVA, UVB)
VADvascular access device
VCvomiting center
VEGFvascular endothelial growth factor
VEGFRvascular endothelial growth factor receptor
VODveno-occlusive disease
VTEvenous thromboembolism
WBCwhite blood cell
WHOWorld Health Organization

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 1

Overview of Cancer and


Cancer Treatment
A. Definition of cancer
1. Clinically, cancer is a large group of malignant diseases with some or all
of the following characteristics (Eggert, 2010; Merkle, 2011).
a) Abnormal cell proliferation caused by a series of cellular and/or genetic alterations or translocations
b) Lack of controlled growth and cell division that leads to the formation of tumors and invasion of tissues in proximity to tumor cells
c) Ability to spread (metastasize) to distant sites and establish secondary tumors
d) Ability to involve any tissue of the body
e) Evasion of natural cell death (apoptosis)
2. On the cellular and molecular levels, however, cancer is believed to be only
a few diseases (Eggert & Kasse, 2010) that result from faulty or abnormal
genetic expression caused by changes in deoxyribonucleic acid (DNA).
a) The transcription of DNA into a single strand of messenger ribonucleic acid (mRNA) may be changed.
b) When abnormal mRNA exists, the sequence of amino acids is changed,
resulting in abnormal protein synthesis.
3. Multiple factors often interact, leading to the development of cancer. Normal
cells may undergo changes outlined by Eggert and Kasse (2010) because of
a) Spontaneous transformation: No causative agent is identified, but cellular characteristics are typical of cancer cells.
b) Exposure to chemical or physical carcinogens: Environmental factors are continuously being studied. Chronic or occupational exposure to substances such as asbestos, benzene, radiation, tobacco, arsenic, nickel, and some chemotherapeutic agents is implicated in cancer development. The National Institute for Occupational Safety and
Health (NIOSH) and other organizations have identified more than
100 substances as carcinogens, with the listings continually evaluated
and revised (International Agency for Research on Cancer [IARC],
2013; National Toxicology Program, 2011; U.S. Department of Health
and Human Services [DHHS], 2012).
c) Genetic alterations: Mutations are permanent changes in the sequencing of DNA base pairs resulting in a cell with malignant properties.
Some mutations are of no concern, whereas others lead to tumor formation (Eggert & Kasse, 2010; Merkle, 2011).
(1) A small percentage of cancers are caused by mutations inherited between generations in germ cells (sperm and ova).
(2) Most cancers are sporadic and caused by a series of acquired
mutations over time.
d) Exposure to viruses: Genetic changes can occur to cells through viral infections. For example, the human papillomavirus (HPV) is the
primary cause of cervical cancer (Fair, 2011).
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

4. Figure 1 provides a summary of genetic changes that may result in tumor formation. The properties of transformed cells are changes in the
cytology, cell membrane, and growth and development.

Figure 1. Clonal Evolution in Cancer


Variant 1

Carcinogen

Normal
clone

First mutation

Variant 3

Variant 2

Selective growth
advantage of clone
with first mutation

Second mutation

Selective growth
advantage of clone
with first and second
mutations

Continuing
evolution of
variant
subpopulations

Third mutation

Specific genetic alterations in evolving tumors may range from gene mutations to major chromosomal aberrations. This figure illustrates
a carcinogen-induced genetic change in a progenitor normal cell (P), which produces a cell with selective growth advantage allowing
clonal expansion to begin. In this case, gene mutations produce variant cells. Because they are at a disadvantage metabolically or immunologically, most variant cells are nonviable. If one variant has a selective advantage, its progeny become the predominant subpopulation until another variant appears. The sequential selection of variant subpopulations in each tumor (T) differs because of genetic instability, which positively or negatively affects cell proliferation.
Note. From Biology of Cancer (p. 7), by C.J. Merkle in C.H. Yarbro, D. Wujcik, and B.H. Gobel (Eds.), Cancer Nursing: Principles and Practice (7th ed.),
2011, Burlington, MA: Jones and Bartlett. Copyright 2011 by Jones and Bartlett. Reprinted with permission.

B. Cancer grading and staging


1. Differentiation and grading: Cellular differentiation is based on how
closely tumor cells resemble normal cells in their structure and maturity. Differentiation is graded using the following scale.
a) GXgrade cannot be assessed
b) G1well differentiated (resembles the parent cell)
c) G2moderately well differentiated
d) G3poorly differentiated (bears little resemblance to the parent cell)
e) G4undifferentiated (impossible to tell which cell is the parent)
f) Cells are obtained by biopsy or surgical removal for microscopic examination by a pathologist. Cancer cells appear different from those
of the surrounding normal tissue. Tumor differentiation can vary over
time, and cells with several grades of differentiation can exist within a single tumor. Tumor grade is a prognostic indicator. The higher
the grade, the more aggressive the tumor (American Joint Committee on Cancer [AJCC], 2010; Vogel, 2011).
2. Staging: The purpose of staging is to verify the extent of the disease by
assessing the location and size of the primary tumor and determining
if it has spread to other tissues or organs. Staging assists in determining
prognosis, treatment planning, identification of suitable clinical trials,
and treatment response. Staging provides a common language with which
the healthcare team can communicate about a patients case. Staging criteria are unique for each type of cancer (AJCC, 2010; National Cancer
Institute [NCI], 2013).
a) AJCC (2010) describes three types of staging: clinical (based on physical examination, imaging, and biopsy), pathologic (based on information obtained during surgery), and restaging (completed upon
disease recurrence).
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Chapter 1. Overview of Cancer and Cancer Treatment

b) The tumor, node, metastasis (TNM) staging system is maintained


jointly by AJCC and the Union for International Cancer Control. It
is used commonly with solid tumors and classifies cancers by the following three criteria. Additional information about cancer staging is
available online at www.cancerstaging.org (AJCC, 2010; Vogel, 2011).
(1) Ttumor (local involvement, invasion): The primary tumor
is measured to document its size and to determine the depth
of invasion.
(2) Nnode (nodal involvement): Lymph nodes in the area of the
primary tumor are examined for evidence of tumor cells. Lymph
node size, number, and location are documented.
(3) Mmetastasis: Studies are done to determine if the primary tumor has metastasized to a distant location.
c) Lymphomas, leukemias, and multiple myeloma are hematologic malignancies that are staged according to other systems. For example, the
Ann Arbor staging classification is used to stage Hodgkin lymphoma
(HL), and the International Staging System is used for multiple myeloma (Gospodarowicz, 2009; Tariman & Faiman, 2011; Vogel, 2011).
d) Childhood cancers may be staged by the TNM system or by criteria
from the Childrens Oncology Group (COG), which conducts clinical trials in pediatric oncology (NCI, 2013).
e) Some gynecologic cancers are staged using the International Federation of Gynecology and Obstetrics, or FIGO, system.
f) Prognostic information is provided by an increasing number of nonanatomic factors that may predict the effectiveness of specific therapies. Gender, overall health status, and specific biologic properties of
tumor cells are characteristics that may affect patient outcomes and
have been incorporated into some staging algorithms (AJCC, 2010).
C. Cancer treatment modalities
1. Table 1 summarizes the history of cancer therapy. A variety of modalities are used to treat cancer. Treatment may include one or more of the
following interventions.

Table 1. History of Cancer Therapy


Period

Events

Pre-20th century

1500s: Heavy metals are used systemically to treat cancers; however, their effectiveness is limited and their
toxicity is great (Burchenal, 1977).
1890s: William Coley, MD, develops and explores the use of Coley toxins, the first nonspecific immunostimulants used to treat cancer.

World War I

Sulfur-mustard gas is used for chemical warfare; servicemen who are exposed to nitrogen mustard experience bone marrow and lymphoid suppression (Gilman, 1963; Gilman & Philips, 1946).

World War II

Congress passes National Cancer Act in 1937, establishing the National Cancer Institute (NCI).
Alkylating agents are recognized for their antineoplastic effect (Gilman & Philips, 1946).
Thioguanine and mercaptopurine are developed (Guy & Ingram, 1996).
1946: NCI-identified cancer research areas include biology, chemotherapy, epidemiology, and pathology.
1948: Divisions within NCI and external institutions are identified to conduct research (Zubrod, 1984).
Folic acid antagonists are found to be effective against childhood acute leukemia (Farber et al., 1948).
Antitumor antibiotics are discovered.

1950s

1955: The National Chemotherapy Program, developed with Congressional funding, is founded to develop
and test new chemotherapy drugs.
1957: Interferon is discovered.
The Childrens Cancer Group, the first cooperative group dedicated to finding effective treatments for pediatric cancer, is formed.
(Continued on next page)

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Table 1. History of Cancer Therapy (Continued)


Period

Events

1960s1970s

Development of platinum compounds begins.


Multidrug therapy improves remission rates without severe toxicity; mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), the first combination chemotherapy, is used and found to be curative against
Hodgkin disease (Noonan, 2007).
Clinical trials of bacillus Calmette-Gurin and Corynebacterium parvum, nonspecific immunostimulants, begin.
Chemotherapy is used with surgery and radiation as cancer treatment.
Development of hybridoma technology begins.
NCI starts its Biological Response Modifiers Program.
Tamoxifen is synthesized in 1962 and first used in 1969.

1970s

The National Cancer Act of 1971 provides funding for cancer research; NCI director is appointed by and reports to the president of the United States.
Doxorubicin phase I trials begin.
Adjuvant chemotherapy begins to be a common cancer treatment (Bonadonna et al., 1985; Fisher et al.,
1986).

1980s

Community Clinical Oncology Programs are developed in 1983 to contribute to NCI chemotherapy clinical trials.
Use of multimodal therapies increases (Eilber et al., 1984; Marcial et al., 1988).
Focus turns to symptom management to alleviate dose-limiting toxicities related to neutropenia, nausea and
vomiting, and cardiotoxicity.
Clinical trials for dexrazoxane (ICRF-187) as a cardioprotectant begin (Speyer et al., 1988).
New chemotherapeutic agents are available.
Scientists begin to investigate recombinant DNA technology.
Trials of monoclonal antibodies and cytokines begin.
Effector cells (lymphokine-activated killer cells and tumor-infiltrating lymphocytes) are grown ex vivo.
1986: U.S. Food and Drug Administration (FDA) approves interferon alfa.
1989: FDA approves erythropoietin.

1990s

New classifications of drugs (e.g., taxanes) are developed.


In clinical trials, paclitaxel is found to be effective against ovarian and breast cancers (Rowinsky et al., 1992).
FDA approves granulocytecolony-stimulating factor and granulocyte macrophagecolony-stimulating factor,
interleukin-2, interleukin-11, rituximab, trastuzumab, and denileukin diftitox.
Clinical trials of gene therapy and antiangiogenic agents begin.
FDA approves filgrastim for use in bone marrow transplantation and chemotherapy-induced neutropenia, severe chronic neutropenia, and peripheral blood stem cell transplantation.
FDA approves ondansetron for prevention of chemotherapy-induced nausea and vomiting; other 5-hydroxytryptamine-3 (5-HT3) receptor antagonists are in clinical trials (Perez, 1995).
As a result of improved symptom management, dose intensity becomes a focus.
FDA approves new analogs (e.g., vinorelbine) (Abeloff, 1995).
Scientists focus on the sequencing of agents (Bonadonna et al., 1995).
The genetic basis of cancers becomes an important factor in cancer risk research (e.g., BRCA1 for breast
cancer, renal cell cancer) (Gnarra et al., 1995; Hoskins et al., 1995; Miki et al., 1994).
Aromatase inhibitors are approved for breast cancer treatment. This marks a step forward for hormonal therapy.

2000present

The Childrens Oncology Group, a cooperative group combining the efforts of several groups, is formed to further the advancement of cancer treatment for children (www.childrensoncologygroup.org).
Scientists complete a working draft of the human genome (American Society of Clinical Oncology [ASCO],
n.d.).
Theory of immune surveillance continues, and biotherapy is used to target and mount a defense against certain antigens on malignant cells (e.g., gemtuzumab ozogamicin binds to CD33 on leukemic cells, rituximab
binds to CD20-positive non-Hodgkin lymphoma cells).
Radioimmunotherapy is used to deliver radioactivity directly to select tumor cells, avoiding damage to healthy
tissue (e.g., ibritumomab tiuxetan, tositumomab I-131).
FDA approves targeted therapies attacking epidermal growth factor receptor for lung cancer (gefitinib and erlotinib) and colon cancer (cetuximab and panitumumab) (ASCO, n.d.).
FDA approves antiangiogenic agents (bevacizumab was the first) (ASCO, n.d.).
Neurokinin-1 antagonist (aprepitant) is used in combination with other antiemetic drugs to prevent chemotherapy-induced nausea and vomiting.
Therapeutic vaccine trials are begun for existing cancers (e.g., OncoVAX, an autologous tumor cell vaccine,
is in phase III studies for stage II colon cancer), and FDA approves a prophylactic vaccine (Gardasil) for the
prevention of human papillomavirus infections that cause cervical cancer (ASCO, n.d.).
2010: Affordable Care Act is signed into law.

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Chapter 1. Overview of Cancer and Cancer Treatment

2. Surgery (Drake & Lynes, 2010; Gillespie, 2011)


a) Is a precise local treatment
b) May remove all or a portion of the primary tumor
c) Can be used to obtain specimens for cytopathology
d) May be the only treatment a patient requires
e) May be preceded or followed by other modalities
f) May be used in the palliative setting to alleviate or lessen intolerable symptoms
3. Radiation therapy (Gosselin, 2011; Kelvin, 2010)
a) Is a local treatment in which energy is precisely directed at a specific target
b) May follow surgery to prevent recurrence of the primary tumor
c) Is more effective for some diseases than others
d) Is sometimes used after chemotherapy because radiation can permanently damage bone marrow, making it impossible to give chemotherapy in the doses needed for curative therapy
e) Is often given in combination with chemotherapy (chemoradiation)
f) May be given as radioimmunotherapy (RIT), combining a radioisotope and a monoclonal antibody (mAb)
4. Chemotherapy/hormonal therapies (Levine, 2010; Tortorice, 2011)
a) Are systemic therapies, rather than local treatments, as drugs are distributed throughout the body by the bloodstream
b) May be used as single agents or, more commonly, in combination
c) Are limited by toxic effects on normal tissues
d) May have a tumoricidal effect in hormone-sensitive tumors because
of reduction or blockage of the source of the hormone or receptor
site where hormone is active
5. Biotherapy/targeted agents (Lapka & Franson, 2010)
a) Are systemic treatments
b) May modify the patients own immune defenses
c) May be so specific as to target a single receptor on the surface of tumor cells or an enzyme within the cell
d) May cause side effects and toxicities different from those of other antineoplastic agents
e) May be combined with other treatment modalities
f) May promote tumor regression
g) May stimulate hematopoiesis
D. Treatment approaches
1. Neoadjuvant therapy: The use of one or more treatment modalities prior to the primary therapy (e.g., chemotherapy before surgery). Goal is
to shrink the primary tumor to improve the effectiveness of surgery or
decrease the likelihood of micrometastases (Otto, 2007). In cases of locally advanced breast tumors, using neoadjuvant therapy may increase
the possibility for breast conservation.
2. Adjuvant therapy: Therapy following the primary treatment modality
(e.g., chemotherapy or radiation after surgery). The goal of adjuvant
therapy is to target minimal disease or micrometastases for patients at
high risk for recurrence (Otto, 2007).
3. Conditioning or preparative therapy: Administration of chemotherapy,
sometimes with total body irradiation, to eliminate residual disease or
empty the marrow space prior to receiving a stem cell transplant (also
referred to as myeloablation).
a) Myeloablation: Obliteration of bone marrow with chemotherapeutic
agents typically administered in high doses in preparation for peripheral blood stem cell or bone marrow transplantation (BMT). Myeloablative therapy does not allow for spontaneous marrow recovery because
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

of the lethal doses of agents used; therefore, it must be followed by


stem cell transplantation to prevent death. An example of myeloablative therapy is cyclophosphamide plus total body irradiation or busulfan plus cyclophosphamide (National Marrow Donor Program, 2012).
b) Nonmyeloablative: Reduced-intensity conditioning using doses that
are not lethal to bone marrow (Poliquin, 2007). Use of nonmyeloablative regimens has expanded the number of patients eligible for transplantation (National Marrow Donor Program, 2012).
4. Immunosuppression: Administration of chemotherapy at doses sufficient to blunt a patients immune response. This is done prior to transplantation to prevent graft rejection in allogeneic stem cell transplant
recipients. Agents such as methotrexate are given post-transplantation
to prevent graft-versus-host disease (GVHD). Certain agents are given
for immunosuppression to treat noncancerous conditions, such as autoimmune diseases.
E. Treatment strategies
1. Combination versus single-agent therapy (Tortorice, 2011): A combination of drugs is more effective in producing responses and prolonging life
than the same drugs used sequentially. With combination therapy, more
cancer cells are exposed in a sensitive phase, resulting in higher tumor
cell kill. Moreover, with rare exceptions, . . . single drugs at clinically tolerable doses have been unable to cure cancer (Chu & DeVita, 2013, p. 3).
a) Tumor cell populations are heterogeneous; therefore, a combination
of agents with different mechanisms of action is able to increase the
proportion of cells killed at any one time.
b) Combination agents with different mechanisms of action also reduce
the possibility of drug resistance, theoretically minimizing the chances for outgrowth of resistant clones (Skeel, 2011a).
c) Agents selected for use in combination chemotherapy have proven
efficacy as single agents.
d) Combination chemotherapy may use the principle of drug synergy to
maximize the effects of another drug. Synergy is affected by the rate of
tumor cell proliferation and by timing of drug administration (sequential or simultaneous; for example, leucovorin potentiates the cytotoxicity
of 5-fluorouracil [5-FU]) (Brown, in press). Combinations can be used
to provide access to sanctuary sites for reasons such as drug solubility
or affinity of specific tissues for a particular drug type (Skeel, 2011a).
e) Drugs with similar toxicities generally are avoided, although this is
not always possible. For example, both paclitaxel and cisplatin can
cause peripheral neuropathy as single agents but often are used together (Argyriou et al., 2007).
2. Dosing of chemotherapy
a) Treatment cycles are designed to permit recovery from damage to normal tissues and organs. Because the average white blood cell (WBC)
nadir is 1014 days, many regimens are based upon this time frame.
b) Administering a drug such as 5-FU at a steady concentration over a
period of time increases cell kill (Howland & Mycek, 2006).
c) Dose density refers to the drug dose per unit of time. Higher dose density is achieved by shortening the intervals between treatments (Freter,
2012). Reducing the time between chemotherapy cycles may diminish tumor regrowth. This strategy has resulted in longer survival for
patients with breast, ovarian, and colon cancers and lymphoma (Tortorice, 2011). The prophylactic use of the myeloid growth factor pegfilgrastim has allowed for administration of dose-dense chemotherapy regimens that would otherwise result in unacceptable neutropenia
(Burdette-Radoux et al., 2007; von Minckwitz et al., 2007).
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Chapter 1. Overview of Cancer and Cancer Treatment

d) Dose intensity is the amount of drug that is delivered over time. Nurses should be aware that dose reduction or delay resulting from chemotherapy side effects, scheduling conflicts, or any other reason reduces dose intensity and may negatively affect patient survival (Tortorice, 2011). Optimal cell kill is achieved by delivering sufficient doses of chemotherapy at planned intervals.
e) Relative dose intensity is calculated by comparing the received dose
to the planned dose of the standard regimen. Proactively managing
symptoms and educating patients on the importance of maintaining
the prescribed dosing schedule are paramount. (See Chapter 7 for
further discussion of dosing concepts.)
F. Goals of cancer therapy: Treatment planning includes discussion with patients about their goals of therapy and whether those goals are realistic
(Skeel, 2011b).
1. Prevention (Mahon, 2010)
a) Primary cancer prevention: Measures taken to avoid carcinogen exposure and promote health. Steps taken to prevent disease development
(e.g., avoidance of tobacco products, immunization against HPV).
(1) Chemoprevention: The use of selected pharmacologic agents
to prevent cancer in high-risk individuals, such as the administration of tamoxifen to women whose personal health history
indicates they are at a statistically increased risk for developing
breast cancer (Brown, in press).
(2) There has been discussion related to the role of nutritional epidemiology in the identification of nutritional or chemopreventive approaches to colon cancer, but that has yet to be confirmed (Marshall, 2009).
b) Secondary cancer prevention: Early detection and treatment of cancer
c) Tertiary cancer prevention: Monitoring for and/or preventing recurrence of the original cancer or secondary malignancies
2. Cure: Defined as the prolonged absence of detectable disease. This is the
desired outcome for all patients but is not always achievable.
3. Control: When cure is not possible, the goal is to allow patients to live
longer than if therapy had not been given (Skeel, 2011b). Treatment
often extends life and may prevent the growth of cancer cells without
complete elimination of disease or may reduce existing disease (Gosselin, 2011).
4. Palliation: Palliative cancer care is the integration of therapies that address the multiple issues that cause suffering in patients with cancer
and their families. In 2009, the American Society of Clinical Oncology
(ASCO) Board of Directors advocated that palliative care be offered to
all patients from the time of diagnosis to death (Ferris et al., 2009). Palliation involves reduction of side effects and symptoms, including pain
(Brown, in press; Gaddis & Gullatte, in press). It may include surgery,
radiation therapy, chemotherapy, or biotherapy, individually or in combination (Otto, 2007).
G. Measuring response
1. Measuring tumor response
a) Objective tumor response is assessed through a quantitative measurement such as surgical examination, imaging studies, or serum
tumor markers. Measurements recorded at the time of diagnosis are
compared to those recorded after treatment completion. In 1981,
the World Health Organization (WHO) first published tumor response criteria with overall assessment of tumor burden. Response
to therapy may be measured by survival, disease-free survival, obCopyright 2014 by the Oncology Nursing Society. All rights reserved.

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

jective change in tumor size or in tumor product, and subjective


change (Skeel, 2011a). With neoadjuvant therapy, tumor response
and resectability are partial determinants of effectiveness (Skeel,
2011a). The current end point for assessing response to therapy in
solid tumors is measuring change in tumor size (Kumar, Halanaik,
& Dahiya, 2010).
b) Tumor response has historically been classified using the following
system (Wahl, Jacene, Kasamon, & Lodge, 2009).
(1) Complete response: Absence of all signs and symptoms of cancer for at least one month using objective criteria (e.g., quantitative bidimensional tumor measurement)
(2) Partial response: At least a 50% reduction of measurable tumor mass for one month without development of new tumors
(3) Stable disease: A reduction in tumor mass of less than 50% or
less than a 25% increase in tumor growth
(4) Progressive disease: Growth of 25% or more or development of
new tumors. Note that this definition of progressive is negative,
in contrast to the standard English usage of the term.
(5) Relapse: After complete response, a new tumor appears or the
original tumor reappears. Following partial response, a new tumor appears or the original tumor increases in size. See Table
2 for further information.
c) Response Evaluation Criteria in Solid Tumors (RECIST) guidelines
were developed in 1999 by an international task force including
the European Organization for Research and Treatment of Cancer
(EORTC), NCI, and the National Cancer Institute of Canada Clinical Trials Group. The criteria were revised in 2008 and notated as
RECIST 1.1.
(1) Guidelines are intended to facilitate communication between researchers and clinicians (Therasse, Eisenhauer, & Buyse, 2006).
(2) Considerable variation exists between the original RECIST and
WHO criteria for evaluating response (Mazumdar, Smith, &
Schwartz, 2004; Schwartz et al., 2006), as well as subsequent editions of RECIST. These variations create a challenge for evaluating the effectiveness of therapies being studied in clinical trials. For example, RECIST criteria may show tumor progression
more slowly than WHO criteria, and RECIST 1.1 criteria result
in a higher complete response rate than the original RECIST
criteria (Wahl et al., 2009).
2. WHO (Therasse et al., 2000) recognizes that diagnostic technologies
(e.g., computed tomography [CT] scans, magnetic resonance imaging
Table 2. Comparison of WHO and RECIST Criteria for Tumor Response
Response

WHO

RECIST 1.1

Complete response

Absence of all known disease for at least 4


weeks

Disappearance of all target lesions

Partial response

50% reduction of measurable tumor mass for


4 weeks without development of new tumors

30% reduction in the sum of the diameters of target lesions compared to the baseline

Progressive disease

Growth of 25% or more, or development of


new tumors

20% increase in the sum of diameters of target lesions

Stable disease

Unable to meet criteria for either partial response or progressive disease

Unable to meet criteria for either partial response or


progressive disease

RECISTResponse Evaluation Criteria in Solid Tumors; WHOWorld Health Organization


Note. Based on information from Eisenhauer et al., 2009; Wahl et al., 2009.
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Chapter 1. Overview of Cancer and Cancer Treatment

[MRI]) have led to confusion regarding three-dimensional measurement


of disease. As a result, the reported response criteria vary among research
groups. See Table 2 for a comparison of WHO and RECIST criteria.
3. RECIST 1.1 guidelines
a) Response to a clinical trial is used to decide whether an agent or regimen demonstrated results promising enough to warrant further testing (prospective end point).
b) Baseline lesions are characterized as measurable or nonmeasurable.
At baseline, tumors must be measurable in at least one dimension
(using metrics) by calipers or a ruler. Baseline measurements must
be obtained within four weeks of initiating therapy. Lesions may be
measured using CT or MRI, but CT is preferred in most cases because
of variability in MRI scan parameters. In the original RECIST, nonmeasurable lesions included bone lesions, ascites, pleural or pericardial effusions, leptomeningeal disease, and inflammatory breast cancer. RECIST 1.1 now accepts bone metastases and soft tissue masses measuring 10 mm or larger as target lesions (Costelloe, Chuang,
Madewell, & Ueno, 2010).
c) The same method and technique used at baseline must be used to
evaluate response for reporting and follow-up.
d) If the primary end point is response to treatment, the patient must
have at least one measurable lesion at baseline. If only one measurable lesion is present, it must be confirmed by cytology or histology.
e) Measurable lesions, up to 5 per organ or 10 in total, are identified
as target lesions.
(1) Lesions selected are the longest in diameter and suitable for
follow-up measurement.
(2) The sum of the longest diameters for all target lesions is designated as the baseline sum longest diameter. This sum is used as the
reference to compare response (Skeel, 2011b).
(3) All other nontarget lesions are measured and recorded if possible. Their presence or absence can be noted for follow-up but
is not included in the response evaluation. For example, effusions cannot be measured, nor can lesions with necrotic centers (Skeel, 2011b).
f) Using RECIST criteria: See Table 2.
(1) Time to progression is a valuable indicator in cases when treatment results in disease stability despite failure to produce measurable shrinkage. This can be used as an indicator of disease status
when there is no measurable disease at the start of therapy, given the limitations of current RECIST 1.1 criteria (Skeel, 2011b).
(2) Follow-up should be protocol specific.
(a) Every other cycle (six to eight weeks) is reasonable for follow-up.
(b) Patients who discontinue therapy because of deterioration
of their health condition without evidence of progressive
disease are identified as symptomatically deteriorated and not
included in the partial response, stable disease, or progressive disease groups.
(c) At the conclusion of treatment, follow-up tests and schedules
are based on the goal of the study. If time to a specific event,
such as recurrence or death, is the primary end point of the
study, measurements must be compared to the baseline.
(d) The duration of overall response is measured from when
the measurement criteria were met for complete or partial response until the first date a recurrence or progressive disease was measured.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

10

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(e) The duration of stable disease is the time from initiation of


therapy until the criteria are met for progressive disease.
g) Reporting using RECIST 1.1 results: All patients in a study are assessed at the end of the study. Patients are assigned to one of the following categories.
(1) Complete response
(2) Partial response
(3) Stable disease
(4) Progressive disease
(5) Early death from disease
(6) Early death from toxicity
4. Glucose analog tracer, fluorine-18 fluorodeoxyglucose (18F-FDG),
positron-emission tomography (PET) scans: Used to assess tumor response both qualitatively and quantitatively (Costelloe et al., 2010)
with PERCIST (Positron Emission Tomography Response Criteria in
Solid Tumors).
a) Used to capture and report fractional change in standardized uptake value at intervals during and after treatment (Wahl et al., 2009)
b) 18F-FDG PET scans have lower sensitivity and specificity for non-small
cell lung cancer than previously published (Levitan, 2012).
5. MDA (University of Texas MD Anderson Cancer Center) classification:
Uses key imaging techniques to stratify patients with breast cancer with
bone-only metastases with respect to progression-free survival, overall
survival, and clinical response. Use of this classification may enable bone
lesions to be considered measurable disease (Hamaoka et al., 2010).
6. Measuring patient response: Performance status scales are used as part
of inclusion and exclusion criteria for clinical trials (Vogel, 2011). Table
3 compares three commonly used performance status scales.
a) Karnofsky Performance Status (KPS) scale: Evaluates adult performance in terms of percentage; a lower score indicates poorer performance (Karnofsky & Burchenal, 1949).
b) Eastern Cooperative Oncology Group (ECOG) and Zubrod scales:
Evaluate adult performance on a 05 scale; a higher score indicates
poorer performance (Oken et al., 1982).
c) WHO scale: Developed by the United Nations and includes performance and toxicity grading.
d) Lansky Performance Scale: Developed specifically for use in children,
as the KPS scale often is not applicable in pediatric populations (Lansky, List, Lansky, Ritter-Sterr, & Miller, 1987).
e) Quality of life (QOL): A partially independent measure of performance determined based on the patients own perceptions. It has
been shown to be an independent predictor of tumor response and
survival in some cancers (Skeel, 2011a).
H. Factors affecting treatment response
1. Pretreatment comorbidities and performance status: Patients with comorbid conditions and those who have been heavily pretreated may be
less able to tolerate the side effects and toxicities of chemotherapy, thus
affecting dose intensity and treatment planning (Camp-Sorrell, 2011).
After tumor type, performance status or activity level is the most important factor to consider when determining appropriate and tolerable
treatment. Patients who have poorer performance scores (e.g., bedridden) may be unable to withstand the rigors of an aggressive treatment
regimen and may experience decreased QOL. Patients who are fully active or have mild symptoms respond more frequently to treatment and
survive longer than those who are less active or experience more symptoms (Skeel, 2011b).
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 1. Overview of Cancer and Cancer Treatment

11

2. Tumor burden: The inverse relationship between the number of tumor cells and response implies that the smaller the tumor, the higher
the rate of response (Tortorice, 2011). As tumor mass increases, the
growth rate slows, decreasing the effectiveness of antineoplastic therapy. Additionally, large solid tumors may have inadequate blood flow,
which inhibits the ability of the chemotherapy to reach the entire tumor (Tortorice, 2011).
3. Rate of tumor growth: Tumor doubling time (time for the tumor to double in mass) and growth fraction (proportion of proliferating cells in relation to the total number of tumor cells) are important factors affecting

Table 3. Performance Status Scales


The Karnofsky Performance Status scale has been used in oncology, hospice, case management, and other healthcare settings since
1949. It is a tool for classifying patients on a scale from 0 to 100 according to their level of functional impairment. The Karnofsky scale is
designed for patients age 16 and older.
Rating

Description

100

Normal; no complaints; no evidence of disease

90

Able to carry on normal activity; minor signs or symptoms of disease

80

Able to carry on normal activity with effort; some signs or symptoms of disease

70

Cares for self; unable to carry on normal activity or do active work

60

Requires occasional assistance but able to care for most personal needs

50

Requires considerable assistance and frequent medical care

40

Disabled; requires special care and assistance

30

Severely disabled; hospital admission indicated although death not imminent

20

Very sick; hospital admission necessary; active supportive treatment necessary

10

Moribund; fatal processes progressing rapidly

Dead

The Eastern Cooperative Oncology Group, World Health Organization, and Zubrod Performance Status scales also are used to classify
patient responses to treatment. These scales are designed for patients age 16 and older.
Grade

Description

Fully active; able to carry on all predisease performance without restriction

Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g.,
light housework, office work)

Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours

Capable of only limited self-care; confined to bed or chair more than 50% of waking hours

Completely disabled; cannot carry on any self-care; totally confined to bed or chair

Dead

The Lansky Performance Scale is used to classify pediatric patients (younger than 16 years old) according to functionality.
Score

Description

100

Fully active

90

Minor restriction in physically strenuous play

80

Restricted in strenuous play; tires more easily, otherwise active

70

Both greater restrictions of and less time spent in active play

60

Ambulatory up to 50% of time; limited active play with assistance/supervision

50

Considerable assistance required for any active play; fully able to engage in quiet play

40

Able to initiate quiet activities

30

Needs considerable assistance for quiet activity

20

Limited to very passive activity initiated by others (e.g., watching TV)

10

Completely disabled, not even passive play

Note. Based on information from National Marrow Donor Program & Medical College of Wisconsin, 2009; Skeel, 2011b.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

12

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

response. Cytotoxic chemotherapy agents are most effective if given during the growth phase of the tumor, when a high percentage of cells are
susceptible to the effects of that agent (Skeel, 2011a; Tortorice, 2011).
4. Hormone receptor status
a) Presence of estrogen receptors (ERs) and/or progesterone receptors
(PRs) is prognostic for breast cancer. Patients who are ER/PR positive demonstrate better overall survival rates (Yackzan, 2011). Tumors
that grow more rapidly in the presence of a specific hormone may be
suppressed with an antihormonal agent.
b) Hormone receptor status has become increasingly important in cancer therapy.
5. Drug resistance: Many patients experience relapse because tumors become resistant to the drugs used to treat them (McDermott, Downing,
& Stratton, 2011).
a) Genetic instability of tumor cells and the emergence of drug resistance are currently considered the most significant determinants of
tumor response to treatment (Tortorice, 2011).
b) Complex biochemical pathways involving a multitude of receptors
and enzymes are implicated and depend upon the type of cell and
chemotherapy agent (Tortorice, 2011).
c) Research points to a complex interaction among cytotoxic agents,
chemical messengers (transporters that deliver drugs to the tumor),
and the genetic ability of malignant cells to avoid chemotherapyinduced apoptosis because of their high rate of genetic instability
(Gaddis & Gullatte, in press; Tortorice, 2011).
d) Genomic changes, originally presenting in small subclones of cancer cells, often underlie acquired resistance, such as ABL mutation
in chronic myeloid leukemia and MET in non-small cell lung cancer.
Genomic differences have an important role in determining how a
given cancer will respond to treatment (McDermott et al., 2011).
e) Tumor cells may be inherently resistant to antineoplastic agents or develop resistance after drug exposure because of the emergence of resistant clones. Single-agent resistance or multidrug resistance (MDR)
can occur and may be caused by a number of factors.
(1) Insufficient dosing may lead to the development of resistant
cell clones arising from random mutations in cellular DNA.
(2) Chemotherapy may kill sensitive cells while sparing cells resistant to treatment administered (Tortorice, 2011).
(3) MDR occurs when malignant cells are exposed to cytotoxic agents
possessing dissimilar mechanisms of action and appears to be
caused by mutations in the malignant cells regulatory system
(Tortorice, 2011). Several pathways are thought to be responsible for MDR, including alterations in the metabolism of chemotherapy within the tumor, the ability of tumor cells to repair
damaged DNA (thus bypassing apoptosis), and decreased uptake by formerly susceptible cells (Tortorice, 2011). MDR pathways include the following.
(a) Overexpression of the MDR1 gene, which encodes for the
cell membrane efflux pump P-glycoprotein (P-gp), is believed to cause resistance by its ability to remove toxic molecules (e.g., chemotherapy) from inside the cell before the
drug can reach the DNA. The presence of P-gp is a poor
prognostic indicator (Gonzalez-Angulo et al., 2007; Tortorice, 2011).
(b) Resistance to topoisomerase drugs (e.g., doxorubicin) can occur when the tumor develops the ability to change the binding properties of topoisomerase enzymes (Tortorice, 2011).
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 1. Overview of Cancer and Cancer Treatment

(c) MDR can occur from increased levels of normally protective enzymes (e.g., glutathione S-transferase), which facilitate the elimination of platinum compounds and alkylating agents from malignant cells (Tortorice, 2011).
(4) Impaired metabolism may result in reduced drug activation or
increased drug deactivation.
(5) Other types of resistance
(a) Acquired resistance is the result of further mutations after exposure to additional drugs and nongenetic mechanisms (Lackner, Wilson, & Settleman, 2012). KRAS mutations contribute to the acquired resistance of colorectal cancers treated with agents targeted against epidermal
growth factor receptor (EGFR). KRAS mutations account
for 40%50% of relapses among patients with colorectal
cancers (Azvolinsky, 2012).
(b) Emergent resistance occurs after the affected cells survive an
exposure to an environmental carcinogen (e.g., tobacco).
(c) Cells may be temporarily less responsive because of changes in environment or stimuli or may have permanent resistance (Freter & Goldie, 2012).
(d) Poor blood supply to the tumor may cause temporary resistance, which prevents delivery of a therapeutic dose of
drug (Tortorice, 2011).
(6) Overcoming drug resistance remains a high priority. Recurrences are presumably attributed to the inability to assess which tumors are resistant to treatment when administering in an adjuvant setting (Dawood et al., 2008). Researchers continue to
look for ways to deactivate P-gp in malignant cells and to identify new agents that alter the apoptotic pathways, increase the
effectiveness of current chemotherapy, and interact with specific characteristics associated with the DNA in malignant cells
(Barton-Burke & Wilkes, 2006).

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)
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Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 2

Drug Development and


Clinical Trials
A. Development of new cytotoxic and other therapeutic agents: Although there
is a sense of urgency to develop new and better therapies, protection of the
public is paramount. Steps to develop new anticancer agents are complex,
as well as time and resource consuming. NCI, a division of the National Institutes of Health (NIH), examines thousands of agents each year to discover new ones for testing. Only a small percentage are selected for preclinical testing, and even fewer are tested in phase I clinical trials (see Table 4).
1. Preclinical studies: Laboratory research using animal models often is
conducted collaboratively by NCI and pharmaceutical companies. The
NCI Cancer Therapy Evaluation Program (CTEP) seeks pharmaceutical sponsorship early once an agent is discovered because NCI does not
market new agents. Pharmaceutical companies may seek CTEP codevelopment (Humphrey et al., 2011).
2. Preclinical studies involve laboratory analysis and animal subjects; they
do not involve human subjects (Wong, Bales, & Hurtado, in press).
a) Scientists undertake empirical or rational research to develop a new
agent or a derivative of an existing agent that is more effective, has
fewer side effects, or is less toxic than existing agents.
b) The new agent is tested in vitro in various tumor cell lines. If the agent
is effective, scientists perform in vivo testing using mice or other research animals.
c) The agent is tested for stability, solubility, and dose.
d) Scientists perform studies involving animals to predict the initial dose
for use in human studies.
B. Clinical trials involving humans: The purpose of a clinical trial is to study a
new agent, combination of agents, or device by involving human volunteers
in a scientific experiment. Scientists evaluate the safety, effectiveness, and
toxicities of a new drug or drug combination in humans. Clinical trials are
vital to improving patient care and reducing cancer morbidity and mortality. However, only about 3% of adults with cancer enroll in clinical trials (Institute of Medicine, 2010). Nurses can have a positive impact on this number by being knowledgeable about clinical trials, assisting with patient education, and recording careful documentation of patient symptoms and care
(Deininger, 2010).
1. Regulatory entities relevant to the protection of human research subjects: In addition to strict federal regulation, multiple regulatory groups
oversee the participation of individuals in research (DeLaCruz &
McCabe, 2011).
a) The Office for Human Research Protections (OHRP) operates within the DHHS and oversees the development of informed consent
(IC) documents, the formation and function of institutional review
boards (IRBs), and safeguarding the welfare of research participants.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Table 4. Overview of Phases of Clinical Trials


Phase

Description

Goals

Subjects

Study Design

Exploratory study using


small doses of investigational agent (i.e., microdosing for a drug or biologic)
Very limited drug exposure
with limited duration of
dosing ( 7 days)
No therapeutic (or diagnostic) intent
Conducted prior to traditional phase 1 study
Conducted under an exploratory Investigational
New Drug application

Provide human pharmacokinetic/pharmacodynamic


data prior to definitive phase
12 testing.
Determine whether mechanism of action defined in preclinical models can be observed in humans.
Refine biomarker assay using human tumor tissue and/
or surrogate tissue.
Enhance efficiency of subsequent development of the
agent.
Increase chance of success
of subsequent development
of the agent.

Limited number (~10


12)

Dose escalation
Open-label
Nonrandomized

Traditional first-in-human
dose-finding study for single agent
Dose-finding study when
using multiple agents or
multiple interventions
(e.g., drug plus radiation)

Evaluate the safety and tolerability.


Determine the maximum tolerated dose.
Single agent
Combination of agents
Combination interventions
Determine dose-limiting toxicity.
Define optimal biologically
active dose.
Evaluate pharmacokinetics/
pharmacodynamics.
Observe preliminary response (e.g., antitumor activity).

Limited number (20


100)
Healthy volunteers
Patient volunteers
Usually includes many
cancer types (e.g., solid tumors)
Refractory to standard
therapy or no remaining
standard therapy
Adequate organ function, specifically bone
marrow, liver, and kidney
Pediatric studies conducted after safety and
toxicity evaluation in
adults

Dose escalation
Traditional 3 + 3
Accelerated titration
Adaptive
Open-label
Randomized (healthy
volunteers)
Nonrandomized (patient
volunteers)

II

Phase IIA: Proof-of-concept


study to provide initial information on activity of intervention to justify conducting a larger study
Phase IIB: Optimal dosing
study to target population

Phase IIA
Demonstrate activity of the
intervention in the intended patient condition/targeted population.
Establish proof of concept.
Phase IIB: Establish optimal
dosing for the intended patient condition/targeted population to be used in phase
III study.
Evaluate for safety.

Moderate number (80


300)
More homogenous population that is deemed
likely to respond based
on
Phase I data
Preclinical models
Mechanisms of action
Requires disease that
can be accurately measured and must be reproducible
May limit number of prior treatments

Open-label or blinded
Nonrandomized or randomized
One-stage, two-stage,
or crossover
Nonstratified or stratified

III

Randomized controlled
study

Compare efficacy of intervention being studied to a control group.


Evaluate for safety.

Large number (hundreds to thousands)


Homogenous population
May be used for initial
treatment

Open-label or blinded
Randomized
Nonstratified or stratified
Multi-institution/multisite

(Continued on next page)


Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 2. Drug Development and Clinical Trials

19

Table 4. Overview of Phases of Clinical Trials (Continued)


Phase
IV

Description
Postmarketing

Goals

Subjects

Study Design

Evaluate safety during postmarketing period.


May or may not be required
by the U.S. Food and Drug
Administration.
Compare the drug to another
similar product that is already
being marketed.
Monitor for long-term effects
and additional safety, efficacy, and quality-of-life data.
Assess drug-food interactions.
Assess effect in specific populations (e.g., pregnant women, children), or determine
cost-effectiveness.

Large number of subjects with the labeled indication of the newly


marketed drug/biologic

Open-label
Multi-institution/multisite

Note. Based on information from Doroshow & Kummar, 2009; Kummar et al., 2006; Lertora & Vanevski, 2012.
From Types of Research: Experimental, by E. Ness and G. Cusack in A.D. Klimaszewski, M.A. Bacon, J.A. Eggert, E. Ness, J.G. Westendorp, and K. Willenberg (Eds.), Manual for Clinical Trials Nursing (3rd ed.), in press, Pittsburgh, PA: Oncology Nursing Society. Copyright by the Oncology Nursing Society.
Reprinted with permission.

b) The U.S. Food and Drug Administration (FDA) regulates clinical trials that involve the licensing of a drug or product regardless of the
source of research funding.
c) IRBs are institutionally based and assess clinical trials for risks, benefits, and ethical status and monitor the overall conduct of the clinical trial. NCI sponsors a Central IRB Initiative in consultation with
OHRP. This initiative was designed to decrease the administrative
burden on local IRBs and investigators. Information on the Central
IRB Initiative can be found at www.ncicirb.org.
d) A data monitoring committee is required for all phase III trials. The
purpose of this independent group of experts is to protect the safety of trial participants, the credibility of the study, and the validity of
study results. The committee may recommend termination of a study
if appropriate (Bales & Adams, in press).
2. Drug approval process
a) Research protocols are designed within an academic environment,
through NCI, by pharmaceutical companies, or by cooperative research groups. Funding may originate from public or private sources.
b) If a trial involves a new agent, the FDA reviews and approves the agent
as an Investigational New Drug, or IND.
c) Table 4 presents an overview of the phases of clinical trials (Ness &
Cusack, in press).
d) The FDA approves a new drug for commercial use when studies have
documented its efficacy and safety.
e) The drug is marketed commercially.
f) Postmarketing studies are conducted to define new uses for approved
drugs and monitor for toxicities, long-term safety, and long-term effectiveness (Ness & Cusack, in press).
3. Pediatric patient involvement in clinical trials
a) More than 90% of pediatric patients with cancer receive treatment
at centers affiliated with a multi-institution collaborative research
group, such as the COG. Approximately 60% of children with cancer are treated in a COG protocol (COG, n.d.).
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

20

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

b) In general, new drugs are tested in adults before researchers undertake studies involving children.
c) Because childrens size and metabolism differ significantly from those
of adults, drug data derived from adults may not apply to children.
4. Nurses roles in clinical trials: Nurses may
a) Help patients find clinical trials. Useful resources include (Deininger,
2010)
(1) NIHs Clinical Trials website (http://clinicaltrials.gov), which
lists clinical trials and provides education about clinical trials
for consumers
(2) NCIs Cancer Trials Support Unit (www.ctsu.org), which focuses on phase III clinical trials
(3) Coalition of National Cancer Cooperative Groups TrialCheck
(www.trialcheck.org/services), which focuses on cooperative
group oncology trials
(4) Pharmaceutical company registry websites, such as GlaxoSmithKline (www.gsk-clinicalstudyregister.com) and Eli Lilly (www
.lillytrials.com/initiated/initiated.html)
(5) Internationally, nationally, and locally developed and maintained registries.
b) Support prospective participants as they decide whether to enroll.
When patients are considering participation in a clinical trial, they
may be facing other stressors in addition to the enrollment decision,
including a new diagnosis of cancer, disease progression, financial
concerns, psychosocial distress, disruption of career, and role changes at home. Nurses can help by screening for psychological distress at
every visit and referring patients to social work, pastoral care, or mental health services as appropriate (Czaplicki, in press).
c) Ensure IC when patients decide to participate.
(1) IC is a heavily regulated process to protect human rights, of
which the IC document is only a part (Klimaszewski, in press).
Table 5 delineates the steps in the IC process. Nurses are involved in this process by
(a) Ensuring that patients and/or family members understand
the purpose of participation in the clinical trial and allowing adequate time for them to receive answers to all of their
questions. This involves arranging for time with the clinical investigator and/or clinical trials nurse.
(b) Providing educational materials as required. All materials
presented to patients and families must be language specific, developmentally appropriate, and accurate.
(c) Documenting that patients understand the clinical trial,
follow-up and test schedules, and their right to withdraw
at any time (Klimaszewski, in press).
(2) The institutions IRB reviews and revises the IC document for format and appropriateness of reading level for the patient and family. NCI provides a consent form template for adult cancer trials
(see www.cancer.gov/clinicaltrials/conducting/simplification
-of-informed-consent-docs/page3). OHRP and FDA regulations
about the IC document are found in the Code of Federal Regulations and may be viewed at www.hhs.gov/ohrp/humansubjects/
guidance/45cfr46.html#46.116. A basic consent document must
(U.S. DHHS, 2010)
(a) State that the study involves research, provide an explanation of the purpose of the research, identify the possible
duration of the subjects participation, and describe the
procedure(s).
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 2. Drug Development and Clinical Trials

21

Table 5. The Informed Consent Process


Step

Key Elements

Initial meeting

Provide subject and family/friends with the informed consent form (CF).
Discuss the CF logically with subject and one or more members of the research team.
Encourage subject and family to take notes.
Provide adequate time for subject and family members to consider participation and have all questions answered.
Provide subject with a video, audiotape, or interactive computer program to help him or her to understand the information in the CF.
Parents will represent subjects younger than age 18.
If subject is between age 7 and 18, ask for assent to participate, and provide an assent form for signature.

Time to read and


consider participation

Subject is afforded adequate time to review the CF at his or her leisure.


Subject discusses the CF with family, friends, social workers, clergy, a subject representative, or other trusted advisers.
Subject records questions and concerns for discussion at next meeting.

Assessment of
understanding

Discuss subjects questions and concerns that were recorded at home.


Assess subjects understanding with interactive questioning, a written questionnaire, or by having the patient explain specific parts of the CF in his or her own words.
Document assessment of subjects understanding.
Answer subjects questions until the patient states that he or she has enough information to make a decision.
Document subjects statement regarding his or her decision.

Questions

Encourage subject to ask questions until the participant is satisfied with his or her understanding of the CF.
Encourage subject to record questions while away from the clinic and either bring them to the next meeting or
schedule a visit to have the questions discussed.

Verification before
treatment

Ask patient to verify that he or she still consents to the treatment he or she is about to receive immediately prior to
administering the treatment.

New information

Assure subject that any new information available will be shared.


Follow up on assurance.
Provide subject with an updated CF for signature (as required).
Document subjects understanding of new information in the presence of family.
Document subjects signing of the new CF, review of CF, and that all subjects questions were answered.
Provide copy of CF to subject.

Communication
techniques

Videotapes, audiotapes, interactive computer programs, discussions with qualified professional and lay individuals

Supplemental
materials

Videotapes, audiotapes, written materials, interactive computer programs

Note. Based on information from National Cancer Institute, 2013.


From Informed Consent, by A. Klimaszewski in A. Klimaszewski, M. Bacon, J.A. Eggert, E. Ness, J.G. Westendorp, and K. Willenberg (Eds.), Manual for
Clinical Trials Nursing (3rd ed.), in press, Pittsburgh, PA: Oncology Nursing Society. Copyright by the Oncology Nursing Society. Reprinted with permission.

(b) Describe foreseeable risks or discomforts that the participant might encounter.
(c) Describe benefits to the participant or to any others.
(d) Disclose appropriate alternative treatments that may be advantageous to the participant, if applicable.
(e) Describe how confidentiality of records that identify the
participant will be managed.
(f) Explain whether any compensation or other medical
treatments will be made available if injury occurs. If injury does occur, explain what medical treatments will
be available and where the participant can obtain further information.
(g) Clearly document for the participant contact information
for a person who will answer questions about the research
and whom to contact if the participant sustains a researchrelated illness or injury.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

22

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(h) State that the participant may discontinue involvement


in the trial at any time without penalty or loss of further
treatment(s) and that participation is voluntary.
(3) The nurse should ensure that the parents or a legally authorized representative of pediatric patients understand the concepts of consent, assent, and dissent as they relate to a childs
participation in research. While the parents/legally authorized
representative must provide consent, assent is a minors affirmative agreement to participate in research. Allowing assent
honors a minors autonomy to the extent that he or she has
developed the capacity to make informed choices. If a minor
does not object to participation, assent cannot be presumed
(Klimaszewski, in press). Dissent is a childs active refusal to
participate in research. NCI provides information on the assent process for care providers and parents and guardians (see
www.cancer.gov/clinicaltrials/learningabout/patientsafety/
childrensassent).
d) The Oncology Nursing Society (ONS) defined the role of oncology
clinical trials nurses through competencies (Daugherty, Schmieder,
Good, Leos, & Weiss, 2010) (see Table 6).
e) The oncology nurse caring for a patient on a study protocol has additional responsibilities depending upon the phase of the clinical trial,
such as performance and documentation of the following.
(1) Verify that the patient, parent, or legally authorized representative has given IC, that the original document is in the patients

Table 6. Oncology Clinical Trials Nurse Core Competencies


Competency

Description

I. Protocol
compliance

The oncology clinical trials nurse facilitates compliance with the requirements of the research protocol and
good clinical research practice while remaining cognizant of the needs of diverse patient populations.

II. Clinical trials


related communication

The oncology clinical trials nurse utilizes multiple communication methods to facilitate the effective conduct of
clinical trials.

III. Informed consent


process

The oncology clinical trials nurse demonstrates leadership in ensuring patient comprehension and safety during initial and ongoing clinical trial informed consent discussions.

IV. Management of
clinical trial patients

The oncology clinical trials nurse uses a variety of resources and strategies to manage the care of patients
participating in clinical trials, ensuring compliance with protocol procedures, assessments, and reporting requirements, as well as management of symptoms.

V. Documentation

The oncology clinical trials nurse provides leadership to the research team in ensuring collection of source
data and completion of documentation that validate the integrity of the conduct of the clinical trial.

VI. Patient
recruitment

The oncology clinical trials nurse utilizes a variety of strategies to enhance recruitment while being mindful of
the needs of diverse patient populations.

VII. Ethical issues

The oncology clinical trials nurse demonstrates leadership in ensuring adherence to ethical practices during the
conduct of clinical trials in order to protect the rights and well-being of patients and the collection of quality data.

VIII. Financial
implications

The oncology clinical trials nurse identifies the financial variables that affect research and supports good financial stewardship in clinical trials.

IX. Professional
development

The oncology clinical trials nurse takes responsibility for identifying his or her ongoing professional development needs and seeks resources and opportunities to meet those needs, such as through membership in
nursing, oncology, or research organizations.

Note. From Oncology Clinical Trials Nurse Competencies (pp. 1114), by P. Daugherty, L. Schmieder, M. Good, D. Leos, and P. Weiss, 2010, Pittsburgh, PA:
Oncology Nursing Society. Retrieved from http://www2.ons.org/media/ons/docs/publications/ctncompetencies.pdf. Copyright 2010 by the Oncology Nursing
Society. Reprinted with permission.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 2. Drug Development and Clinical Trials

medical record, and that the patient has received a copy before any study tests are performed or any study treatments are
administered.
(2) Clarify technical explanations of procedures and treatments.
(3) Obtain pretreatment assessment data.
(4) Measure height and weight, and check dose calculations with
a physician, pharmacist, or another qualified (i.e., chemotherapy-biotherapy trained) nurse.
(5) Have emergency medications and equipment available as appropriate.
(6) Instruct the patient to report changes or symptoms experienced
during and after drug administration.
(7) Assess the patients desire to continue by verbally affirming consent prior to beginning drug infusion (Klimaszewski, in press).
Patients have the right to withdraw at any time.
(8) Administer the drug(s) according to the protocol.
(9) Assess and evaluate drug reactions. Use the NCI Common
Terminology Criteria for Adverse Events (CTCAE), available
online (see http://ctep.cancer.gov/protocolDevelopment/
electronic_applications/ctc.htm) to assess individual toxicities
and identify trends in the study population.
(10) Follow up with telephone calls to assess the patient for delayed or chronic side effects as appropriate (Klimaszewski,
in press).
C. Expedited approval: The FDA may hasten the approval of new drugs to address an unmet medical need, provide a promising therapy to treat a serious condition, improve survival, or decrease toxicity of an accepted treatment. Termed Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review, these programs for expedited approval have potential benefits,
including (U.S. FDA, 2013)
1. Improved efficiency by promoting early communication between the
company submitting the drug and the FDA
2. Allowing submission of sections of the new drug application instead of
all components
3. Permitting the evaluation of various studies using surrogate end points
4. Providing priority review and accelerated approval of promising drugs.

References
Bales, C., & Adams, G. (in press). Data and safety monitoring plans. In A.D. Klimaszewski, M. Bacon,
J. Eggert, E. Ness, J.G. Westendorp, & K. Willenberg (Eds.), Manual for clinical trials nursing (3rd
ed.). Pittsburgh, PA: Oncology Nursing Society.
Childrens Oncology Group. (n.d.). What is a clinical trial? Retrieved from http://www
.childrensoncologygroup.org/index.php/what-is-a-clinical-trial
Czaplicki, K. (in press). Psychosocial distress. In A.D. Klimaszewski, M. Bacon, J. Eggert, E. Ness, J.G.
Westendorp, & K. Willenberg (Eds.), Manual for clinical trials nursing (3rd ed.). Pittsburgh, PA: Oncology Nursing Society.
Daugherty, P., Schmieder, L., Good, M., Leos, D., & Weiss, P. (2010). Oncology clinical trials
nurse competencies. Retrieved from http://www2.ons.org/media/ons/docs/publications/
ctncompetencies.pdf
Deininger, H.E. (2010). Clinical trials. In J. Eggert (Ed.), Cancer basics (pp. 287302). Pittsburgh, PA:
Oncology Nursing Society.
DeLaCruz, A., & McCabe, M.S. (2011). Principles of cancer clinical trials. In C.H. Yarbro, D. Wujcik,
& B.H. Gobel (Eds.), Cancer nursing: Principles and practice (7th ed., pp. 219231). Burlington, MA:
Jones and Bartlett.
Doroshow, J.H., & Kummar, S. (2009). Role of phase 0 trials in drug development. Future Medicinal
Chemistry, 1, 13751380. doi:10.4155/fmc.09.117
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

23

24

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)
Humphrey, R.W., Brockway-Lunardi, L.M., Bonk, D.T., Dohoney, K.M., Doroshow, J.H., Meech, S.J.,
Pardoll, D.M. (2011). Opportunities and challenges in the development of experimental drug combinations for cancer. Journal of the National Cancer Institute, 103, 12221226. doi:10.1093/jnci/djr246
Institute of Medicine. (2010). Transforming clinical research in the United States: Challenges and opportunities: Workshop summary. Washington, DC: National Academies Press. Retrieved from http://www
.ncbi.nlm.nih.gov/books/NBK50892/pdf/TOC.pdf
Klimaszewski, A.D. (in press). Informed consent. In A.D. Klimaszewski, M. Bacon, J. Eggert, E. Ness,
J.G. Westendorp, & K. Willenberg (Eds.), Manual for clinical trials nursing (3rd ed.). Pittsburgh,
PA: Oncology Nursing Society.
Kummar, S., Gutierrez, M., Doroshow, J.H., & Murgo, A.J. (2006). Drug development in oncology:
Classical cytotoxics and molecularly targeted agents. British Journal of Clinical Pharmacology, 62, 15
26. doi:10.1111/j.1365-2125.2006.02713.x
Lertora, J.J.L., & Vanevski, K.M. (2012). Clinical pharmacology and its role in pharmaceutical development. In J.I. Gallin & F.P. Ognibene (Eds.), Principles and practice of clinical research (3rd ed., pp.
627639). Boston, MA: Elsevier Academic Press. doi:10.1016/B978-0-12-382167-6.00043-6
National Cancer Institute. (2013). Simplification of informed consent documents: Appendix 4, communication methods. Retrieved from http://www.cancer.gov/clinicaltrials/conducting/simplification
-of-informed-consent-docs/page5#appendix4
Ness, E., & Cusack, G. (in press). Types of clinical research: Experimental. In A.D. Klimaszewski, M.
Bacon, J. Eggert, E. Ness, J.G. Westendorp, & K. Willenberg (Eds.), Manual for clinical trials nursing (3rd ed.). Pittsburgh, PA: Oncology Nursing Society.
U.S. Department of Health and Human Services. (2010). Title 45: Public welfare, Part 46: Protection
of human subjects, 46.116: General requirements for informed consent (45 C.F.R. 46.116). Retrieved from http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#46.116
U.S. Food and Drug Administration. (2013, June 26). Fast track, breakthrough therapy, accelerated approval and priority review: Expediting availability of new drugs for patients with serious conditions.
Retrieved from http://www.fda.gov/forconsumers/byaudience/forpatientadvocates/speeding
accesstoimportantnewtherapies/ucm128291.htm
Wong, S.F., Bales, C., & Hurtado, K. (in press). Investigational agents: Procurement, administration,
and accountability of research study drugs. In A.D. Klimaszewski, M. Bacon, J. Eggert, E. Ness, J.G.
Westendorp, & K. Willenberg (Eds.), Manual for clinical trials nursing (3rd ed.). Pittsburgh, PA: Oncology Nursing Society.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 3

Principles of Antineoplastic
Therapy
A. Life cycle of cells: The cell life cycle is a five-stage reproductive process occurring in both normal and malignant cells (see Figure 2) and propelled
by cyclincyclin-dependent kinase (CDK) complexes (Brown, in press; Malumbres, 2007; Otto, 2007; Williams & Stoeber, 2012).
1. Gap 0 (G0)
a) Resting or dormant phase
b) Cells are temporarily out of the cycle and not actively proliferating;
however, all other cellular activities occur.
c) Cells continue in G0 until there is a stimulus to enter the cell cycle.
d) Because they are not actively proliferating, cells in this phase have
some protection from exposure to cell cyclespecific chemotherapy agents.
2. Gap 1 (G1)
a) Postmitotic phase
b) Cells begin the first phase of reproduction and growth by synthesizing proteins and RNA necessary for cell division.
3. Synthesis (S): DNA is replicated.
4. Gap 2 (G2)
a) Premitotic (or postsynthetic) phase
b) The second phase of protein and RNA synthesis occurs.
c) Preparation for mitotic spindle formation occurs.
d) The cell is now prepared for division.
5. Mitosis (M)
a) Cell division occurs.
b) Shortest phase of the cell life cycle
c) At the conclusion of mitosis, two daughter cells result with exact copies of the parent cells DNA. Cells either reenter the cell cycle to reproduce or perform the specific functions of the tissue for which
they are programmed.
6. CyclinCDK complexes (Malumbres, 2007; Williams & Stoeber, 2012)
a) Cyclins are cell cycle kinase regulators (e.g., cyclin D).
b) CDKs are cell cycle kinase inhibitors (e.g., CDK4).
c) Cyclins and CDKs unite and create a complex that propels the cell
through each phase of the cell cycle (e.g., cyclin D-CDK4, cyclin DCDK6, and cyclin E-CDK2 drive G1).
d) CDK mutations have been linked to tumor formation (e.g., CDK6
is overexpressed in many hematologic malignancies, glioblastoma,
and lung cancer).
e) Anti-CDK/cyclin inhibitors are being developed and tested in clinical trials as a method to inhibit tumor growth.
B. Chemotherapeutic agents: Drugs are classified according to pharmacologic
action or their effect on cell reproduction (see Table 7).
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

25

26

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

1. Cell cyclespecific drugs exert effect within a specific phase of the cell
cycle (Brown, in press; Hande, 2009).
a) These drugs have the greatest tumor cell kill when given in divided but frequent doses or as a continuous infusion with a short cycle time. This allows the maximum number of cells to be exposed to
the drug at the specific time in their life cycle when they are vulnerable to the drug.
b) Classifications include antimetabolites, plant alkaloids (camptothecins, epipodophyllotoxins, taxanes, and vinca alkaloids), and miscellaneous agents.
2. Cell cyclenonspecific drugs exert effect in all phases of the cell cycle,
including the G0 (resting) phase (Brown, in press; Hande, 2009).

Figure 2. Cell Cycle

Growth Factors

G0
CDK
2,4,5,6

Resting Stage

Cyclin D

Active pRb
protein
(master
brake)

EARLY G1

Cell Division
Cyclins A,B
CDK1

G2

p53
p27
p21

Cyclin E CDK2

LATE G1

DNA
damage

TGF-

Proteins

S
Cyclin A
CDK2

Cyclin B
CDK1

DNA Synthesis

Cyclin B
CDK1

The cell cycle consists of 4 phases (G1, S, G2, M) that are controlled by proteins called cyclins. The cyclins (D, E, A, B) are activated when complexed with enzymes called cyclin-dependent kinases (CDKs). Upon activation, the cyclinCDK complex allows the cell
to progress through each specific cell cycle phase. Present throughout the cell cycle, the cyclinCDK complexes serve as checkpoints or monitors of the cell cycle. Inhibitory proteins prevent progression through the cell cycle if DNA damage is present or there
is a lack of nutrients or oxygen to support cellular proliferation. Examples of inhibitory proteins include p21, p27, p53. The inhibitory
proteins in turn are regulated by the presence of inhibitory growth factors and TGF-. Once past R (the restriction point) the cell cycle is turned on and progression through the cell cycle is inevitable. CyclinCDK complexes and pRB (the master brake) tightly
regulate the R point. The stability of the inhibitory proteins and cyclinCDK complexes are altered in cancer, thereby altering control
of the cell cycle, and uncontrolled cellular proliferation prevails.
Note. From Biology of Cancer (p. 14), by C.J. Merkle in C.H. Yarbro, D. Wujcik, and B.H. Gobel (Eds.), Cancer Nursing: Principles and Practice (7th
ed.), 2011, Burlington, MA: Jones and Bartlett. Copyright 2011 by Jones and Bartlett Publishers. Reprinted with permission.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 7. Characteristics of Chemotherapeutic Agents


Classification
Alkylating
agents

Mechanism
of Action
Break DNA helix
strand, thereby
interfering with
DNA replication

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

PO

Ovarian cancer

Dose-limiting toxicities: Neurotoxicity, peripheral neuropathy, myelosuppression


Nausea, vomiting, skin rash, hypersensitivity, elevation of LFTs, abdominal
cramps, diarrhea

Do not open capsules.


Monitor for progressive neurologic toxicity.
Instruct patients to take after meals and at bedtime.
(Eisai Inc., 2009)

Bendamustine
(Treanda)

IV

CLL, indolent
NHL

Dose-limiting toxicity: Myelosuppression


Pyrexia, nausea, vomiting, skin reactions

Infuse over 3060 min.


Monitor closely for infusion reactions (especially
in second or subsequent cycles).
Dose reduction or discontinuation may be necessary for hematologic toxicities.
Take precautions for TLS in high-risk patients.
Concomitant use of allopurinol may increase risk
of severe skin toxicity.
(Cephalon, Inc., 2012)

Busulfan (IV:
Busulfex;
oral: Myleran)

IV, PO

CML, BMT preparation

Dose-limiting toxicities: Myelosuppression, pulmonary fibrosis


Profound tachycardia, hypertension,
chest pain, hyperpigmentation, alopecia, sperm or ovarian suppression,
confusion, seizures, mucositis, nausea,
vomiting, insomnia, hyperglycemia,
blurred vision, second malignancy
Hepatic sinusoidal obstruction syndrome
(previously known as veno-occlusive
disease) has been reported in patients
receiving doses > 16 mg/kg in conjunction with alkylating agents for stem cell
transplant (Solimando, 2008).

Monitor blood counts closely. If leukocyte count is


< 20,000/mm3, discontinue drug.
Administer seizure prophylaxis.
Instruct patients to take on an empty stomach to
decrease risk of nausea and vomiting.
IV form should be administered through a central
line and has been associated with inflammation
and pain during infusion.
(PDL BioPharma, Inc., 2007)

Carboplatin
(Paraplatin)

IV

Ovarian cancer

Dose-limiting toxicity: Thrombocytopenia


Neutropenia (myelosuppression is
more pronounced with renal impairment), nausea, vomiting, hypersensitivity reaction, mild alopecia, skin
rash

Drug is an irritant.
Carboplatin exhibits much less renal toxicity than
cisplatin, so rigorous hydration is unnecessary
unless renal dysfunction exists.
Monitor blood counts closely, and reduce the
dose per protocol. Specific dosing guidelines
are recommended for carboplatin. See Figures
15, 16, and 17.
Give after taxanes in sequential regimens to limit
myelosuppression and enhance efficacy.

27

(Continued on next page)

Chapter 3. Principles of Antineoplastic Therapy

Altretamine
(Hexalen)

28

Table 7. Characteristics of Chemotherapeutic Agents (Continued)

Alkylating
agents (cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Carboplatin
(Paraplatin)
(cont.)

Nursing Considerations
Check creatinine level prior to each dose (for
AUC dosing).
Have emergency medications available for hypersensitivity reaction, which usually occurs after the seventh dose.
(Bristol-Myers Squibb Co., 2010a)

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chlorambucil
(Leukeran)

PO

CLL, HL, NHL

Dose-limiting toxicities: Myelosuppression, skin reactions


Ovarian or sperm suppression, nausea, vomiting, secondary malignancy, hyperuricemia, pulmonary fibrosis, seizure (increased risk in children
with nephrotic syndrome)

Use with caution in patients with seizure history


and within one month of radiation and/or cytotoxic therapy.
(GlaxoSmithKline, 2004)

Cisplatin
(Platinol)

IV

Ovarian, testicular, bladder, lung


cancer

Dose-limiting toxicities: Severe nephrotoxicity, myelosuppression


Severe acute and delayed nausea,
vomiting, ototoxicity (tinnitus and/or
high-frequency hearing loss are most
common), hyperuricemia, hypersensitivity reaction, hypomagnesemia and
other electrolyte abnormalities, peripheral neuropathy, SIADH

Cisplatin is an irritant with vesicant potential if >


20 ml of 0.5 mg/ml concentrated solution is extravasated.
Hold the drug if the patients SCr is > 1.5 mg/dl;
otherwise, irreversible renal tubular damage
may occur (Aronoff et al., 2007). Amifostine
may be used as a renal protectant. Rigorous
hydration is necessary to prevent nephrotoxicity. Use mannitol to achieve osmotic diuresis.
Potential exists for delayed nausea and vomiting
up to 6 days after administration.
Consider obtaining a baseline audiogram.
Monitor electrolytes and replace as needed.
(Bristol-Myers Squibb Co., 2010b)

Cyclophosphamide
(Cytoxan)

Intrapleural, IV,
PO

Breast and ovarian cancers, MM,


leukemias, lymphomas, neuroblastoma, retinoblastoma, mycosis fungoides

Dose-limiting toxicity: Hemorrhagic cystitis


Vomiting, myelosuppression, nausea,
alopecia, may cause a temporary
maxillary burning if administered too
quickly, secondary malignancy, testicular or ovarian failure
High-dose: acute cardiomyopathy,
SIADH

Give the dose, whether IV or PO, early in the day.


Ensure adequate hydration. If given PO, have patients drink 23 L/day (Solimando, 2008).
Have patients empty their bladder frequently
and before bed to prevent hemorrhagic cystitis.
Mesna may be considered in conjunction with
IV fluids for prevention of hemorrhagic cystitis.
Pelvic irradiation potentiates hemorrhagic cystitis.
When used with radiation therapy, potential for
radiation recall exists with subsequent doses of
cyclophosphamide.
(Baxter Healthcare Corp., 2013)
(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 7. Characteristics of Chemotherapeutic Agents (Continued)


Classification
Alkylating
agents (cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

IV

Malignant melanoma, HL

Dose-limiting toxicities: Severe neutropenia and thrombocytopenia (with


nadir at 23 weeks or more)
Severe nausea and vomiting for up to
12 hours, anorexia, alopecia, rash,
flu-like syndrome (fever, malaise, myalgias), hypotension, hypersensitivity
reaction (uncommon), photosensitivity, hepatic dysfunction

Dacarbazine is an irritant that may cause tissue necrosis if extravasated. Administer by infusion over 3060 min. May cause severe pain
and burning at the injection site and along the
course of the vein. To reduce these effects, increase the diluent, reduce the infusion rate,
and apply cold compresses to the needle insertion site and along the vein.
Protect solution from light (pink solution indicates
decomposition).
Flu-like syndrome may occur up to 7 days after
drug administration; treat symptoms.
Reduce doses for patients with poor renal function.
(Teva Parenteral Medicines, Inc., 2007)

Ifosfamide
(Ifex)

IV

Testicular cancer

Dose-limiting toxicities: Hemorrhagic


cystitis, myelosuppression
Nausea, alopecia, vomiting, neurotoxicity (somnolence, confusion, hallucinations, depressive psychoses, and encephalopathy)
Methylene blue has been used to treat
ifosfamide-induced encephalopathy;
reports have shown that the encephalopathy may spontaneously resolve
(Patel, 2006).

Administer the drug over 30 min or more.


To prevent hemorrhagic cystitis, always administer with mesna. Mesna may be given PO, as a
bolus dose, as a continuous infusion, or mixed
in the bag with the ifosfamide. Mesna dose
should be 60%100% of the ifosfamide dose
(based on weight). Refer to package insert for
specific dosing recommendations.
(Baxter Healthcare Corp., 2012)

Mechlorethamine (nitrogen mustard,


Mustargen)

IV

HL, NHL, CLL,


CML, mycosis
fungoides

Severe nausea, vomiting, alopecia, myelosuppression, pain or phlebitis at


IV site, chills, fever, testicular or ovarian failure

Drug is a vesicant.
Administer the agent over several minutes
through the side arm of a free-flowing IV. Flush
with 125150 ml NS post infusion.
If extravasation occurs, antidote is sodium thiosulfate. Use mechlorethamine as soon after
preparation as possible (1530 min); it is extremely unstable.
Do not mix mechlorethamine with any other drug.
(Baxter Oncology, 2012)

29

(Continued on next page)

Chapter 3. Principles of Antineoplastic Therapy

Dacarbazine
(DTIC)

30

Table 7. Characteristics of Chemotherapeutic Agents (Continued)

Alkylating
agents (cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Melphalan
(Alkeran)

IV, PO

MM, ovarian cancer

Dose-limiting toxicity: Myelosuppression


Nausea, vomiting, mucositis, hypersensitivity reaction

Myelosuppression may be delayed and last 46


weeks; monitor blood counts carefully. Hold or
reduce dose per institutional protocol.
Instruct patients to take on an empty stomach.
Application of ice chips to oral cavity is recommended during high-dose melphalan administration to prevent oral mucositis (Lilleby et al.,
2006).
Drug must be administered within 1 hour of reconstitution. Infuse over 1530 minutes.
(GlaxoSmithKline, 2011a)

Oxaliplatin
(Eloxatin)

IV

Colorectal cancer

Dose-limiting toxicities: Peripheral


neuropathy, myelosuppression
Acute primary transient peripheral sensory neuropathy that presents within
148 hours, resolves within 14 days,
and manifests as paresthesia, dysesthesia, or hypoesthesia in hands,
feet, oral cavity, and throat; can be
aggravated by cold temperatures
Anaphylactic reaction, nausea, vomiting, diarrhea, pulmonary fibrosis, fatigue, fever

Oxaliplatin has been described as an irritant and


a vesicant.
Consider dose reduction in patients with renal
dysfunction.
Monitor for acute, reversible effects and persistent neurotoxicity.
Avoid ice to oral cavity during oxaliplatin infusion.
For 34 days after therapy, patients should avoid
consuming cold drinks and foods and breathing
cold air (cover mouth with scarf).
Do not prepare or infuse in sodium chloride or
other chloride-containing solutions. D5W solution is recommended (Takimoto et al., 2007).
Flush after oxaliplatin with D5W before administering other medications in the same line.
Infuse after taxanes in sequential regimens.
Calcium and magnesium infusions may be used
during oxaliplatin therapy to reduce neurotoxicities (Wen, 2013).
However, in a trial that included 353 patients with
colon cancer undergoing adjuvant therapy with
FOLFOX (5-FU, oxaliplatin, and leucovorin),
patients were randomized to receive IV calcium and magnesium (1 g calcium gluconate, 1 g
magnesium sulfate) or placebo before and calcium and magnesium after oxaliplatin. In a third
arm in the trial, patients received calcium and
magnesium before and placebo after the oxaliplatin. The results showed no differences between the groups in either acute neurotoxicity
(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 7. Characteristics of Chemotherapeutic Agents (Continued)


Classification
Alkylating
agents (cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Oxaliplatin
(Eloxatin)
(cont.)
Temozolomide
(Temodar)

Nursing Considerations
or cumulative sensory neurotoxicity, as assessed both by patient and physician questionnaires (Loprinzi et al., 2013).
(sanofi-aventis U.S. LLC, 2011)

PO, IV

Refractory anaplastic astrocytoma, newly diagnosed glioblastoma multiforme

Dose-limiting toxicity: Myelosuppression


Nausea, vomiting, headache, fatigue,
liver toxicity, rash, alopecia

Do not open capsules.


Administer IV over 90 minutes.
Instruct patients to take on an empty stomach to
decrease risk of nausea and vomiting.
Do not administer if patients have had an allergic
reaction to dacarbazine.
Administer PCP prophylaxis with trimethoprimsulfamethoxazole in patients receiving with radiation therapy for 42-day regimen.
Take oral dose with a full glass of water.
Consider bedtime administration for oral dosing to decrease nausea and vomiting (Solimando, 2008).
(Merck & Co., Inc., 2013)

Thiotepa
(Thioplex)

IV, IT, intravesical, intratumoral

Dose-limiting toxicity: Myelosuppression


Hypersensitivity reaction, ovarian or
sperm suppression, nausea, vomiting, pain at infusion site, rash, fever, skin burn, mucositis, hemorrhagic cystitis

Thiotepa is primarily excreted in the urine; monitor renal function carefully.


Myelosuppression may be delayed (1428 days).
Thiotepa used in the transplant setting can
cause severe skin irritation. Frequent showering immediately following and during the first
24 hours after administration helps remove
the chemical from the skin. Additionally, avoid
tapes and skin adherents during and immediately following administration.
(Bedford Laboratories, 2001)

31

(Continued on next page)

Chapter 3. Principles of Antineoplastic Therapy

Bladder, breast,
and ovarian cancers, HL, NHL

32

Table 7. Characteristics of Chemotherapeutic Agents (Continued)

Antimetabolites

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Azacitidine is believed to cause


hypomethylation
of DNA and direct cytotoxicity
on abnormal hematopoietic cells
in the bone marrow. Abnormal
cells, including
cancer cells, no
longer respond
to normal growth
control mechanisms. The cytotoxic effects of
azacitidine cause
these cells to die,
whereas nonproliferating cells are
relatively insensitive to the medication.

Azacitidine
(Vidaza)

SC, IV

Patients with specific subtypes of


MDS

Dose-limiting toxicities: Myelosuppression, elevated SCr, renal failure


Nausea, vomiting, diarrhea, fatigue, fever, erythema at injection site, hypokalemia, renal tubular acidosis, hepatic coma, constipation

IV: Mix in 50100 ml NS or LR only. Infuse over


1040 min. Administration should be completed
within 1 hour of reconstitution.
SC: Vigorously shake or roll the vial to mix medication immediately prior to administration (solution should be uniformly cloudy).
Divide doses > 4 ml into two syringes and inject into two separate sites. Invert syringe 23
times and roll vigorously between palms prior
to administration. To minimize skin irritation,
ensure that the needle is empty of drug, and do
not expel air in needle before giving the
injection. Do not use ice on injection site, as it
may decrease drug absorption. Rotate sites for
administration among thigh, abdomen, and
upper arm. Administer new injections at least
one inch from old site. Avoid sites that are
tender, bruised, red, or hard.
Monitor CBC and liver and renal function during
therapy.
Drug is contraindicated in patients with hypersensitivity to azacitidine or mannitol and those
with advanced malignant hepatic tumors.
(Celgene Corp., 2012b)

Act in S phase;
inhibit enzyme
production for
DNA synthesis,
leading to strand
breaks or premature chain termination

Capecitabine
(Xeloda)

PO

Breast and metastatic colon cancers

Dose-limiting toxicities: Diarrhea,


palmar-plantar erythrodysesthesia
(hand-foot syndrome)
Mucositis, nausea, vomiting, anemia,
increased bilirubin, fatigue

Patient education regarding importance of reporting toxicity and dose reduction is critical.
Drug is contraindicated in patients with known
hypersensitivity to 5-FU.
Monitor PT and INR closely, as capecitabine increases effect of warfarin.
Administer with food and water.
(Genentech, Inc., 2010)

Cladribine
(Leustatin)

IV

Hairy cell leukemia

Dose-limiting toxicities: Myelosuppression, neurotoxicity


Fever, nausea, vomiting, hypersensitiv
ity reaction, TLS, nephrotoxicity (highdose therapy)

Allopurinol and IV hydration are recommended for patients with high tumor burden to prevent TLS.
Use with caution in patients with liver and renal
dysfunction.
(Centocor Ortho Biotech Products, L.P., 2012)

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 7. Characteristics of Chemotherapeutic Agents (Continued)


Classification
Antimetabolites (cont.)

Mechanism
of Action
A purine nucleoside antimetabolite that incorporates into the
DNA chain inhibiting DNA repair

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

IV

Patients ages
121 with relapsed or refractory ALL

Dose-limiting toxicities: Bone marrow


suppression (including anemia, leukopenia, thrombocytopenia, neutropenia, and febrile neutropenia), infection, hepatobiliary toxicity, renal toxicity
Nausea, vomiting, diarrhea, rare cases
of systemic inflammatory response
syndrome/capillary leak syndrome
and cardiac toxicity including tachycardia, pericardial effusion, and left
ventricular systolic dysfunction; TLS,
headache, pruritus, rash

Continuous IV fluid administration during the 5


days of chemotherapy administration is encouraged to reduce risk of TLS and other adverse
effects.
Use prophylactic steroids to help prevent systemic inflammatory response syndrome and capillary leak syndrome.
Give allopurinol if hyperuricemia is expected.
Monitor respiratory status and blood pressure
during infusion.
Monitor renal and hepatic function during the
days of administration.
Monitor hematologic status closely following
treatment.
(Genzyme Corp., 2013)

Cytarabine
(cytosine arabinoside,
ARA-C,
Cytosar-U)

IV, SC, IT

ALL, AML, CML,


CNS leukemia

Dose-limiting toxicity: Myelosuppression


Nausea, vomiting, anorexia, fever, mucositis, diarrhea, hepatic dysfunction,
rash, pruritus, localized pain and/or
thrombophlebitis at IV site, photophobia
High-dose (13 g/m2): cerebellar toxicity, keratitis (treat with dexamethasone ophthalmic drops), dermatologic toxicities

Determine if ordered dose is standard dose or


high dose; administer according to institutional guidelines.
Note: Toxicities vary depending upon rate of
high-dose cytarabine administration. Continuous-infusion cytarabine is associated with pulmonary toxicity (fluid overload), and bolus administration is associated with cerebellar toxicities. Specific nursing interventions are warranted for each.
For IT administration: Use preservative-free saline.
Allopurinol and IV hydration are recommended
for newly diagnosed patients with AML or patients with high tumor burden to prevent TLS.
(APP Pharmaceuticals, LLC, 2008a)

Cytarabine
liposomal
(DepoCyt)

IT only

Lymphomatous
meningitis

High-dose: mucositis, diarrhea, chemical arachnoiditis (nausea, vomiting,


headache, fever), neurotoxicity, seizure, nausea, vomiting, constipation,
weakness

Do not use in pediatric patients.


Administer IT only.
Patients should lie flat for 1 hour after lumbar
puncture.
Monitor closely for immediate toxic reactions.
Administer dexamethasone 4 mg BID (PO or IV)
for 5 days (start day of cytarabine administration) to decrease symptoms of chemical arachnoiditis.
(Sigma-Tau Pharmaceuticals, Inc., 2011a)

33

(Continued on next page)

Chapter 3. Principles of Antineoplastic Therapy

Clofarabine
(Clolar)

34

Table 7. Characteristics of Chemotherapeutic Agents (Continued)

Antimetabolites (cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Decitabine
(Dacogen)

IV

MDS

Myelosuppression, fever, fatigue, nausea, cough, constipation, diarrhea,


hyperglycemia, petechiae, peripheral edema

Delay treatment if SCr 2 mg/dl or total bilirubin


2 ULN until resolved.
Use within 15 min of reconstitution. If this is not
possible, return to pharmacy so solution can be
prepared in cold infusion fluid.
(Eisai Inc., 2010a)

Floxuridine
(FUDR)

Intra-arterial, IV

Adenocarcinoma
of GI tract with
metastasis to liver, gallbladder, or
bile duct

Myelosuppression, nausea, vomiting,


diarrhea, mucositis, alopecia, photosensitivity, darkening of the veins, abdominal pain, gastritis, enteritis, hepatotoxicity, palmar-plantar erythrodysesthesia

Do not use in pediatric patients.


Recommendations about dose reduction apply to
patients with compromised liver function. Adjust
dose per institutional protocol and monitor hepatic function carefully.
(APP Pharmaceuticals, LLC, 2008b)

Fludarabine
(Fludara)

IV, PO

CLL

Dose-limiting toxicity: Myelosuppression


Nausea, vomiting, diarrhea, rash, neurotoxicity, interstitial pneumonitis,
weakness, hemolytic anemia, cough,
infection

Administer as a 30-min infusion.


Monitor PFTs.
Allopurinol and IV hydration are recommended
for newly diagnosed patients with CLL or patients with high tumor burden to prevent TLS.
Do not use in combination with pentostatinmay
cause severe pulmonary toxicity.
Use with caution in patients with renal impairment.
Tablets may be taken with or without food.
Do not chew, break, or crush tablets.
(Teva Parenteral Medicines, Inc., 2011)

Fluorouracil
(5-FU, Adrucil)

IV, topical

Colorectal,
breast, pancreatic, and stomach
cancers

Dose-limiting toxicities: Mucositis,


myelosuppression
Nausea, anorexia, vomiting, diarrhea,
alopecia, ocular toxicities (e.g., increased lacrimation, photosensitivity),
darkening of the veins, dry skin, cardiac toxicity (rare), neurotoxicity

Ensure that patients take year-round photosensitivity precautions; encourage sunscreen use if
patients must be exposed.
Leucovorin often is given concurrently to enhance 5-FU activity.
Apply ice chips to the oral cavity 1015 min
pre- and post-IV bolus dose of 5-FU to reduce
oral mucositis in patients with GI malignancies. Not recommended in patients receiving
capecitabine or oxaliplatin because of potential
discomfort with exposure to coldness.
(Teva Parenteral Medicines, Inc., 2012)

Gemcitabine
(Gemzar)

IV

Pancreatic,
breast, and ovarian cancers,
NSCLC

Dose-limiting toxicity: Myelosuppression (especially thrombocytopenia)


Nausea, vomiting, fever, flu-like symptoms, rash, peripheral edema, pulmonary toxicity with increased infusion time

Do not use in pediatric patients.


Infuse over 30 min; infusion longer than 60 min or
more than weekly can increase pulmonary toxicity.
Use with caution in patients with renal impairment.
(Eli Lilly and Co., 2011)
(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 7. Characteristics of Chemotherapeutic Agents (Continued)


Classification
Antimetabolites (cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

PO

ALL

Dose-limiting toxicity: Myelosuppression


Mucositis, nausea, hyperuricemia, alopecia, hyperpigmentation

Reduce oral dose by 75% when used concurrently with allopurinol.


Patients should take drug on an empty stomach,
1 hour before or 2 hours after meals.
(Gate Pharmaceuticals, 2011)

Methotrexate

IM, IV, IT, PO,


SC

HD, NHL, leukemia; CNS metastasis; lung, breast,


and head and neck
cancers; gestational trophoblastic tumor; osteogenic
sarcoma; rheumatoid arthritis; psoriasis; gestational
choriocarcinoma,
chorioadenoma
destruens, and hydatidiform mole

Dose-limiting toxicities: Hepatotoxicity, renal toxicity


Mucositis, nausea, myelosuppression,
oral or GI ulceration, pneumonitis,
photosensitivity, neurotoxicity associated with high-dose therapy

Drug is yellow in color.


High doses must be followed by timely administration of leucovorin and vigorous hydration.
Follow dosing schedule carefully.
Monitor serum methotrexate levels until 0.1
mmol. Monitor urine pH and maintain at 7 before treatment and until methotrexate levels are
0.1 mmol.
Instruct patients on strict mouth care.
Patients must take photosensitivity precautions.
Ensure that patients avoid taking multivitamins
with folic acid.
Multiple drug interactions (e.g., NSAIDs, alcohol,
aspirin, warfarin, aminoglycosides) are possible.
Methotrexate is contraindicated in patients with
pleural or pericardial effusions and ascites because of severe toxicity from methotrexate accumulation.
Glucarpidase (Voraxaze) is FDA approved for
patients with delayed methotrexate clearance
due to renal impairment. This drug reduces
systemic methotrexate levels by rapidly converting methotrexate to glutamate and 4-deoxy4-amino-N10-methylpteroic acid (DAMPA).
(BTG International Inc., 2013; Hospira, Inc., 2011b)

Nelarabine
(Arranon)

IV

T-cell acute lymphoblastic leukemia and T-cell


lymphoblastic lymphoma

Dose-limiting toxicity: Neurotoxicity


Myelosuppression, headache, nausea, vomiting, diarrhea, constipation,
cough, peripheral edema, fatigue, peripheral neuropathy, dyspnea, neurologic toxicities (somnolence, seizures,
ataxia)

Given as undiluted IV infusion over 2 hours for


adults and 1 hour for pediatrics.
Administer with appropriate supportive care
medications to prevent hyperuricemia and TLS.
Discontinue for grade 2 neurologic events
(severe somnolence, seizure, and peripheral
neuropathy).
Use caution in patients with renal or hepatic dysfunction.
(GlaxoSmithKline, 2011b)

35

(Continued on next page)

Chapter 3. Principles of Antineoplastic Therapy

Mercaptopurine (6-MP,
Purinethol)

36

Table 7. Characteristics of Chemotherapeutic Agents (Continued)

Antimetabolites (cont.)

Mechanism
of Action
Disrupts folatedependent metabolic processes
essential for cell
replication

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Pemetrexed
(Alimta)

IV

Given in combination with cis


platin for the
treatment of malignant pleural mesothelioma; nonsquamous NSCLC initial treatment in
combination with
cisplatin or as a
single-agent after prior chemotherapy

Dose-limiting toxicity: Myelosuppression


Side effects with pemetrexed plus cisplatin regimen include myelosuppression, fatigue, nausea, vomiting, chest
pain, and dyspnea. Side effects are
reduced with vitamin supplementation.
Renal and liver toxicity

Infuse over 10 minutes.


To reduce treatment-related hematologic and GI
toxicity, administer folic acid 3501,000 mcg
PO daily starting 1 week prior to the first cycle
and daily for three weeks after final cycle. Give
vitamin B12 injection 1,000 mcg IM 1 week before first cycle and repeat every 9 weeks until
treatment is completed.
Dexamethasone 4 mg BID for 3 days starting the
day before treatment decreases incidence of
skin rash.
Monitor CBC on days 8 and 15. Hold treatment
if absolute neutrophil count < 1,500 cells/mm3,
platelet count < 100,000 cells/mm3, or creatinine clearance < 45 ml/min.
Monitor renal and hepatic function.
The concurrent use of NSAIDs may increase the
risk of renal damage.
(Eli Lilly and Co., 2013)

Pentostatin
(Nipent)

IV

Hairy cell leukemia

Dose-limiting toxicity: Myelosuppression


Fever, chills, nausea, vomiting, rash,
renal failure, confusion, hepatic enzyme elevation, lymphocytopenia,
heightened infection risk, cough

Administer with 5001,000 ml 5% dextrose in


NS solution prior to the infusion and an additional 500 ml after infusion.
Do not administer with fludarabine, carmustine, etoposide, or high-dose cyclophosphamide.
(Bedford Laboratories, 2010c)

Pralatrexate
(Folotyn)

IV

Peripheral T-cell
lymphoma

Dose-limiting toxicity: Myelosuppression


Mucositis, dermatologic reactions, TLS,
edema, fatigue, nausea

Must give prophylactic folic acid and vitamin B12


supplements. Supplement patients with vitamin
B12 1 mg IM every 810 weeks and folic acid
11.25 mg PO daily.
Monitor liver and renal function.
Concurrent use with drugs with extensive renal clearance may delay pralatrexate clearance.
(Allos Therapeutics, 2011)

Thioguanine
(Tabloid,
6-TG)

PO

AML

Dose-limiting toxicity: Myelosuppression


Hyperuricemia, nausea, hepatotoxicity, diarrhea

Monitor hepatic function.


(GlaxoSmithKline, 2008)

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 7. Characteristics of Chemotherapeutic Agents (Continued)


Classification
Antitumor
antibiotics

Mechanism
of Action
Bind with DNA,
thereby inhibiting
DNA and RNA
synthesis

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

IV, SC, IM, intrapleural

Malignant pleural effusion; squamous cell cancer


of head and neck;
cervical, vulvar,
penile, and testicular cancers; HL;
NHL

Dose-limiting toxicities: Hypersensitivity or anaphylactic reaction (rare),


pulmonary toxicity
Hyperpigmentation, alopecia, photosensitivity, renal toxicity, hepatotoxicity, fever, chills, erythema, rash, mucositis

Patients with lymphoma have a higher incidence


of anaphylaxis after receiving bleomycin than
do other patients who receive the drug. Therefore (per institutional protocol), a test dose of
12 units IV, IM, or SC may be administered
before the first dose of bleomycin in patients
with lymphoma.
Patients who have received prior bleomycin are
at risk for pulmonary toxicity when exposed to
oxygen during surgery. Ensure that patients
and family members understand the lifelong
necessity of disclosing previous use of bleomycin when future needs for anesthesia occur to prevent a fatal episode of pulmonary
failure.
Because of the dose-related incidence of pulmonary fibrosis, the cumulative lifetime dose
should not exceed 400 units.
PFTs are recommended at initiation of bleomycin and every 12 months thereafter. Consider stopping drug if a 30%35% decrease from
pretreatment values occurs. Acetaminophen
and an antihistamine may decrease fever and
chills in first 24 hours after administration.
(Bedford Laboratories, 2009)

Dactinomycin
(actinomycin D,
Cosmegen)

IV

Ewing sarcoma,
Wilms tumor, testicular cancer,
gestational trophoblastic disease, rhabdomyosarcoma

Dose-limiting toxicity: Myelosuppression


Nausea, vomiting, alopecia, mucositis,
diarrhea, ovarian or sperm suppression, radiation recall (hyperpigmentation of previously irradiated areas), sinusoidal obstruction syndrome, hepatic and renal toxicity

Dactinomycin is a vesicant.
This drug may be ordered in micrograms, so
check the dose carefully.
Contraindicated in patients with concurrent or recent chickenpox or herpes zoster.
Avoid within 2 months of radiation therapy for
right-sided Wilms tumor.
(Ovation Pharmaceuticals, 2008)

Mitomycin
(Mutamycin)

IV
Intravesicular

Pancreatic, stomach, and bladder


cancers

Dose-limiting toxicities: Myelosuppression, CHF (doses > 30 mg/m2)


Nausea, vomiting, anorexia, alopecia,
mucositis, renal toxicity, pulmonary
toxicity, fatigue

Drug is purple/blue in color.


Mitomycin is a vesicant.
Nadir occurs 46 weeks after treatment begins.
Acute shortness of breath and bronchospasm
can occur very suddenly when this drug is given with a vinca alkaloid.

37

(Continued on next page)

Chapter 3. Principles of Antineoplastic Therapy

Bleomycin
(Blenoxane)

38

Table 7. Characteristics of Chemotherapeutic Agents (Continued)


Mechanism
of Action

Antitumor
antibiotics
(cont.)

Antitumor
antibiotics
(anthracyclines)

Drug

Route of
Administration

Indications

Side Effects

Mitomycin
(Mutamycin)
(cont.)

Bind with DNA,


thereby inhibiting
DNA and RNA
synthesis

Nursing Considerations
Contraindicated in patients with coagulation disorders.
Hemolytic-uremic syndrome has been seen with
single dose 60 mg or cumulative doses 50
mg/m2.
(Bristol-Myers Squibb Co., 2006c)

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Mitoxantrone
(Novantrone)

IV

Breast and prostate cancers,


AML, multiple
sclerosis

Dose-limiting toxicities: Myelosuppression, cardiotoxicity


Arrhythmia (if patient was treated with
doxorubicin), nausea, vomiting, mucositis, alopecia, edema, fever, weakness, cardiotoxicity; drug may turn
the urine blue-green and can cause
sclera to turn bluish.

Fatal if given intrathecally.


Mitoxantrone is an irritant with vesicant potential.
Drug is blue in color.
Risk of cardiotoxicity with mitoxantrone is less
than that with doxorubicin, but prior anthracycline use, chest irradiation, or cardiac disease
increases risk.
Prior to beginning therapy, evaluate patients for
cardiac signs/symptoms including obtaining
MUGA scan and baseline LVEF.
(EMD Serono, Inc., 2010)

Daunorubicin (Cerubidine, Daunomycin)

IV

ALL in children,
AML

Dose-limiting toxicities: Myelosuppression, cardiotoxicity


Nausea, vomiting, alopecia, hyperuricemia, radiation recall, ovarian or
sperm suppression; drug may turn
the urine red.

Daunorubicin is a vesicant.
Drug is red in color.
Test patients cardiac ejection fraction scan before starting therapy.
Use in caution in patients with renal or hepatic
dysfunction.
Total lifetime dose in adults is 550 mg/m2 without
cardiovascular risk factors and 400 mg/m2 in
adults receiving chest irradiation.
(Bedford Laboratories, 2010a)

Daunorubicin
citrate liposomal (DaunoXome)

IV

AIDS-related Kaposi sarcoma

Dose-limiting toxicities: Myelosuppression, cardiotoxicity


Nausea, vomiting, alopecia, fatigue, fever, diarrhea, hyperuricemia, radiation recall, ovarian or sperm suppression; drug may turn the urine red.

Drug is red in color.


Daunorubicin citrate liposomal is not a vesicant
but should be considered an irritant; take caution to avoid extravasation.
Consider dose reduction in patients with renal or
hepatic dysfunction.
Test patients cardiac ejection fraction before
starting daunorubicin liposomal therapy.
This drug must be mixed in D5W only. Do not use
in-line filters.
(Gilead Sciences, 2011)

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 7. Characteristics of Chemotherapeutic Agents (Continued)


Classification
Antitumor
antibiotics
(anthracyclines) (cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

IV

Breast, prostate,
ovarian, stomach, bladder, thyroid, and small
cell lung cancers;
MM, HL, NHL,
ALL, AML; Wilms
tumor, lymphoma,
sarcoma, neuroblastoma

Dose-limiting toxicities: Myelosuppression, cardiotoxicity, hepatotoxicity


Nausea, vomiting, alopecia, mucositis, radiation recall, arrhythmia, hyperuricemia, photosensitivity; drug may
turn the urine red.

Doxorubicin is a vesicant.
Drug is red in color.
Doxorubicin may cause a flare reaction.
Test patients cardiac ejection fraction before
starting therapy.
Do not exceed a lifetime cumulative dose of 550
mg/m2 (450 mg/m2 if the patient has had prior
chest irradiation or concomitant cyclophosphamide treatment).
Consider initiating dexrazoxane (Zinecard) for
patients who have received a cumulative dose
of 300 mg/m2 and are continuing doxorubicin
treatment. In pediatrics, dexrazoxane may be
used concurrently.
(Pfizer Inc., 2010)

Doxorubicin liposomal
(Doxil)

IV

AIDS-related Kaposi sarcoma,


ovarian cancer,
MM

Dose-limiting toxicities: Myelosuppression, cardiotoxicity


Nausea, vomiting, alopecia, mucositis,
arrhythmia, hyperuricemia, radiation
recall, palmar-plantar erythrodysesthesia, photosensitivity, hypersensitivity reaction, electrolyte imbalance;
drug may turn the urine red.

Drug is red in color.


Doxorubicin liposomal is not a vesicant but
should be considered an irritant; take caution to
avoid extravasation.
The same warnings as with conventional doxorubicin apply regarding cardiovascular complications.
Use only with D5W.
Do not substitute for Adriamycin.
Start infusion at 1 mg/min over at least 30 min to
minimize infusion-related reactions. Do not use
in-line filter.
(Janssen Products, LP, 2013)

Epirubicin
(Ellence)

IV

Breast cancer

Dose-limiting toxicities: Myelosuppression, cardiotoxicity


Nausea, vomiting, mucositis, diarrhea,
alopecia, amenorrhea, infection, radiation recall; drug may turn the urine
red.

Epirubicin is a vesicant.
Drug is red in color.
Consider dose reduction in patients with liver
dysfunction.
Not recommended in patients with severe hepatic dysfunction.
Reduce dose in patients with SCr > 5 mg/dl.
Cumulative dosing should not exceed 900 mg/
m2.
Test patients cardiac ejection fraction before
starting epirubicin therapy.
(Pfizer Inc., 2011)

39

(Continued on next page)

Chapter 3. Principles of Antineoplastic Therapy

Doxorubicin
(Adriamycin)

40

Table 7. Characteristics of Chemotherapeutic Agents (Continued)


Mechanism
of Action

Route of
Administration

Indications

Side Effects

Nursing Considerations

Idarubicin
(Idamycin)

IV

ANLL

Dose-limiting toxicities: Myelosuppression, cardiomyopathy


Nausea, vomiting, alopecia, vein itching, radiation recall, rash, mucositis,
diarrhea, GI hemorrhage; drug may
turn the urine red or darker yellow.

Idarubicin is a vesicant. Infuse slowly over 1015


min into free-flowing side-arm infusion.
Drug is red-orange in color.
Cardiotoxicity of idarubicin is less than that of
daunorubicin.
Cumulative doses > 150 mg/m2 idarubicin are associated with decreased ejection fraction.
Local reactions (hives at injection site) may occur.
Consider dose reduction in patients with renal or
hepatic impairment.
Do not administer to patients with bilirubin > 5
mg/dl.
(Teva Parenteral Medicines, Inc., 2009a)

Valrubicin
(Valstar)

Intravesical

Intravesical therapy of BCG-refractory in situ bladder cancer

Dysuria, bladder spasm and irritation,


urinary incontinence, leukopenia, hyperglycemia; drug may turn the urine
red.

Do not use in pediatric patients.


Valrubicin is administered as an intravesicular
bladder lavage.
Administer through non-PVC tubing.
(Endo Pharmaceuticals Solutions Inc., 2012)

Degrades the
chimeric PML/
RAR-alpha protein; degrades
the NB4 human
promyelocytic
leukemia cells
to cause partial
maturation and
trigger apoptosis;
causes the release of toxic free
radicals inside
the cell that triggers apoptosis of
the APL cell

Arsenic
trioxide
(Trisenox)

IV

APL

Fatigue, prolonged QT interval, APL


differentiation syndrome, leukocytosis, headache, nausea, vomiting, diarrhea, musculoskeletal pain, peripheral neuropathy, tachycardia, edema,
fever, insomnia, dermatitis, cough,
dyspnea

Use with caution with other agents that prolong


QT/QTc interval. Obtain baseline ECG prior to
therapy. Ensure QTc interval < 500 msec prior to infusion. Periodic QTc intervals should be
measured during therapy (e.g., weekly) per institutional guidelines.
Use with caution in patients with renal impairment. Monitor electrolytes during therapy. Maintain serum potassium > 4 mEq/L and magnesium > 1.8 mg/dl.
(Cephalon, Inc., 2010)

Inhibits protein
synthesis

Asparaginase
(Elspar)

IV, SC, IM

ALL

Dose-limiting toxicity: Pancreatitis


Nausea, vomiting, hepatotoxicity, fever,
hyperglycemia, anaphylaxis, coagulopathy, hypoalbuminemia, hypersensitivity reaction, renal toxicity, thrombus

Giving the drug IM greatly reduces the incidence


of anaphylaxis.
Keep medications to treat anaphylaxis at bedside.
(Lundbeck, 2013)

Antitumor
antibiotics
(anthracyclines) (cont.)

Miscellaneous

Drug

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 7. Characteristics of Chemotherapeutic Agents (Continued)


Classification

Mechanism
of Action

Miscellaneous
(cont.)

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

IM

ALL, for patients


who have developed sensitivity to
E. coli-derived asparaginase

Nausea, vomiting, hepatotoxicity, fever,


hyperglycemia, anaphylaxis, pancreatitis, coagulopathy, hypersensitivity
reaction, renal toxicity, thrombus

Keep medications to treat anaphylaxis at bedside.


Limit the volume of reconstituted Erwinaze at
a single injection site to 2 ml; if reconstituted
dose to be administered is > 2 ml, use multiple
injection sites.
(EUSA Pharma [USA], Inc., 2011)

Pegaspargase
(Oncaspar)

IM, IV

ALL (may be
used upfront or
for those who
have developed
hypersensitivity to
asparaginase)

Hepatotoxicity, coagulopathy, anaphylaxis, hyperglycemia

Longer half-life (56 days) than asparaginase (12


days); therefore, is dosed every 14 days versus
daily or every 3 days. Check dosing carefully.
Risk of anaphylaxis is less than that of asparaginase.
(Sigma-Tau Pharmaceuticals, Inc., 2011b)

Acts in S phase
as antimetabolite

Hydroxyurea
(Hydrea,
Mylocel)

PO

CML, malignant
melanoma, squamous cell cancer
of the head and
neck, metastatic ovarian cancer,
sickle-cell anemia

Dose-limiting toxicities: Myelosuppression, nausea, vomiting, diarrhea,


renal failure, mucositis, fever, hyperuricemia, rash, hepatotoxicity, second
malignancies

Do not open capsules.


Adjust the dose according to WBC counts; monitor WBCs at least every 2 weeks, and stop
treatment until counts recover. Do not change
the dose frequently in older patients because
they may be more sensitive to the medication.
Instruct patients on strict mouth care.
Doses may be divided within the 24-hour period
to decrease nausea and vomiting.
(Bristol-Myers Squibb Co., 2011b)

Inhibits adrenal steroid production

Mitotane
(Lysodren)

PO

Adrenocortical
cancer

Nausea, vomiting, mucositis, adrenal


insufficiency, lethargy, rash

Monitor patients on warfarin therapy closely with


PT/INR.
Adrenal steroid replacement is indicated.
Consider dose reduction in patients with renal or
hepatic impairment.
(Bristol-Myers Squibb Co., 2006b)

May inhibit protein, RNA, and


DNA synthesis

Procarbazine
(Matulane)

PO

HL

Dose-limiting toxicity: Myelosuppression


Nausea, vomiting, hepatic dysfunction

Patients should avoid foods high in tyramine,


such as aged cheeses, air-dried or cured
meats, fava or broad bean pods, tap/draft beer,
wine (> 120 ml), vermouth, marmite concentrate, sauerkraut, and soy sauce and other soybean condiments because procarbazine inhibits monoamine oxidase.
Patients should avoid alcohol for possible
Antabuse-like reaction.
(Sigma-Tau Pharmaceuticals, Inc., 2012)

41

(Continued on next page)

Chapter 3. Principles of Antineoplastic Therapy

Asparaginase
Erwinia chrysanthemi (Erwinaze)

42

Table 7. Characteristics of Chemotherapeutic Agents (Continued)

Miscellaneous
(cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Inhibits growth
phase of microtubules, arresting
cell cycle at G2/M
phase

Eribulin
(Halaven)

IV

Breast cancer

Dose-limiting toxicities: Neutropenia,


neurotoxicity
Peripheral neuropathy, fatigue, alopecia, nausea, constipation, anemia,
QTc prolongation

Monitor electrolytes, ECG, and renal and liver


function tests.
Not compatible with D5W.
(Eisai Inc., 2010b)

Inhibits the enzymatic activity


of HDAC, which
allows for the
accumulation of
acetyl groups on
histone lysine
residue, which
results in cell cycle arrest and/
or apoptosis
of some transformed cells

Romidepsin
(Istodax)

IV

Cutaneous and
peripheral T-cell
lymphoma

Dose-limiting toxicities: Myelosuppression, life-threatening infections


QTc prolongation, fatigue, fever, pruritus, nausea, vomiting, anorexia, constipation, diarrhea, TLS

Obtain baseline and periodic ECG.


Monitor and correct electrolytes.
(Celgene Corp., 2013)

Inhibits the enzymatic activity of


HDAC, which allows for the accumulation of
acetyl groups on
the histone lysine residue,
which results in
cell cycle arrest
and/or apoptosis
of some transformed cells

Vorinostat
(Zolinza)

PO

Cutaneous T-cell
lymphoma

Dose-limiting toxicities: Thrombocytopenia, diarrhea


Anemia, fatigue, nausea, thromboembolism, anorexia, dysgeusia, proteinuria, QTc prolongation

Instruct patients to take once daily with food.


Monitor CBC, electrolytes, glucose, and SCr every 2 weeks during first 2 months and monthly
thereafter because of possible hyperglycemia
and QT prolongation.
Capsules should not be opened or crushed.
Drug may interact with warfarin (Coumadin) (increasing PT/INR) and other HDAC inhibitors
(valproic acid) (severe thrombocytopenia and
GI bleeding).
(Merck & Co., Inc., 2009)

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 7. Characteristics of Chemotherapeutic Agents (Continued)


Classification
Miscellaneous
(cont.)

Nitrosoureas

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Ixabepilone
(Ixempra)

IV

Metastatic or locally advanced


breast cancer

Dose-limiting toxicities: Peripheral sensory neuropathy, myelosuppression


Fatigue, myalgia, alopecia, nausea,
vomiting, mucositis, diarrhea, musculoskeletal pain

CYP3A4 inhibitors may increase ixabepilone


concentration, and CYP3A4 inducers may decrease ixabepilone concentration. Avoid St.
Johns wort.
Premedicate with diphenhydramine and famotidine or ranitidine 1 hour prior to dose to decrease risk of hypersensitivity reaction.
Mix only in LR in non-PVC bag. Administer
through 0.21.2 micron in-line filter.
(Bristol-Myers Squibb Co., 2011c)

Inhibits protein
synthesis and
is independent
of direct Bcr-Abl
binding

Omacetaxine
(Synribo)

SC

CML in chronic or accelerated


phase with resistance and/or intolerance to 2 or
more TKIs

Dose-limiting toxicity: Myelosuppression


Thrombocytopenia with bleeding risk,
hyperglycemia, nausea, vomiting, diarrhea, alopecia, skin rash, injectionsite reactions

Monitor patient for bleeding.


Rotate injection sites.
(Teva Pharmaceuticals USA, Inc., 2012)

Break DNA helix,


interfering with
DNA replication;
cross the bloodbrain barrier

Carmustine
(BiCNU)

IV, implantation
(Gliadel wafer)

HL, NHL, CNS tumors, MM

Dose-limiting toxicity: Myelosuppression


Nausea, vomiting, renal toxicity, hepatotoxicity, pulmonary fibrosis, ovarian
or sperm suppression

Nadir occurs 46 weeks after therapy starts.


Because of delayed toxicity, successive treatments usually are given no more frequently
than once every 68 weeks.
Rapid infusion may cause burning along the vein
and flushing of the skin (infuse over at least 2
hours).
Mix in D5W non-PVC bag.
Long-term therapy can result in irreversible pulmonary fibrosis, which may present as an insidious
cough and dyspnea or sudden respiratory failure.
(Bristol-Myers Squibb Co., 2007)

Lomustine
(CeeNU)

PO

CNS and brain


tumors; HL

Dose-limiting toxicity: Myelosuppression


Nausea, vomiting, alopecia, renal toxicity, hepatic toxicity, mucositis, anorexia, pulmonary fibrosis

Because of delayed myelosuppression, do not


repeat the dose more than once every 6 weeks.
Administer on an empty stomach.
Monitor PFTs, LFTs, and renal function.
(Bristol-Myers Squibb Co., 2006a)

43

(Continued on next page)

Chapter 3. Principles of Antineoplastic Therapy

Semisynthetic analog of epothilone B; binds


to beta-tubulin
on microtubules,
leading to cell
death by blocking cells in mitotic phase of cell
division cycle

44

Table 7. Characteristics of Chemotherapeutic Agents (Continued)


Mechanism
of Action

Nitrosoureas
(cont.)

Camptothecins

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Plant
alkaloids
(epipodophyllotoxins)

Act in S phase;
inhibit topoisomerase I; cause
double-strand
DNA changes

Induce irreversible blockade of


cells in premitotic phases of
cell cycle (late
G2 and S phases); interfere with
topoisomerase II
enzyme reaction

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Streptozocin
(Zanosar)

IV

Metastatic isletcell pancreatic


carcinoma

Dose-limiting toxicity: Renal toxicity


Myelosuppression, nausea, vomiting,
hypoglycemia, proteinuria, hepatotoxicity

Streptozocin is an irritant.
Nephrotoxicity may be dose limiting.
This drug may alter glucose metabolism in some
patients.
Rapid infusion may cause burning along the vein.
(Sicor Pharmaceuticals, 2006)

Irinotecan
(Camptosar)

IV

Metastatic
colorectal cancer

Dose-limiting toxicity: Diarrhea


Myelosuppression, alopecia, fever,
nausea, vomiting, mucositis, increased bilirubin, weakness

Do not use in pediatric patients.


This drug can cause early and late diarrhea,
which can be dose limiting. Early diarrhea can
occur within 24 hours of administration and
generally is cholinergic. Many institutions use
atropine to treat early diarrhea. Refer to institutional protocol regarding dosing and administration of atropine and other antidiarrheals.
(Hospira, Inc., 2011a)

Topotecan
(Hycamtin)

IV, PO

Metastatic ovarian cancer, cervical cancer, SCLC

Dose-limiting toxicity: Diarrhea


Myelosuppression, alopecia, nausea,
vomiting, headache, fatigue, fever, interstitial lung disease

Consider dose reduction in patients with renal


impairment.
Do not crush, chew, or break capsules.
(GlaxoSmithKline, 2009)

Etoposide
(VP-16,
Toposar,
VePesid)
Etoposide
phosphate
(Etopophos)

IV, PO

Testicular cancer,
SCLC

Dose-limiting toxicity: Myelosuppression


Nausea, vomiting, alopecia, anorexia, hypotension, hypersensitivity reaction, anaphylaxis
High-dose: Mucositis, diarrhea, myocardial infarction, angina

Do not administer this drug by means of rapid


IV infusion or IV push. Infuse over 3060 min
to avoid hypotension.
Monitor patients blood pressure during infusion.
Prior to use, dilute the drug to a final concentration of 0.20.4 mg/ml to prevent precipitation.
Monitor for crystallization during infusion.
If a patient has an allergic reaction to etoposide, premedicate with diphenhydramine.
Do not administer to patients with bilirubin > 5
mg/dl.
Consider dose reduction in patients with renal
or hepatic impairment.
(Bedford Laboratories, 2010b; Bristol-Myers
Squibb Co., 2011a)

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 7. Characteristics of Chemotherapeutic Agents (Continued)


Classification

Mechanism
of Action

Plant
alkaloids
(epipodophyllotoxins)
(cont.)

Plant
alkaloids
(taxanes)

Stabilize microtubules, inhibiting


cell division; effective in G2 and
M phases

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

IV

Childhood ALL

Dose-limiting toxicity: Myelosuppression


Hypotension, anaphylaxis, nausea,
vomiting, mucositis, alopecia

Drug may cause an allergic reaction.


Do not administer via rapid infusion; infuse over
3060 min; monitor patients blood pressure
during the infusion.
Administer through non-PVC tubing.
Consider dose reduction in patients with renal or
hepatic impairment.
(Bristol-Myers Squibb Co., 2011e)

Cabazitaxel
(Jevtana)

IV

Prostate cancer

Hypersensitivity reaction, fatigue, diarrhea, nausea, vomiting, myelosuppression, peripheral neuropathy, abdominal pain, back pain, arthralgia,
asthenia

Premedicate as follows to prevent hypersensitivity reaction, including anaphylaxis, at least 30


min before treatment: IV antihistamine, corticosteroid, and an H2 antagonist.
Administer over 1-hour infusion.
Use with caution in patients with renal impairment.
Not recommended in patients with severe hepatic impairment.
(sanofi-aventis U.S. LLC, 2012)

Docetaxel
(Taxotere)

IV

NSCLC; breast,
head and neck,
prostate, and
gastric cancers

Myelosuppression, hypersensitivity reaction, fluid retention, alopecia, skin


and nail changes, mucositis, nausea,
vomiting, paresthesia, neurotoxicity

Do not use in pediatric patients.


Docetaxel is an irritant. Extravasation may lead
to edema, erythema, and occasional pain
and blister formation.
Premedicate as follows to reduce the severity of hypersensitivity reaction and fluid retention: dexamethasone 8 mg PO BID, beginning
1 day prior to docetaxel treatment and continuing for the day of treatment and 1 day after.
Do not use PVC tubing or bags to administer
docetaxel.
Consider dose reduction in patients with hepatic impairment.
(sanofi-aventis U.S. LLC, 2010)

45

(Continued on next page)

Chapter 3. Principles of Antineoplastic Therapy

Teniposide
(VM-26,
Vumon)

46

Table 7. Characteristics of Chemotherapeutic Agents (Continued)

Plant
alkaloids
(taxanes)
(cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Paclitaxel
(Taxol)

IV

Metastatic breast,
and ovarian, cancers, NSCLC,
AIDS-related Kaposi sarcoma

Dose-limiting toxicities: Peripheral


neuropathy, hypersensitivity reaction
Myelosuppression, alopecia, facial
flushing, myalgia, fatigue, cardiac arrhythmias, mucositis, diarrhea, nausea, vomiting

Do not use in pediatric patients.


Paclitaxel is an irritant and potential vesicant. Extravasation may lead to local pain, edema, and
erythema at the infusion site. There are reports
of necrosis.
Drug is mixed in a mineral oillike solvent that
can cause infusion-related hypersensitivity reactions.
Premedicate as follows to help to prevent hypersensitivity reaction, including anaphylaxis, 30
60 min before treatment: cimetidine 300 mg or
famotidine 20 mg IV, diphenhydramine 50 mg
IV, and (unless contraindicated) dexamethasone 20 mg IV (Solimando, 2008).
Filter paclitaxel with a 0.2 micron in-line filter.
Use glass bottles or non-PVC (polyolefin or polypropylene) bags to administer paclitaxel; do not
use PVC tubing or bags.
Consider dose reduction in patients with renal or
hepatic impairment.
To prevent severe myelosuppression, give paclitaxel before platinum-containing drugs.
(Bristol-Myers Squibb Co., 2011d)

Paclitaxel protein-bound
particles; albumin-bound
(Abraxane)

IV

Treatment of metastatic breast


cancer after failure of combination chemotherapy or relapse
within 6 months
of adjuvant therapy and NSCLC

Dose-limiting toxicity: Myelosuppression


Sensory neuropathy, myalgia, arthralgia, nausea, vomiting, diarrhea, mucositis, alopecia

Drug is free of solvents; therefore, no premedication is required to prevent hypersensitivity reactions.


Consider dose reduction by about 20% for severe sensory neuropathy; resume treatment
with reduced dose when neuropathy improves
to grade 1 or 2 (Solimando, 2008).
Do not use in patients with baseline neutrophil
count < 1,500 cells/mm3.
(Celgene Corp., 2012a)

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 7. Characteristics of Chemotherapeutic Agents (Continued)


Classification
Plant alkaloids (vinca
alkaloids)

Mechanism
of Action
Act in late G2
phase, blocking
DNA production,
and in M phase,
preventing cell
division

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

IV

Testicular cancer,
HL, Kaposi sarcoma, histiocytosis, NHL, breast
cancer

Dose-limiting toxicities: Myelosuppression, neurotoxicity


Alopecia, anorexia, jaw pain, peripheral neuropathy, constipation, paralytic ileus

Vinblastine is a vesicant.
Drug is fatal if given intrathecally.
Generally, neurotoxicity occurs less frequently
with vinblastine than with vincristine; however, it
is rare and usually reversible.
(Bedford Laboratories, 2010d)

Vincristine
(Oncovin)

IV

ALL, HL, NHL,


neuroblastoma,
Wilms tumor,
rhabdomyosarcoma

Dose-limiting toxicity: Neurotoxicity


Alopecia, peripheral neuropathy, constipation, paralytic ileus, jaw pain, foot
drop, renal and hepatotoxicity

Vincristine is a vesicant.
Drug is fatal if given intrathecally.
Neurotoxicity is cumulative, but often reversible; conduct a neurologic evaluation before
each dose. Withhold dose if severe paresthesia, motor weakness, or other abnormality develops.
Reduce dose in the presence of significant liver disease.
Stool softeners and/or a stimulant laxative may
help to prevent severe constipation.
(Hospira, Inc., 2011c)

Vinorelbine
(Navelbine)

IV

NSCLC

Dose-limiting toxicity: Myelosuppression


Nausea, vomiting, neurotoxicity, peripheral neuropathy, alopecia, hepatotoxicity

Do not use in pediatric patients.


Vinorelbine is a vesicant.
Flush with 75125 ml solution after completion of
vinorelbine administration.
Drug is fatal if given intrathecally.
(Teva Parenteral Medicines, Inc., 2009b)

AIDSacquired immunodeficiency syndrome; ALLacute lymphocytic leukemia; AMLacute myeloid leukemia; ANLLacute nonlymphocytic leukemia; APLacute promyelocytic leukemia; AUCarea under the
plasma concentration versus time curve; BCGbacillus Calmette-Gurin; BIDtwice daily; BMTbone marrow transplantation; CBCcomplete blood count; CLLchronic lymphocytic leukemia; CMLchronic myeloid leukemia; CNScentral nervous system; D5W5% dextrose in water; dldeciliter; DNAdeoxyribonucleic acid; ECGelectrocardiogram; FDAU.S. Food and Drug Administration; 5-FU5-fluorouracil; G2
gap 2; GIgastrointestinal; HDAChistone deacetylases; HLHodgkin lymphoma; IMintramuscular; INRinternational normalized ratio; ITintrathecal; IVintravenous; kgkilogram; LFTliver function test;
LRlactated Ringers solution; LVEFleft ventricular ejection fraction; Mmitosis; mcgmicrogram; MDSmyelodysplastic syndrome; mEqmilliequivalent; mgmilligram; minminute; mlmilliliter; MMmultiple myeloma; mmolmillimole; msecmillisecond; MUGAmultigated acquisition; NHLnon-Hodgkin lymphoma; NSnormal saline; NSAIDnonsteroidal anti-inflammatory drug; NSCLCnon-small cell lung cancer; PCPPneumocystis jiroveci pneumonia; PFTpulmonary function test; POby mouth; PTprothrombin time; PVCpolyvinyl chloride; QTcQT interval corrected; RNAribonucleic acid; Ssynthesis; SC
subcutaneous; SCLCsmall cell lung cancer; SCrserum creatinine; SIADHsyndrome of inappropriate antidiuretic hormone; TKItyrosine kinase inhibitor; TLStumor lysis syndrome; ULNupper limit of normal;
WBCwhite blood cell

47

Note. Based on information from Aronoff et al., 2007; Ascherman et al., 2000; Bragalone, 2012; Chu & DeVita, 2010; Elsevier/Gold Standard, 2013; Micromedex, 2013; Solimando, 2008; and manufacturers prescribing
information.

Chapter 3. Principles of Antineoplastic Therapy

Vinblastine
(Velban)

48

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

a) Cell cyclenonspecific drugs are effective in treating tumors with


more slowly dividing cells.
b) If the cancer is sensitive to the agent used, the drug is incorporated
into the cell. The cell kill may not be instantaneous but may occur
when the cell attempts to divide.
(1) Destruction of tumor cells is directly proportional to the amount
of drug administered.
(2) These drugs are given intermittently, allowing the individual to
recover from dose-limiting toxicities before the drug is repeated.
(3) The most frequent dose-limiting toxicity is bone marrow suppression.
c) Classifications include alkylating agents, antitumor antibiotics, hormonal therapies, and nitrosoureas.

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Bristol-Myers Squibb Co. (2011d). Taxol (paclitaxel) [Package insert]. Princeton, NJ: Author.
Bristol-Myers Squibb Co. (2011e). Vumon (teniposide injection) [Package insert]. Princeton, NJ: Author.
Brown, D. (in press). Cellular mechanisms of chemotherapy. In M.M. Gullatte (Ed.), Clinical guide
to antineoplastic therapy: A chemotherapy handbook (3rd ed.). Pittsburgh, PA: Oncology Nursing Society.
BTG International Inc. (2013). Voraxaze (glucarpidase) [Package insert]. Brentwood, TN: Author.
Celgene Corp. (2012a). Abraxane (paclitaxel protein-bound particles for injectable suspension) [Package insert]. Summit, NJ: Author.
Celgene Corp. (2012b). Vidaza (azacitidine) [Package insert]. Summit, NJ: Author.
Celgene Corp. (2013). Istodax kit (romidepsin) [Package insert]. Summit, NJ: Author.
Centocor Ortho Biotech Products, L.P. (2012). Leustatin (cladribine) [Package insert]. Raritan, NJ:
Author.
Cephalon, Inc. (2010). Trisenox (arsenic trioxide) [Package insert]. Frazer, PA: Author.
Cephalon, Inc. (2012). Treanda (bendamustine HCl) [Package insert]. Frazer, PA: Author.
Chu, E., & DeVita, V.T., Jr. (2010). Physicians cancer chemotherapy drug manual 2010. Burlington, MA:
Jones and Bartlett.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 3. Principles of Antineoplastic Therapy


Eisai Inc. (2009). Hexalen (altretamine) [Package insert]. Woodcliff Lake, NJ: Author.
Eisai Inc. (2010a). Dacogen (decitabine for injection) [Package insert]. Woodcliff Lake, NJ: Author.
Eisai Inc. (2010b). Halaven (eribulin mesylate) [Package insert] Woodcliff Lake, NJ: Author.
Eli Lilly and Co. (2011). Gemzar (gemcitabine for injection) [Package insert]. Indianapolis, IN: Author.
Eli Lilly and Co. (2013). Alimta (pemetrexed for injection) [Package insert]. Indianapolis, IN: Author.
Elsevier/Gold Standard. (2013). Clinical pharmacology [Online drug compendium]. Retrieved from
http://www.clinicalpharmacology.com
EMD Serono, Inc. (2010). Novantrone (mitoxantrone) [Package insert]. Rockland, MA: Author.
Endo Pharmaceuticals Solutions Inc. (2012). Valstar (valrubicin) [Package insert]. Chadds Ford, PA:
Author.
EUSA Pharma (USA), Inc. (2011). Erwinaze (asparaginase Erwinia chrysanthemi) [Package insert].
Langhorne, PA: Author.
Gate Pharmaceuticals. (2011). Purinethol (mercaptopurine) [Package insert]. Sellersville, PA: Author.
Genentech, Inc. (2010). Xeloda (capecitabine) [Package insert]. South San Francisco, CA: Author.
Genzyme Corp. (2013). Clolar (clofarabine injection) [Package insert]. Cambridge, MA: Author.
Gilead Sciences. (2011). DaunoXome (daunorubicin citrate liposome injection) [Package insert]. San Dimas, CA: Author.
GlaxoSmithKline. (2004). Leukeran (chlorambucil) [Package insert]. Research Triangle Park, NC: Author.
GlaxoSmithKline. (2008). Tabloid (thioguanine) [Package insert]. Research Triangle Park, NC: Author.
GlaxoSmithKline. (2009). Hycamtin (topotecan hydrochloride) [Package insert]. Research Triangle
Park, NC: Author.
GlaxoSmithKline. (2011a). Alkeran (melphalan) [Package insert]. Research Triangle Park, NC: Author.
GlaxoSmithKline. (2011b). Arranon (nelarabine) [Package insert]. Research Triangle Park, NC: Author.
Hande, K.R. (2009). Principles and pharmacology of chemotherapy. In J.P. Greer, J. Foerster, G.M.
Rodgers, F. Paraskevas, B. Glader, D.A. Arber, & R.T. Means Jr. (Eds.), Wintrobes clinical hematology (12th ed., pp. 16941720). Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams &
Wilkins.
Hospira, Inc. (2011a). Irinotecan [Package insert]. Lake Forest, IL: Author.
Hospira, Inc. (2011b). Methotrexate [Package insert]. Lake Forest, IL: Author.
Hospira, Inc. (2011c). Vincristine [Package insert]. Lake Forest, IL: Author.
Janssen Products, LP. (2013). Doxil (doxorubicin) [Package insert]. Horsham, PA: Author.
Lilleby, K., Garcia, P., Gooley, T., McDonnell, P., Taber, R., Holmberg, L., Bensinger, W. (2006). A
prospective, randomized study of cryotherapy during administration of high-dose melphalan to
decrease the severity and duration of oral mucositis in patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation. Bone Marrow Transplantation, 37, 1031
1035. doi:10.1038/sj.bmt.1705384
Loprinzi, C., Qin, R., Dakhil, S.R., Fehrenbacher, L., Stella, P.J., Atherton, P.J. ... Grothey, A. (2013).
Phase III randomized, placebo (PL)-controlled, double-blind study of intravenous calcium/magnesium (CaMg) to prevent oxaliplatin-induced sensory neurotoxicity (sNT), N08CB: An Alliance
for Clinical Trials in Oncology study. Journal of Clinical Oncology, 31(Suppl. 15), Abstract 3501.
Lundbeck. (2013). Elspar (asparaginase) [Package insert]. Deerfield, IL: Author.
Malumbres, M. (2007). Cyclins and related kinases in cancer cells. Journal of the Balkan Union of Oncology, 12(Suppl. 1), S45S52.
Merck & Co., Inc. (2009). Zolinza (vorinostat) [Package insert]. Whitehouse Station, NJ: Author.
Merck & Co., Inc. (2013). Temodar (temozolomide) [Package insert]. Whitehouse Station, NJ: Author.
Micromedex. (2013). Micromedex 2.0. Retrieved from http://www.micromedex.com/2/home
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Otto, S.E. (2007). Chemotherapy. In M.E. Langhorne, J.S. Fulton, & S.E. Otto (Eds.), Oncology nursing (5th ed., pp. 362376). St. Louis, MO: Elsevier Mosby.
Ovation Pharmaceuticals. (2008). Cosmegen (dactinomycin) [Package insert]. Deerfield, IL: Author.
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Pharmacotherapy, 40, 299303. doi:10.1345/aph.1G114
PDL BioPharma, Inc. (2007). Busulfan [Package insert]. Redwood City, CA: Author.
Pfizer Inc. (2010). Doxorubicin hydrochloride for injection, USP [Package insert]. New York, NY: Author.
Pfizer Inc. (2011). Ellence (epirubicin hydrochloride) [Package insert]. New York, NY: Author.
sanofi-aventis U.S. LLC. (2010). Taxotere (docetaxel for injection) [Package insert]. Bridgewater, NJ: Author.
sanofi-aventis U.S. LLC. (2011). Eloxatin (oxaliplatin) [Package insert]. Bridgewater, NJ: Author.
sanofi-aventis U.S. LLC. (2012). Jevtana (cabazitaxel) [Package insert]. Bridgewater, NJ: Author.
Sicor Pharmaceuticals. (2006). Zanosar (streptozocin) [Package insert]. Irvine, CA: Author.
Sigma-Tau Pharmaceuticals, Inc. (2011a). DepoCyt (cytarabine liposome injection) [Package insert].
Gaithersburg, MD: Author.
Sigma-Tau Pharmaceuticals, Inc. (2011b). Oncaspar (pegaspargase) [Package insert]. Gaithersburg,
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Sigma-Tau Pharmaceuticals, Inc. (2012). Matulane (procarbazine hydrochloride) [Package insert]. Gaithersburg, MD: Author.
Solimando, D.A., Jr. (Ed.). (2008). Drug information handbook for oncology: A complete guide to combination
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-0475
Teva Parenteral Medicines, Inc. (2007). Dacarbazine [Package insert]. Irvine, CA: Author.
Teva Parenteral Medicines, Inc. (2009a). Idarubicin [Package insert]. Irvine, CA: Author.
Teva Parenteral Medicines, Inc. (2009b). Vinorelbine [Package insert]. Irvine, CA: Author.
Teva Parenteral Medicines, Inc. (2011). Fludarabine [Package insert]. Irvine, CA: Author.
Teva Parenteral Medicines, Inc. (2012). Fluorouracil [Package insert]. Irvine, CA: Author.
Teva Pharmaceuticals USA, Inc. (2012). Synribo (omacetaxine mepesuccinate) [Package insert]. North
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doi:10.1002/path.3022

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 4

Principles of Biotherapy
A. Immunology: It is essential to understand the immune system in order to understand how biotherapy works. The immune system (see Figure 3) is a highly specialized and adaptive system that protects an individual by providing
1. Defense against foreign organisms
2. Homeostasis: Destruction of aging or damaged cells
3. Surveillance: Identification of foreign, or nonself, substances.
B. Types of immune response (Medzhitov, 2008; Muehlbauer, 2011; Paul, 2008):
An immune response is the reaction of the immune system against a foreign substance, or antigen (e.g., bacteria). Two types of immune responses exist (see Table 8).
1. Innate, or nonspecific, immunity (see Figure 4): Essential for inducing a generic immune response to antigens (Janeway, Travers, Walport,
& Shlomchik, 2005). Innate immunity does not generate immunologic
memory and involves the following (Medzhitov, 2008).
Figure 3. Primary and Secondary Lymphoid Organs

Tonsils and
adenoids

Thymus

Lymph
nodes
Spleen

Appendix

Peyers
patches

Lymph
nodes

Lymphatic
vessels
Bone
marrow

51
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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

a) Physical barriers (skin and mucous membranes)


b) Mechanical barriers (coughing, sneezing, and blinking)
c) Chemical barriers (tears and sweat)
d) Inflammatory responses (production of monocytes, macrophages,
and polymorphonuclear cells)
e) Complement activation
f) Acute-phase protein production (e.g., interleukin [IL]-2)
g) Production of large granular lymphocytes (natural killer [NK] or NK
and natural killer T [NKT] cells)
2. Adaptive, or specific, immunity: Secondary line of defense and involves
immunologic memory, specificity, and collaboration of B cells and T
cells (McHeyzer-Williams, 2008). The three types of adaptive immunity are the following.

Table 8. Innate and Adaptive Immune Responses


Immune
Response

Mechanism of Action

Cells Primarily Involved

Innate

Primary line of defense


Nonspecific
No memory

Neutrophils
Monocytes, macrophages
Large granular lymphocytes (natural killer
cells)

Adaptive

Secondary line of defense


Specific memory

Lymphocytes
T cells (in cell-mediated immunity)
B cells (in humoral immunity)

Note. Based on information from Paul, 2008.

Figure 4. Innate (Nonspecific) Immune Response

gu

lf

Lyse

Natural killer cells

Phagocytes
Tumor cells

En

52

Polymorphonuclear
leukocytes

Monocytes

Macrophages
Eng

ulf

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Chapter 4. Principles of Biotherapy

a) Humoral immunity (see Figure 5): B lymphocytes, memory B cells,


and plasma cells mediate humoral immunity. The result is the production of immunoglobulins (Igs).
b) Cell-mediated immunity (see Figure 6): This type of immunity is mediated by T cells and their cytokine products. It does not involve an
antibody but rather cytotoxic T cells (TC) and helper T cells (TH1 or
TH2) (Reiner, 2008).
c) Regulatory T cells (Treg), also known as suppressor T cells (TS)
(1) Limit the activity of other immune effector cells.
Figure 5. Adaptive (Specific) Immune Response: B Cells and Humoral Immunity

Figure 6. Adaptive (Specific) Immune Response: Cell-Mediated Immunity

T-cell activation

Activated cytotoxic T cell kills foreign


cells, virally infected cells, or cells
with new surface antigens.

Activated helper T cell produces


cytokines.

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(2) Their major role is thought to be to prevent the onset of immunity to normal tissues of the body and limit the inflammatory response that can occur with infections.
(3) Animals and people without Treg cells develop a variety of inflammatory disorders primarily involving the bowel, skin, and liver.
C. Cells of the immune system (see Figure 7): The immune response involves the intricate interaction of a number of cells and proteins (PostWhite & Bauer-Wu, 2011). Many cells of the immune system express cluster of differentiation (CD) markers on their surfaces. These CD markers
(e.g., CD4, CD20) are associated with certain immune functions. The science behind biotherapy has capitalized on the use of CD markers to create cell-specific therapy.
1. Antigen-presenting cells: Cells (e.g., macrophages, B cells, dendritic
cells) that efficiently present antigen to T cells; only dendritic cells are
capable of initiating a primary immune response.
2. T cells (Lesterhuis, Haanen, & Punt, 2011; Pardoll, 2012; Paul, 2008;
Reiner, 2008; Restifo, Robbins, & Rosenberg, 2008)
a) TH cells: Cells that coordinate the immune response and cell-mediated immunity; they are required to maintain cytotoxic T cell responses and express CD4.
(1) TH1 cells are necessary for activating macrophages and are involved in production of certain antibody isotypes.
(2) TH2 cells are effective activators of B cells, particularly in primary responses.
b) TC cells: Cells that kill foreign cells, virally infected cells, or cells with
new surface antigens. TC cells express CD8.
c) Treg/TS cells: Cells that interfere with development of immune reaction when recognizing antigen. Their primary role is to modulate the
severity of inflammation produced by infection and prevent autoimmunity; they may be involved in malignancy.
d) Memory T cells (TM cells): Cells that recognize specific antigens and
induce recall responses
e) Cytotoxic T-lymphocyte antigen 4 (CTLA-4): Part of a group of molecules that contribute to activation or inhibition of T-cell immune re-

Figure 7. Cells of the Immune System

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 4. Principles of Biotherapy

sponses (i.e., it is an immune checkpoint). The consequence of CTLA4 ligands binding on antigen-presenting cells is a negative regulation
of T-cell activity. CTLA-4 expression decreases the activation of T cells
as well as sending inhibitory signals to the T cell. CTLA-4 is expressed
by activated CD8+ cells, but the primary role of CTLA-4 is diminishing
TH activity and enhancing Treg immunosuppressive activity.
3. NK cells: Cells that are cytotoxic to tumor cells and virally infected autologous cells by producing substances that can bind to and destroy foreign invaders without having to identify a specific antigen. NK cells identify foreign substances by their lack of identifying surface molecules.
4. NKT cells: Cells that have markers both of NK cells and T cells
5. B lymphocytes: Plasma cell precursors; plasma cells manufacture Ig (an
antibody) specific to an initiating antigen.
6. Antibodies: Protein products of plasma cells; also known as immunoglobulins, they enhance effector cell functions.
a) The majority of peripheral blood antibodies are IgG, which enhances phagocytosis of antigen by macrophages, monocytes, polymorphonuclear cells, and some lymphocytes.
b) IgM is the first antibody produced in response to an antigen.
c) IgA is present in bodily secretions and helps to prevent infections
at sites where the environment interacts with the body, such as the
nose and lungs.
d) IgD is present in small amounts in normal serum. The exact biologic
function is unclear; however, IgD may have some antibody function
for penicillin, diphtheria, and insulin.
e) IgE exists in trace amounts in normal serum and is associated with
immediate hypersensitivity reactions. IgE antibodies are generated
when combined with certain antigens, thus activating the release of
histamine from mast cells.
7. Cytokines: Glycoprotein products of immune cells such as lymphocytes
and macrophages. Cytokines are produced in response to T-cell activation. Cytokines mediate effector defense functions. Cytokines themselves
usually are not cytotoxic (e.g., ILs, interferon [IFN]).
8. Chemokines: Known as chemotactic cytokines, these protein molecules regulate leukocyte migration and are key organizers of cell distribution in
both immune and inflammatory responses.
D. Tumor escape mechanisms: When immune surveillance fails, tumor formation occurs. The theories to explain this process include the following (Agarwal & Busse, 2010; Demaria et al., 2010; Liu, 2011; Muehlbauer, 2011; Topalian, Weiner, & Pardoll, 2011).
1. Altered immunogenicity: Tumors are targeted by the immune system
through cell surface molecules that function as targets for antibody responses or by intracellular molecules that are presented within the context of the major histocompatibility complex (MHC) molecules.
a) Altered antigen expression on the tumor cell surface allows the antigen to go unrecognized by the humoral immune system.
b) Cell-mediated immune response is blunted through loss or alteration
of MHC molecules or loss or mutation of the peptide epitope that
binds to the MHC molecule and is recognized by T cells.
2. Antigen modulation: Antibodies produced as part of the immune response cause antigens to enter the tumor cell or leave it completely.
This further limits the ability of the immune cells to recognize the tumor cell as nonself.
3. Immune suppression: The tumor itself produces substances that alter
or inhibit the bodys immune response. One example is transforming
growth factor-beta, which inhibits T-cell activity.
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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

4. Acquired deficiencies to immune sensitivity: These include age- and disease-associated alterations such as decreased or increased apoptosis and
signaling defects of T cells.
5. Immunologic aging or immunosenescence: Causes decline in numbers of
nave T cells, generation of TC cells, hematopoietic stem cells, phagocytes,
and NK cells, production of IL-2, signal transduction of lymphocytes, and
humoral immunity. There is also decreased antigen response and proliferation, increased TM cells, and potentially decreased functional Treg cells.
6. Tumors fail to give off inflammatory warning signals to stimulate an immune response.
E. Overview of biologic therapies
1. NCI defines biotherapy as treatment to boost or restore the ability of the
immune system to fight cancer, infections, and other diseases. It also is
used to lessen certain side effects that may be caused by some cancer
treatments. Agents used in biotherapy include mAbs, growth factors, and
vaccines (Biotherapy, n.d.).
2. Theory of immune surveillance
a) The transformation of a cell from normal to malignant involves a
number of genetic mutations over a span of years.
b) As cells differentiate, they produce proteins (antigens) on their surface
that the immune system recognizes as nonself; an immune response
can be mounted in defense. However, cells may not always recognize
cancer cells as foreign (Koon & McDermott, 2011; Restifo et al., 2008).
3. Methods of action: Biotherapeutic agents work by doing one or more of
the following (Koon & McDermott, 2011).
a) Enhancing the patients own immune response
b) Altering the milieu in which cancer cells grow by modifying the actions of normal cells in the area of the tumor
c) Increasing the vulnerability of cancer cells to the bodys own immune system
d) Altering the pathway by which normal cells transform into malignant
cells, which may be more preventive than therapeutic
e) Preventing the metastasis of cancer cells
f) Enhancing the repair of normal cells damaged by treatment
g) Changing cancer cells so they behave like healthy cells
F. Categories of biotherapy (Koon & McDermott, 2011; Muehlbauer, 2011)
1. Cytokines
a) Cytokines are small protein molecules released by diverse cells throughout the body, providing communication between the cells of the immune system.
b) Cytokines generally are activated by a stimulus and induce responses
by binding to specific receptors. Cells expressing receptors for specific cytokines can be activated or inhibited, either of which alters the
immune effector function.
c) Cytokines affect the growth and differentiation of WBCs and regulate immune and inflammatory responses.
d) Cytokines may enhance cytotoxic activity and secrete additional cytokines, resulting in amplification of immune response. This enhanced
immune response stimulates proliferation or activation and recruitment of additional immune effector cells.
e) Cytokines are multifunctional substances having proinflammatory,
anti-inflammatory, and regulatory functions in the immune system.
f) Cytokines include a variety of ILs, IFNs, tumor necrosis factors (TNFs),
and transforming growth factor. Examples include IL-1, -2, -3, -4, -6,
-8, -10, and -15 and IFN- and IFN-.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 4. Principles of Biotherapy

g) Cytokines regulate antibody production and the functions of B and


T cells, as well as interact with antigen-presenting cells and NK cells.
h) Examples of cytokines used for therapeutic purposes
(1) Hematopoietic growth factors
(2) IFNs
(3) ILs
2. mAbs (see Figure 8 for nomenclature) (Muehlbauer, Cusack, & Morris,
2006; Scheinberg, Rosenblat, Jurcic, Sgouros, & Junghans, 2011; Wujcik, 2011)
a) General
(1) A type of targeted biotherapy derived from human antibodies,
mouse antibodies, or combinations thereof
(a) Murine: Derived from mouse antibody; less effective because they lack the ability to bind to the Fc receptor
(b) Chimeric: Combination of mouse and human antibodies
(c) Humanized: Small part mouse antibodies fused with human antibodies
(d) Human: Only human antibodies
(2) Cell surface proteins can function as targets for binding mAbs.
(3) mAbs target host tissues or proteins that support tumor growth,
such as growth factors and growth factor receptors, or they may
identify targets that are relatively unique to the tumor cell population.

Figure 8. Types of Monoclonal Antibodies

Comparison of monoclonal antibodies (brown: human, gray: nonhuman):


Top row: mouse, chimeric
Bottom row: humanized, chimeric/humanized, human
The substems according to the nomenclature of monoclonal antibodies are shown below each
antibody.
Note. Public domain image from Wikimedia Commons. Retrieved from http://en.wikipedia.org/wiki/
File:Chimeric_and_humanized_antibodies.svg.

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(4) mAbs may inhibit the binding of growth factors to their respective receptors on the cell surface and shut off downstream signaling that stimulates tumor cell growth.
(5) Antibodies recognize and bind to specific antigens.
(a) Depending on its particular class and subtype, an antibody
can interact with other serum proteins, such as the complement system or Fc receptors on cells, to activate normal
immune functions that selectively eliminate the antigen or
the target cell expressing that antigen.
(b) Antibody-dependent cellular cytotoxicity is thought to be
the major mechanism for response to most mAbs. It is believed to involve a three-step process:
i. The antibody binds to the antigen of the tumor cell.
An example is rituximab, which is anti-CD20 and binds
to CD20 receptors on lymphocytes.
ii. NK cells recognize the antibody-covered tumor cells.
iii. Cytotoxic proteins are released to destroy tumor cells.
(c) Alternatively, mAbs can act directly on the tumor cell to induce cell death.
b) Unconjugated antibodies: Antitumor activity results solely from the
actions of the mAb on its targets. These mAbs do not have cytotoxic
agents or radioisotopes attached to them (Muehlbauer et al., 2006;
Scheinberg et al., 2011). Examples include
(1) Rituximab (targets CD20)
(2) Trastuzumab (targets human epidermal growth factor receptor 2 [HER2])
(3) Cetuximab (targets EGFR)
(4) Bevacizumab (targets vascular endothelial growth factor [VEGF])
(5) Ipilimumab (targets anti-CTLA-4)
c) Conjugated antibodies: Antibodies are physically attached to antitumor agents such as radioisotopes (through RIT), chemotherapy
drugs, toxins, or other biologic agents.
(1) After targeting specific antigens, conjugated mAbs release the
attached antitumor agent into the cells or deliver high levels of local radioactive emissions to the site. An example of a
conjugated mAb is brentuximab vedotin, currently FDA approved for the treatment of HL and systemic anaplastic largecell lymphoma.
(2) An advantage of RIT is its ability to kill cells at a distance with
no need to bind to tumor cells directly to have beneficial effects.
(3) Examples of radioisotope conjugates (antibodies labeled with
a radioisotope)
(a) Ibritumomab tiuxetan (Zevalin) (Spectrum Pharmaceuticals, Inc., 2011)
(b) Iodine-131 tositumomab (Bexxar) (GlaxoSmithKline, 2012a)
G. RIT (Iwamoto, Haas, & Gosselin, 2012; Sharkey & Goldenberg, 2011)
1. RIT is a radiopharmaceutical cancer treatment that employs radionuclide-labeled, or radiolabeled, mAbs. These antibodies, which are administered systemically by intravenous (IV) injection, recognize tumor-associated antigens to deliver radioactivity to tumor cells selectively.
2. The goal of RIT is to destroy or inactivate cancer cells while preserving
the integrity of normal tissues.
3. Each radionuclide emits radiation particles and/or rays with energies
that are characteristic of that specific radionuclide. Depending on its
type, a radionuclide can emit one, two, or three types of emissions (Iwamoto et al., 2012; Sharkey & Goldenberg, 2011).
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 4. Principles of Biotherapy

a) Alpha particles
(1) Consist of two protons and two neutrons (the nucleus of a helium atom)
(2) These particles have poor penetrating ability. Alpha particles
cannot penetrate the outermost layers of skin, and they travel
a maximum distance of 5 cm.
(3) A sheet of paper is sufficient to block the radiation source, or
a distance of 5 cm between the radiation source and the point
will shield the radiation.
(4) The skin of an alpha-irradiated patient is adequate to protect
others from radiation exposure; in other words, alpha particles
are not external hazards, but ingestion or inhalation can be lethal or produce secondary malignancies.
(5) Contact with an irradiated patients excreted body fluids may
be hazardous. The use of universal precautions is sufficient.
b) Beta particles
(1) Are electrons
(2) Have greater penetration abilities than do alpha particles and thus
have great potential to cause severe myelosuppression in a patient
(3) Like alpha particles, beta particles are not external hazards.
The patients skin or thick plastic shielding usually is adequate
protection from beta particles.
(4) Yttrium-90 (such as Zevalin) emits beta particles (Spectrum
Pharmaceuticals, Inc., 2011).
(5) After RIT
(a) The patients body fluids are temporarily radioactive.
(b) The patient should receive specific discharge instructions
to limit family exposure.
c) Gamma rays
(1) Are high-energy gamma-emitting radionuclides
(2) Protection from these rays is achieved by maintaining a specific distance from the radioactive source (the distance is specific to the radioisotope used) and using appropriate shielding.
(3) Patients receiving this type of radionuclide may have to be in radiation isolation and behind lead shields (Iwamoto et al., 2012).
(4) Iodine-131 emits high-energy beta particles and gamma rays.
The thyroid gland concentrates iodine and is at risk of damage
if radioactive iodine is ingested.
4. Toxin-conjugated molecules
a) Toxins such as diphtheria or Pseudomonas exotoxin are potent inhibitors
of cell viability. One molecule of diphtheria toxin delivered intracellularly is capable of inhibiting protein synthesis that results in cell death.
b) Antibodies and cytokines deliver these toxic molecules to cancer cells,
and cell death depends upon their uptake of them.
c) The strategy of delivering toxins intracellularly has resulted in FDA
approval of agents for the treatment of malignancy, for example, denileukin diftitox for the treatment of persistent or recurrent CD25+
cutaneous T-cell lymphoma (NCI, 2013).
5. Vaccines
a) The goal of cancer vaccines is to harness the immune system to fight or
destroy the tumor. Theoretically, this can be achieved by the following
methods (Hammerstrom, Cauley, Atkinson, & Sharma, 2011; Liu, 2011).
(1) Protection against pathogens that can cause cancer
(2) Via immunosurveillance, where the body recognizes and destroys cancer cells prior to their multiplying and giving rise to
clinically observable cancer
(3) Immunostimulation
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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

b) Two vaccines for cancer prevention are FDA approved.


(1) Hepatitis B vaccine: Hepatitis B viral infection can lead to hepatocellular carcinoma. This vaccine prevents hepatitis as well
as hepatocellular carcinoma.
(2) HPV vaccine (Cervarix and Gardasil): Infection with certain
strains of HPV has been associated with development of several cancers including cervical, anal, penile, and head and neck.
Gardasil protects against HPV types 6, 11, 16, and 18 (Merck &
Co., Inc., 2011). Cervarix protects against HPV types 16 and 18
(GlaxoSmithKline, 2011b).
(3) Most vaccines for cancer treatment are experimental, and results
have been disappointing. One vaccine is FDA approved for cancer treatment: sipuleucel-T (Provenge) for advanced prostate
cancer. It is an autologous cellular immunotherapy containing
CD54+ cells designed to induce an immune response against
a common prostate cancer antigen (Dendreon Corp., 2011).
H. Therapeutic uses for biotherapeutic agents (see Table 9): Biotherapeutic
agents have been shown to
1. Cure, when used as a primary or adjuvant therapy
2. Improve overall response or increase disease-free survival when used in
conjunction with conventional therapies (Koon & McDermott, 2011;
Oldham, 2009)
3. Control or stabilize disease
4. Maintain or enhance QOL.
I. Supportive uses for biotherapeutic agents: Biotherapeutic agents can decrease the severity of toxicities associated with other therapeutic modalities (e.g., hematopoietic growth factors can lessen the side effects of chemotherapy).
J. Biotherapeutic strategies: Advances in the knowledge of molecular biology
have led to the development of agents referred to as targeted therapies. These
agents are divided into those that target the extracellular, such as receptors
on the cell surface (e.g., mAbs), and those that target intracellular processes. A growing number of unique molecular targets have been identified within cancer cells, resulting in the discovery of novel agents, many of which are
oral. See Table 10 for a list of targeted therapies.
1. Signal transduction and targeted therapies (Bafico, Grumolato, & Aaronson, 2008; Clark, 2011; Pawson & Jorgensen, 2008; Wilkes, 2006;
Wilkes, Esper, & Muehlbauer, 2006; Wujcik, 2011) (See Figure 9 for common terminology.)
a) Cellular growth, function, and apoptosis are regulated by a complex
network of biochemical and molecular messengers. This process is
referred to as cell signaling.
b) Signal transduction is the generation of a signal from either outside
the cell (growth factors and growth factor receptors) or inside the
cell (tyrosine kinase receptors) that produces a signaling cascade to
the cell nucleus and delivers a signal for the cell to divide.
(1) The nucleus then directs the cell activities. This could include
cell proliferation, induction of angiogenesis, increased growth
factor production, or inhibition of apoptosis.
(2) Receptor tyrosine kinases contain several domains, including an
extracellular ligand-binding domain, a transmembrane domain,
and an intracellular domain containing protein tyrosine kinase.
(3) Activation of receptor tyrosine kinases triggers a biochemical
cascade of cell-signaling events. This signal transduction can
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 9. Characteristics of Biologic Agents


Classification
Colonystimulating
factors

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Darbepoetin
(Aranesp)

SC

Treatment of anemia associated with


chronic renal failure, whether or not
the patient is receiving dialysis
Treatment of anemia in patients with
nonmyeloid malignancies where anemia is caused by concomitantly administered chemotherapy and at least
two additional months of chemotherapy is planned

Hypertension, skin
rash, urticaria, pure
red cell aplasia, myalgia, infection, fatigue, edema, diarrhea, thrombotic
events

Risk of death, stroke, thrombosis, and serious


cardiovascular events is increased if Hgb >
11 g/dl when administered.
Ensure adequate iron stores in patients prior to and during use.
Drug may be administered every 1, 2, or
3 weeks, but maintain consistent dosing
schedule.
Use lowest effective dose to avoid blood
transfusions.
Do not shake vials or syringes containing drug.
Store in refrigerator.
Do not freeze.
Prescribers and hospitals must enroll in the
ESA APPRISE Oncology Program.
Use is not indicated in patients in whom
cure is the anticipated outcome of chemotherapy treatment.
Discontinue use when treatment with chemotherapy is completed.
(Amgen, Inc., 2012a)

Stimulates erythropoiesis via the same


mechanism as endogenous erythropoietin

Epoetin alfa
(Procrit)

SC

Treatment of anemia associated with


chronic renal failure, whether or not
the patient is receiving dialysis
Treatment of zidovudine-associated
anemia in HIV-infected patients
Treatment of anemia in patients with
nonmyeloid malignancies where anemia is caused by concomitant use of
chemotherapy and at least two additional months of chemotherapy is
planned
To reduce the need for allogeneic red
blood cell transfusions in patients
scheduled to undergo elective noncardiac, nonvascular surgery

Hypertension, skin
rash, urticaria, pure
red cell aplasia, myalgia, infection, fatigue, edema, diarrhea, thrombotic
events

Risk of death, stroke, thrombosis, and serious


cardiovascular events is increased if Hgb >
11 g/dl when administered.
Ensure adequate iron stores in patients prior to and during use.
May be given 3 times weekly or as a single
weekly dose.
Use lowest effective dose to avoid blood
transfusions.
Do not shake vials or syringes containing drug.
Store in refrigerator.
Do not freeze.
Prescribers and hospitals must enroll in the
ESA APPRISE Oncology Program.
Use is not indicated in patients in whom
cure is the anticipated outcome of chemotherapy treatment.
Discontinue use when treatment with chemotherapy is completed.
(Janssen Products, LP, 2013)

61

(Continued on next page)

Chapter 4. Principles of Biotherapy

Stimulates erythropoiesis via the same


mechanism as endogenous erythropoietin

62

Table 9. Characteristics of Biologic Agents (Continued)

Colonystimulating
factors (cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Regulates the production of neutrophils within the bone


marrow

Filgrastim (GCSF, Neupogen)

SC, IV

To decrease the incidence of infection


in patients with neutropenic fever associated with myelosuppressive anticancer treatments for nonmyeloid malignancies
To reduce the time to neutrophil recovery and duration of fever following induction or consolidation chemotherapy in patients with AML
To reduce the duration of neutropenia
and associated sequelae in patients
receiving myeloablative chemotherapy prior to BMT
To mobilize hematopoietic progenitor
cells into peripheral blood for collection via leukapheresis
For chronic administration to reduce the
incidence and duration of sequelae of
neutropenia in patients with congenital, cyclic, or idiopathic neutropenia

Allergic reactions including urticaria, rash, and facial edema; rare


risk of splenic rupture; ARDS, alveolar hemorrhage and
hemoptysis, nausea,
vomiting, bone pain,
fever

Store in refrigerator.
Do not freeze.
Drug may be diluted with D5W.
Do not dilute with saline solutions.
Do not shake vials or syringes containing
drug.
Avoid use 24 hours before through 24 hours
after administration of chemotherapy; first
dose should be administered at least 24
hours after chemotherapy is administered.
(Amgen, Inc., 2013)

Human G-CSF;
binds to G-CSF receptors and stimulates proliferation of
neutrophils

Tbo-filgrastim
(Granix)

SC

Reduction in the duration of severe


neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia

Allergic reactions, risk


of splenic rupture,
ARDS, bone pain,
may induce severe
sickle-cell crisis in
patients with sicklecell disease

Administer with safety needle guard device.


Inject the entire dose in the prefilled syringe in order to activate the safety needle guard.
Store in refrigerator at 36F46F.
Avoid shaking.
Tbo-filgrastim should be clear without particles; inspect prior to administration.

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 9. Characteristics of Biologic Agents (Continued)


Classification
Colonystimulating
factors (cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Pegfilgrastim
(PEG-G-CSF;
Neulasta)

SC

To decrease the incidence of infection


related to neutropenia in patients with
nonmyeloid malignancies receiving
myelosuppressive chemotherapy

Allergic reactions including urticaria,


rash, facial edema;
rare risk of splenic
rupture; ARDS, nausea, vomiting, bone
pain, fever

Pegfilgrastim reduces renal clearance and


prolongs persistence compared to filgrastim.
Do not administer in the period beginning
14 days before until 24 hours after administration of myelosuppressive chemotherapy.
Administer as a single 6 mg injection once
per chemotherapy cycle.
Do not administer the 6 mg fixed dose to
children or adolescents weighing less
than 45 kg.
Store in refrigerator.
Do not freeze.
Do not shake vials or syringes containing
drug.
(Amgen, Inc., 2012b)

Stimulates keratinocyte GFR to result


in proliferation, differentiation, and migration of epithelial cells

Palifermin
(rHuKGF,
Kepivance)

IV

To decrease the incidence and duration


of severe oral mucositis in patients
with hematologic malignancies receiving myelosuppressive chemotherapy
prior to BMT

Skin rash, skin erythema, pruritus, fever,


dysesthesia, tongue
discoloration, tongue
thickening, taste alterations, pain, arthralgias, elevated
serum amylase, elevated serum lipase

Do not use within 24 hours before, during,


or after administration of myelosuppressive chemotherapy.
Administer for 3 days before and then 3
days after myelosuppressive chemotherapy.
The third dose should occur 2448 hours
prior to starting chemotherapy; the fourth
dose should be given on the day of hematopoietic stem cell infusion, after the
infusion is complete.
Do not shake reconstituted solution.
Protect reconstituted product from light
and do not use if stored at room temperature for longer than 1 hour.
Do not filter reconstituted solution.
(Amgen, Inc., 2009)

63

(Continued on next page)

Chapter 4. Principles of Biotherapy

Regulates the production of neutrophils within the bone


marrow

64

Table 9. Characteristics of Biologic Agents (Continued)


Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Colonystimulating
factors (cont.)

Induces committed progenitor cells


to divide and differentiate in the GM
pathways, including
neutrophils, monocytes/macrophages,
and myeloid-derived
dendritic cells

Sargramostim
(GM-CSF, Leukine)

SC, IV

Following induction chemotherapy in


patients with AML to shorten neutrophil recovery and reduce incidence of
infection.
For mobilization of hematopoietic progenitor cells for collection via leukapheresis and to speed engraftment
following autologous transplantation
of progenitor cells
To accelerate myeloid recovery following allogeneic BMT
In patients with failure of engraftment
following BMT

Edema, capillary leak


syndrome, pleural or
pericardial effusions,
dyspnea, fever, abdominal pain, headache, chills, diarrhea, bone pain

Dilute in NS solution for IV use.


Store in refrigerator.
Do not freeze.
Do not shake vials or syringes containing drug.
Do not administer through in-line filter.
(sanofi-aventis U.S. LLC, 2012)

Interferons
(IFNs)

Mechanisms of activity are not clearly understood but include inhibition of viral replication, direct antiproliferation
of tumor cells, and
modulation of host
immune response.

IFN alfa-2b
(Intron A)

SC, IM, IV

Treatment of hairy cell leukemia, malignant melanoma, follicular lymphoma,


condylomata acuminata, AIDS-related Kaposi sarcoma, chronic hepatitis B and C

Fever, chills, malaise,


myalgia, headache,
anorexia, fatigue,
depression, suicidal ideation, nausea, vomiting, diarrhea, nephrotic syndrome, pancreatitis, psychosis, hallucinations, renal failure, renal insufficiency, leukopenia, anemia, thrombocytopenia, retinopathy, thyroid abnormalities,
hepatotoxicity

Counsel patients on potential for side effects, including but not limited to flu-like
syndrome.
Store in refrigerator.
Do not freeze.
Do not shake product.
Protect from light.
Product in multidose vial is stable for 30
days after reconstitution when stored in
refrigerator.
Drug is contraindicated in patients with autoimmune hepatitis or decompensated
liver disease.
Use with caution in patients with a history
of debilitating medical disease such as
pulmonary disease, cardiovascular disease, diabetes mellitus, coagulation disorders, or severe myelosuppression.
Monitor triglycerides.
(Merck & Co., Inc., 2012)

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 9. Characteristics of Biologic Agents (Continued)


Classification

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Immunomodulatory effects including


enhancement of oxidative metabolism
of macrophages,
ADCC, activation
of NK cells, and expression of Fc receptors and cell surface antigens

IFN-gamma
(Actimmune)

SC

To reduce frequency and severity of infections related to chronic granulomatous disease


To delay progression of severe malignant osteoporosis

Fever, headache,
rash, chills, injectionsite tenderness, fatigue, diarrhea, vomiting, nausea, myalgia, arthralgia, myelosuppression, elevated hepatic transaminases, altered
mental status, gait
disturbance, dizziness

Hold therapy or reduce dose by 50% in


cases of severe reactions.
Flu-like syndrome may exacerbate preexisting cardiac conditions, such as CHF.
(InterMune, Inc., 2009)

Interleukins
(ILs)

Promotes proliferation, differentiation,


and recruitment of
T and B cells, NK
cells, LAK cells,
and tumor-infiltrating lymphocytes
that enhance tumorfighting capabilities;
increases production of IFN-gamma,
IL-1, and TNF

Aldesleukin (IL2, Proleukin)

SC, IV

Treatment of renal cell carcinoma and


metastatic melanoma

Fever, rigors, malaise,


headache, myalgia,
arthralgia, tachycardia, hypotension,
cardiomyopathy, arrhythmias, capillary
leak syndrome, dyspnea, nausea, vomiting, diarrhea, stomatitis, dizziness, anemia, thrombocytopenia, leukopenia, elevated transaminases, elevated serum
creatinine and BUN,
neurologic toxicities,
skin rash, pruritus,
hyperbilirubinemia

Do not use with an in-line filter.


Do not mix with NS or bacteriostatic water.
Store in refrigerator.
Do not freeze.
Protect from light.
Do not mix with other medications.
Monitor fluid status, vital signs, mental status, and urine output. Hypotension is
dose limiting and mimics septic shock;
use IV boluses carefully; treatment may
require vasopressor support.
Drug is contraindicated in patients with
cardiac disease, abnormal pulmonary
function, or organ allografts.
Assess fall risk during treatment.
May exacerbate or lead to initial presentation of autoimmune diseases or inflammatory disorders such as Crohn disease, scleroderma, thyroiditis, inflammatory arthritis, diabetes mellitus, and cholecystitis.
(Prometheus Laboratories Inc., 2012)

65

(Continued on next page)

Chapter 4. Principles of Biotherapy

Interferons
(IFNs) (cont.)

66

Table 9. Characteristics of Biologic Agents (Continued)


Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Interleukins
(ILs) (cont.)

Stimulates megakaryocytopoiesis
and thrombopoiesis

Oprelvekin (IL11, Neumega)

SC

To prevent severe thrombocytopenia and reduce the need for platelet


transfusions in patients with nonmyeloid malignancies receiving chemotherapy

Anaphylaxis, dilutional anemia, diarrhea,


dizziness, fever, fluid retention resulting
in peripheral edema,
pulmonary edema,
dyspnea, capillary
leak syndrome, atrial
arrhythmias and exacerbation of preexisting pulmonary effusions, headache,
nausea, vomiting, insomnia, rhinitis

Store in refrigerator.
Do not freeze.
Reconstitute with sterile water and use
within 3 hours of reconstitution.
Do not shake or freeze following reconstitution.
Protect from light.
Use with caution in patients with preexisting CHF or other conditions that may be
exacerbated by fluid retention.
Dosing should be initiated 624 hours after
completion of chemotherapy and discontinued at least 2 days before the start of
the next cycle of chemotherapy.
(Wyeth Pharmaceuticals, 2006)

Hematopoietic stem cell


mobilizers

Inhibits the CXCR4


receptor, which
competitively blocks
binding of SDF1-
ligand that anchors
developing hematopoietic stem cells
in the bone marrow,
resulting in release
into the peripheral blood

Plerixafor
(Mozobil)

SC

In combination with filgrastim to mobilize hematopoietic stem cells for collection from peripheral blood of patients with multiple myeloma or nonHodgkin lymphoma who are candidates for autologous stem cell transplantation

Diarrhea, nausea, fatigue, injection-site


reactions, headache,
dizziness, arthralgia,
vomiting

Use actual body weight to calculate dose;


daily dose should not exceed 40 mg.
Store single-use vials at room temperature.
Use reduced dose in patients with creatinine clearance < 50 ml/min.
Four daily morning doses of filgrastim
should be given prior to the first dose of
plerixafor.
Plerixafor may be repeated for up to 4 consecutive days.
Each daily dose of plerixafor should be given approximately 11 hours before any
planned apheresis session.
(Genzyme Corp., 2010)

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 9. Characteristics of Biologic Agents (Continued)


Classification
Autologous
cellular immunotherapy

Mechanism
of Action
Autologous CD54+
mononuclear cells
are collected from
the patient and activated in culture with
PAP-GM-CSF for
subsequent infusion.
The activated cells
are designed to induce an immune
response against
prostatic acid phosphatase antigen expressed in patients
with prostate cancer.

Drug
Sipuleucel-T
(Provenge)

Route of
Administration
IV

Side Effects

Nursing Considerations

Treatment of asymptomatic or minimally


symptomatic metastatic castrateresistant prostate cancer

Infusion reactions
such as fever, chills,
dyspnea, hypoxia,
bronchospasm, nausea, vomiting, fatigue, hypertension,
tachycardia, joint
ache, headache

Each dose is cellularly unique and for use


only in one individual patient.
The patients mononuclear cells are collected via apheresis 3 days prior to
planned infusion, shipped to the manufacturer for preparation of the infusion,
and then returned to the administration
site.
Confirmation of product release using patient-specific product disposition forms
must be performed prior to infusion.
Do not administer through a cell filter.
Premedicate patients with acetaminophen
and a histamine antagonist.
Employ universal precautions when handling sipuleucel-T.
Prepared infusion bag must remain within the insulated container until time of infusion.
Do not administer infusion if the storage
bag leaks or clumps remain after gentle mixing.
Once infusion product is removed from insulated storage, it should not remain
at room temperature for longer than 3
hours.
The 60-minute infusion must be completed
prior to expiration date and time.
(Dendreon Corp., 2011)

67

ADCCantibody-dependent cell-mediated cytotoxicity; AIDSacquired immunodeficiency syndrome; AMLacute myeloid leukemia; ARDSadult respiratory distress syndrome; BMTbone marrow transplantation;
BUNblood urea nitrogen; CD54+cluster of differentiation 54 positive; CHFcongestive heart failure; CXCR4chemokine receptor 4; D5W5% dextrose in water; ESAerythropoiesis-stimulating agent; G-CSF
granulocytecolony-stimulating factor; GFRglomerular filtration rate; GMgranulocyte macrophage; GM-CSFgranulocyte macrophagecolony-stimulating factor; Hgbhemoglobin; HIVhuman immunodeficiency
virus; IMintramuscular; IVintravenous; LAKlymphokine-activated killer; NKnatural killer; NSnormal saline; PAP-GM-CSFprostatic acid phosphatase granulocyte macrophagecolony-stimulating factor; rHuKGFrecombinant human keratinocyte growth factor; SCsubcutaneous; SDF1-stromal cellderived factor 1-alpha; TNFtumor necrosis factor

Chapter 4. Principles of Biotherapy

Indications

68

Table 10. Characteristics of Targeted Therapies


Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Immunotoxin

Directs cytotoxic action of diphtheria toxin to


cells that express the IL-2
receptor, resulting in inhibition
of cellular protein synthesis
leading to cell
death

Denileukin diftitox
(Ontak)

IV

Treatment of patients
with persistent or recurrent cutaneous Tcell lymphoma whose
malignant cells express the CD25 component of the IL-2 receptor

Hypersensitivity, vascular leak syndrome, hypotension, edema, hypoalbuminemia, fever, chills,


headache, rash, anorexia, reduced lymphocytes,
increased transaminases,
asthenia, infection, pain,
nausea, vomiting, dyspnea, cough, loss of visual acuity

Confirm that patients malignant cells express CD25 prior to


use of agent.
Discontinue use of agent if patients serum albumin is < 3 g/
dl because of risk of capillary leak syndrome.
Premedicate with acetaminophen and an antihistamine.
Incidence of adverse effects diminishes after first two treatment courses.
Store at or below 10C (14F).
Thaw vials in refrigerator for < 24 hours or at room temperature for 12 hours. Agent cannot be refrozen after thawing and must be brought to room temperature before preparing dose.
Concentration of agent must be 15 mcg/ml during all
steps of product preparation.
Vials should not be heated.
Avoid vigorous agitation.
Use prepared solution within 6 hours.
Do not infuse through a filter.
Protect from light.
(Eisai Inc., 2010)

Miscellaneous
biologic
response
modifiers

Exact antineoplastic mechanism is unclear


but may be related to immunomodulatory, antiangiogenic, or
antineoplastic
properties.

Lenalidomide (Revlimid)

PO

Treatment of patients
with transfusion-dependent anemia secondary to low- or intermediate-risk MDS associated with the 5q
chromosomal deletion
In combination with
dexamethasone in patients with multiple myeloma who have received at least one prior therapy

Risk of fetal harm, neutropenia, thrombocytopenia, deep vein thrombosis, pulmonary embolism, pruritus, rash, dry
skin, diarrhea, constipation, nausea, nasopharyngitis, cough, dyspnea,
pharyngitis, fatigue, pyrexia, peripheral edema, asthenia, arthralgia, dizziness, headache, muscle
cramps, upper respiratory
tract infections

Women should avoid becoming pregnant during treatment


and within 4 weeks of discontinuing treatment because of
risk of fetal harm. A pregnancy test should be performed
prior to initiating therapy and repeated every 4 weeks in
women of child-bearing age or with regular menses, and
every 2 weeks in women with irregular menses.
Discontinue lenalidomide immediately if pregnancy occurs
during treatment.
Male patients must adhere to strict methods of contraception and be informed of the teratogenic risks of lenalidomide.
Revlimid is only available under the RevAssist program to
ensure patients are properly informed of fetal risks.
Concomitant use with dexamethasone increases the risk of
developing thrombosis; prophylactic anticoagulation may
be warranted.
Capsules should be taken with water.
Capsules should be swallowed whole and not chewed,
crushed, or broken.
Dosage adjustments are recommended in patients with a
creatinine clearance < 60 ml/min.
(Celgene Corp., 2011)
(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 10. Characteristics of Targeted Therapies (Continued)


Classification
Miscellaneous
biologic
response
modifiers
(cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Pomalidomide
(Pomalyst)

PO

Treatment of patients
with multiple myeloma who have received
at least two prior therapies, including lenalidomide and bortezomib, and have evidence of disease progression within 60
days of completion of
the last therapy

Risk of fetal harm, venous


thromboembolism, neutropenia, anemia, dizziness, confusion, neuropathy, second malignancies,
fatigue, asthenia, peripheral edema, constipation,
diarrhea, nausea, vomiting, pneumonia, upper respiratory tract infections,
back pain

Women should avoid becoming pregnant during treatment


and within 4 weeks of discontinuing treatment because of
risk of fetal harm. A pregnancy test should be performed
prior to initiating therapy and repeated every 4 weeks in
women of child-bearing age or with regular menses, and
every 2 weeks in women with irregular menses.
Male patients must adhere to strict methods of contraception and be informed of the teratogenic risks of pomalidomide.
Discontinue pomalidomide immediately if pregnancy occurs
during treatment.
Pomalyst is only available under the Pomalyst REMS
program to ensure patients are properly informed of fetal risks.
Dose adjustments are recommended for patients with neutropenia or thrombocytopenia.
(Celgene Corp., 2013)

Exact antineoplastic mechanism is unclear


but may be related to immunomodulatory, antiangiogenic, and
anti-inflammatory properties.

Thalidomide (Thalomid)

PO

In combination with
dexamethasone for
treatment in patients
with newly diagnosed
multiple myeloma
Treatment of erythema
nodosum leprosum

Deep vein thrombosis, pulmonary embolism, drowsiness, somnolence, peripheral neuropathy, dizziness,
orthostatic hypotension,
neutropenia, confusion,
anxiety, tremor, insomnia,
depression, fatigue, fever,
anemia, thrombocytopenia, constipation, anorexia, nausea, edema, bone
pain, dyspnea, rash, dry
skin, increased hepatic
enzymes, increased SCr,
muscle weakness

Women should avoid becoming pregnant beginning 4


weeks before treatment, during treatment, and within 4
weeks of discontinuing treatment because of risk of fetal harm.
A pregnancy test should be performed prior to initiating
therapy and repeated every 4 weeks in women of childbearing age or with regular menses, and every 2 weeks in
women with irregular menses.
Thalomid must be dispensed and administered in compliance with the Thalomid REMSTM program.
Male patients must adhere to strict methods of contraception and be informed of the teratogenic risks of thalidomide.
Discontinue thalidomide immediately if pregnancy occurs
during treatment.
Concomitant use with dexamethasone increases the risk of
developing thrombosis; prophylactic anticoagulation may
be warranted.
Because of the potential for significant drowsiness, instruct
patients to avoid situations where impaired mental and/
or physical functioning could put themselves or others at
risk of harm.
(Celgene Corp., 2012)

69

(Continued on next page)

Chapter 4. Principles of Biotherapy

Exact antineoplastic mechanism is unclear


but may be related to immunomodulatory, antiangiogenic, and
anti-inflammatory properties.

70

Table 10. Characteristics of Targeted Therapies (Continued)

Monoclonal
antibodies

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Binds to and inhibits the activity


of human VEGF
to its receptors
(FLT and KDR),
blocking proliferation and formation of new blood
vessels

Bevacizumab
(anti-VEGF
antibody,
Avastin)

IV

In combination with
5-fluorouracilcontaining regimens as firstor second-line treatment for patients with
metastatic carcinoma
of the colon or rectum
In combination with carboplatin and paclitaxel
for first-line treatment
of patients with unresectable, locally advanced, recurrent, or
metastatic nonsquamous NSCLC
Treatment of glioblastoma in patients with
progressive disease
following previous
therapy
In combination with IFN
alfa for treatment of
metastatic renal cell
carcinoma

Hemorrhage, hypertension,
proteinuria, CHF, asthenia, diarrhea, abdominal
pain, headache, neutropenia, hyponatremia, proteinuria, arterial thromboembolic events, GI perforation, wound healing complications, fistula formation
in the GI tract, and/or intra-abdominal abscesses,
infusion reactions

Avoid use for at least 28 days after major surgery; surgical


incision should be fully healed.
Suspend treatment with bevacizumab at least 28 days before elective surgery.
Store agent in refrigerator. Diluted solution may be stored
for up to 8 hours under refrigeration.
Do not freeze.
Do not shake.
Protect from light.
Do not mix or administer with dextrose-containing solutions.
Monitor blood pressure during treatment.
Permanently discontinue medication if patients develop GI
perforation, wound dehiscence requiring medical intervention, serious bleeding, nephrotic syndrome, or hypertensive crisis.
Temporarily suspend if evidence of moderate to severe proteinuria or severe hypertension until evaluation and treatment are provided.
Risk of CHF exists in patients who have previously received
anthracyclines.
(Genentech, Inc., 2011a)

Drug-antibody
conjugate; binds
to CD30+ cells
allowing for internalization of
the antibody
complex and release of MMEA
component that
binds to tubulin
and causes disruption of cell division leading to
apoptosis

Brentuximab vedotin (antiCD30 antibody, Adcetris)

IV

Treatment of Hodgkin
lymphoma in patients
after failure of autologous stem cell transplantation or after failure of 2 multiagent
chemotherapy regimens in patients who
are not candidates for
autologous stem cell
transplantation
Treatment of systemic anaplastic large cell
lymphoma after failure
of 1 multiagent chemotherapy regimen

Peripheral neuropathy, neutropenia, anaphylaxis, infusion reactions, JCV infection resulting in progressive multifocal leukoencephalopathy, StevensJohnson syndrome, fatigue, upper respiratory
tract infection, nausea, diarrhea, vomiting, anemia,
pyrexia, thrombocytopenia, rash, abdominal pain,
cough

Reconstitute vials with 10.5 ml of sterile water. Do not


shake.
Dilute reconstituted solution immediately to a concentration of between 0.41.8 mg/ml and infuse immediately or
store in refrigerator and use within 24 hours.
Concomitant use with bleomycin is contraindicated because of risk of pulmonary toxicity.
Patients can be premedicated with acetaminophen, a histamine antagonist, and a corticosteroid.
Coadministration with CYP3A4 inhibitors, including grapefruit juice, or inducers may increase or decrease concentrations of MMEA component.
(Seattle Genetics, 2012)

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 10. Characteristics of Targeted Therapies (Continued)


Classification
Monoclonal
antibodies
(cont.)

Mechanism
of Action
Binds to extracellular domain
of EGFR, resulting in inhibition
of cell growth
and induction of
apoptosis, and
decreased matrix metalloproteinase and
VEGF production

Drug
Cetuximab
(antiEGFR
antibody,
Erbitux)

Route of
Administration
IV

Side Effects

In patients with EGFRexpressing metastatic


colorectal cancer after
failure of irinotecanand oxaliplatin-based
regimens
With irinotecan or in patients with metastatic
colorectal cancer who
are intolerant of irinotecan
In combination with radiation therapy to treat
local or regionally advanced squamous cell
carcinoma of the head
and neck
In recurrent or metastatic squamous cell carcinoma of the head
and neck progressing
after platinum-based
therapy
In combination with platinum-based therapy
with 5-fluorouracil for
first-line treatment of
patients with recurrent
locoregional or metastatic squamous cell
carcinoma of the head
and neck

Infusion-related reactions
including bronchospasm,
fever, chills, rigors, angioedema, urticaria, hypotension, and stridor; pulmonary toxicity, acneform
rash, dry skin and fissuring, malaise, asthenia, fever, diarrhea, fatigue, nausea, vomiting, anorexia,
leukopenia, hypomagnesemia, weight loss, pharyngitis, cardiopulmonary
arrest

Nursing Considerations
Serious, potentially fatal infusion reactions may occur.
Cardiopulmonary arrest has occurred in patients when
used in combination with radiation therapy.
Dose modification is recommended following development
of acneform rash.
Instruct patients to wear sunscreen and hats and limit sun
exposure.
Premedicate with an H1 antagonist.
Administer through 0.22-micron in-line filter.
Flush line with NS after infusion.
Store agent in refrigerator.
Do not dilute.
Do not shake.
Do not freeze.
Protect from light.
Discard unused portion after 8 hours at room temperature
or 12 hours under refrigeration.
(Eli Lilly & Co., 2012)

Chapter 4. Principles of Biotherapy

Indications

71

(Continued on next page)

72

Table 10. Characteristics of Targeted Therapies (Continued)

Monoclonal
antibodies
(cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Binds to the
transmembrane
protein RANKL
that inhibits osteoclast activity and bone resorption

Denosumab (antiRANKL
antibody,
Prolia,
Xgeva)

SC

Prevention of skeletal
events due to bone
metastases of solid tumors
Treatment to increase
bone mass in men
with nonmetastatic prostate cancer receiving androgen deprivation therapy, and
women with breast
cancer receiving adjuvant aromatase inhibitor therapy at high risk
for bone fractures

Hypocalcemia, osteonecrosis of jaw, fatigue, asthenia, hypophosphatemia,


nausea

Store in refrigerator. Allow 1530 min to warm to room temperature before administration. A 27-gauge needle should
be used to withdraw entire contents from vial for dosing.
Correct and monitor serum calcium, vitamin D, and magnesium before and during treatment.
An oral examination and preventive dentistry should be
performed prior to starting treatment and during therapy.
Good oral hygiene should be practiced during therapy. Invasive dental procedures should be avoided while taking
denosumab.
(Amgen, Inc., 2012b)

Binds to the
complement protein C5, which
inhibits its cleavage to C5a and
C5b; this inhibits
formation of the
terminal components C5b-9,
thus mediating
intravascular hemolysis.

Eculizumab (anti-C5
antibody,
Soliris)

IV

Treatment to reduce hemolysis in patients


with paroxysmal nocturnal hemoglobinuria
Treatment of patients
with atypical hemolytic
uremic syndrome

Headache, nasopharyngitis, back pain, nausea; increased risk of meningococcal infections

Store in refrigerator.
Do not freeze.
Protect from light.
Do not shake.
Do not administer as an IV push or bolus.
Dilute to a final concentration of 5 mg/ml prior to administration.
Allow product to warm to room temperature prior to administration.
Diluted solutions are stable for 24 hours.
Administer by IV infusion over 35 min.
Do not use in patients with unresolved serious Neisseria
meningitides infection or those who are not currently vaccinated against Neisseria meningitides. Vaccinate patients at least 2 weeks prior to the first dose of eculizumab. Revaccinate according to medical guidelines for vaccine use.
Because of the risk of meningococcal infections, eculizumab is only available through a restricted program requiring
enrollment of prescribers and counseling of patients.
(Alexion Pharmaceuticals, Inc., 2011)

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 10. Characteristics of Targeted Therapies (Continued)


Classification
Monoclonal
antibodies
(cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Ibritumomab
tiuxetan
(anti-CD20
antibody,
Zevalin)

IV

Treatment of relapsed or
refractory low-grade,
follicular, or transformed B-cell NHL

Severe and potentially lifethreatening allergic reactions during infusion; fever, chills, rigors, headache, nausea, bronchospasm, dyspnea, myalgia,
arthralgia, asthenia, prolonged B-cell lymphocytopenia, leukopenia, thrombocytopenia, neutropenia,
anemia, severe cutaneous
and mucocutaneous reactions, secondary leukemia
or MDS

Drug is combined with rituximab.


Premedicate with acetaminophen and diphenhydramine.
Patients with a platelet count < 100,000/mm3 should not be
treated with ibritumomab.
Administer ibritumomab through a 0.22 micron in-line filter.
Administered dose cannot exceed 32 mCi regardless of patients weight.
Drug is not transported with radioisotope; radiolabeling must
be done by appropriate personnel in a specialized facility.
Drug is intended as single-course treatment.
Monitor closely for extravasation.
Store in refrigerator.
Do not freeze.
Use of antiplatelet or anticoagulant drugs should be avoided following recent use of ibritumomab.
(Spectrum Pharmaceuticals, Inc., 2011)

Binds CTLA-4
and blocks its
negative regulation of T-cell activation and proliferation, increasing T-cell antitumor immune response

Ipilimumab
(anti-CTLA-4
antibody,
Yervoy)

IV

Treatment of unresectable or metastatic melanoma

Immune-mediated adverse
reactions resulting in enterocolitis, hepatitis, dermatitis, neuropathy, or endocrinopathy

Store in refrigerator.
Do not shake.
Diluted product may be stored at room temperature or under refrigeration for up to 24 hours.
Protect from light.
Prior to each dose, evaluate patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and perform laboratory assessment of blood
chemistries, liver function, and thyroid function.
(Bristol-Myers Squibb Co., 2012)

Binds to CD20
on B cells and
B-cell CLL resulting in ADCC
and complement-dependent
cytotoxicity

Ofatumumab
(anti-CD20
antibody,
Arzerra)

IV

Treatment of CLL in patients refractory to


fludarabine and alemtuzumab

Infusion reactions including


bronchospasm, dyspnea,
laryngeal edema, pulmonary edema, flushing, hypertension, hypotension,
syncope, myocardial infarction, back or abdominal pain, fever, rash, urticaria, or angioedema; severe neutropenia or thrombocytopenia, progressive
multifocal leukoencephalopathy, hepatitis B infection/reactivation, intestinal
obstruction, infections

Do not shake.
Do not freeze.
Protect from light.
Administer through in-line filter.
Premedicate with acetaminophen, H1 antagonist, and a
corticosteroid.
Prepare doses in NS.
Store diluted solution under refrigeration.
Infusion should be started within 12 hours of preparation
and discarded after 24 hours.
(GlaxoSmithKline, 2011a)

73

(Continued on next page)

Chapter 4. Principles of Biotherapy

Binds to CD20
on B cells resulting in direct delivery of the radioactive isotope
indium-111 or yttrium-90 that induces cell damage through the
formation of free
radicals

74

Table 10. Characteristics of Targeted Therapies (Continued)

Monoclonal
antibodies
(cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Binds to EGFR
and competitively inhibits binding of ligands to
this receptor; this
prevents receptor
autophosphorylation and activation of receptorassociated kinases that results in
inhibition of cell
growth, induction
of apoptosis, decreased production of proinflammatory cytokines
and VGFs, and
internalization of
EGFR

Panitumumab
(antiEGFR
antibody,
Vectibix)

IV

Single-agent treatment
for EGFR-expressing metastatic colorectal carcinoma with disease progression on
or following fluoropyrimidine-, oxaliplatin-,
or irinotecan-containing regimens

Dermatologic toxicity including dermatitis acneform,


pruritus, erythema, rash,
skin exfoliation, paronychia, dry skin, and skin fissures, which may be complicated by abscesses and
sepsis; fatigue, abdominal
pain, hypomagnesemia,
infusion reactions, keratitis

Advise patients to wear sunscreen and a hat to limit sun


exposure.
Dose modification is recommended following infusion-related reactions or dermatologic toxicity.
Drug must be given by IV infusion pump via a 0.22 micron
in-line filter.
Dilute dose with NS.
Do not shake diluted product.
Do not exceed a final concentration of 10 mg/ml.
Store in refrigerator.
Do not freeze.
Protect from light.
Use diluted solution within 6 hours at room temperature or
within 24 hours if under refrigeration.
Combination of panitumumab with oxaliplatin-containing
regimens is contraindicated in patients with mutant KRAS
metastatic colorectal cancer or in whom KRAS status is
unknown.
(Amgen, Inc., 2012a)

Targets the extracellular dimerization domain


of HER2 protein
that blocks
ligand-dependent
heterodimerization of HER2 with
other similar proteins. This inhibits
intracellular signaling that results
in slowing cell
growth and triggering apoptosis.
Also triggers antibody-dependent
cell-mediated cytotoxicity.

Pertuzumab
(Perjeta)

IV

In combination with
trastuzumab and
docetaxel for treatment of patients with
HER2+ metastatic
breast cancer

Left ventricular dysfunction,


infusion-related reactions,
fatigue, asthenia, peripheral edema, mucosal inflammation, alopecia, rash,
nail changes, diarrhea,
nausea, vomiting, neutropenia, anemia, peripheral neuropathy, headache,
myalgia, anorexia

Monitor LVEF during treatments and hold doses if ejection


fraction decreases to < 40% or 10% from baseline levels to between 40%45%.
Do not administer mixed with other IV medications.
Store in refrigerator. Keep vials in original container until
time of use to protect from light.
Dilute in 250 ml 0.9% saline only and mix with gentle inversion. Do not shake.
If not used immediately, diluted solutions can be stored under refrigeration for up to 24 hours.
May cause fetal harm when administered to pregnant women. Determine pregnancy status of patients prior to starting treatment with pertuzumab.
Patients must be tested for HER2 status before initiation of
treatment because use has only been studied in patients
who overexpress HER2 protein.
(Genentech, Inc., 2012b)

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 10. Characteristics of Targeted Therapies (Continued)


Classification
Monoclonal
antibodies
(cont.)

Mechanism
of Action
Binds to CD20
on B cells resulting in activation
of complementdependent cytotoxicity as well
as ADCC

Drug
Rituximab
(anti-CD20
antibody,
Rituxan)

Route of
Administration
IV

Side Effects

Nursing Considerations

Treatment of relapsed
or refractory low-grade
follicular CD20+ B-cell
NHL
First-line treatment of
follicular CD20+ B-cell
NHL in combination
with chemotherapy
and as monotherapy in
patients who have had
a complete or partial
response to rituximab
plus chemotherapy
Treatment of low-grade
CD20+ B-cell NHL in
patients with stable
disease or who have
achieved a partial or
complete response with
CVP chemotherapy
First-line treatment of diffuse large B-cell CD20+
NHL in combination
with CHOP or other anthracycline-based chemotherapy regimen
First-line treatment
in combination with
fludarabine and cyclophosphamide in patients with CD20+ CLL
In combination with methotrexate to treat moderate to severe rheumatoid arthritis in patients
who have not responded to one or more TNFantagonist therapies
In combination with glucocorticoids in patients with Wegener
granulomatosis or microscopic polyangiitis

Severe infusion-related reactions including urticaria, hypotension, angioedema, hypoxia, or bronchospasm; fever, chills, rigors,
headache, dyspnea, myalgia, arthralgia, prolonged
B-cell lymphopenia, leukopenia, infection, asthenia, nausea, rash, hepatitis B reactivation, progressive multifocal leukoencephalopathy, cardiac arrhythmias, bowel obstruction and/or perforation, renal toxicity

Administer only by IV infusion.


Store in refrigerator.
Do not freeze.
Do not shake product.
Protect vials from direct sunlight.
Agent is stable for 24 hours under refrigeration.
Consider premedication with acetaminophen and diphenhydramine.
Infusion-related side effects may resolve with slowing or
suspending infusion.
Incidence of infusion-related side effects is reduced with
subsequent infusions.
Potential exists for development of TLS within 1224 hours
after infusion.
Prophylaxis against Pneumocystis jiroveci pneumonia and
herpesvirus infections in patients with CLL for up to 12
months after treatment.
(Genentech, Inc., 2012c)

Chapter 4. Principles of Biotherapy

Indications

75

(Continued on next page)

76

Table 10. Characteristics of Targeted Therapies (Continued)

Monoclonal
antibodies
(cont.)

Mechanism
of Action
Binds to CD20
on pre-B and
mature lymphocytes and B-cell
NHL resulting in
apoptosis, complement-dependent cytotoxicity, and ADCC;
ionizing radiation caused by
iodine-131 (131I)
results in additional cell death.

Drug
Tositumomab 131I
(anti-CD20
antibody,
Bexxar)

Route of
Administration
IV

Indications

Side Effects

Nursing Considerations

Treatment of patients
with CD20+ relapsed
or refractory, lowgrade, follicular, or
transformed NHL including patients refractory to rituximab

Anaphylaxis, hypothyroidism, severe and prolonged


thrombocytopenia, anemia, neutropenia, allergic reactions, asthenia, fever, infection, chills, rigors,
sweating, nausea, vomiting, hypotension, dyspnea,
bronchospasm, abdominal
pain, rash, secondary leukemia/MDS or nonhematologic malignancies

Agent is not indicated for initial treatment of CD20+ NHL.


Agent should not be administered to patients with platelet
count < 100,000/mm3 or neutrophil count < 1,500/mm3.
Treatment involves two separate steps (dosimetric dose
and therapeutic dose) separated by 714 days.
Thyroid-blocking agents should be given beginning 24
hours prior to tositumomab 131I therapy and continued for
at least 14 days.
Premedicate with acetaminophen and diphenhydramine.
The same IV tubing set must be used throughout the entire
dosimetric or therapeutic steps to prevent loss of drug.
Administer both doses through a 0.22 micron in-line filter.
Instruct patients on how to minimize exposure of other people to radioactivity that will remain in their system for several days.
Only personnel trained in handling radioactive agents
should prepare and administer this agent.
Store in refrigerator.
Do not freeze.
Protect from light.
Do not shake.
(GlaxoSmithKline, 2012a)

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 10. Characteristics of Targeted Therapies (Continued)


Classification
Monoclonal
antibodies
(cont.)

Mechanism
of Action
Binds to the extracellular domain of HER2,
resulting in mediation of ADCC
against cells that
overproduce
HER2

Drug
Trastuzumab (antiHER2 antibody, Herceptin)

Route of
Administration
IV

Side Effects

Nursing Considerations

In combination with
treatment regimens
of doxorubicin, cyclophosphamide, and paclitaxel or docetaxel and carboplatin or
as monotherapy after
anthracycline-based
regimens for adjuvant treatment of patients with HER2-overexpressing node-positive or node-negative
breast cancer
As single-agent therapy for treatment of patients with metastatic
breast cancer whose
tumors overexpress
HER2 and who have
received one or more
chemotherapy regimens for their disease,
or in combination with
paclitaxel for treatment
of patients with metastatic breast cancer
whose tumors overexpress HER2 and who
have not previously received chemotherapy
for their disease
As first-line therapy in
combination with cisplatin and capecitabine
or 5-fluorouracil for
treatment of HER2overexpressing metastatic gastric cancer
or gastroesophageal junction adenocarcinoma

Infusion reactions of chills,


fever, headache, dizziness, dyspnea, hypotension, rash, and asthenia;
pulmonary toxicity related
to infusion; cardiomyopathy, hypersensitivity reactions, diarrhea, leukopenia, anemia, neutropenia,
infection, thrombosis

Administer only by IV infusion.


Store in refrigerator.
Do not freeze.
Solution reconstituted with bacteriostatic water is stable for
28 days under refrigeration.
Solution reconstituted with sterile water must be used immediately and not saved.
Dilute dose only with NS. Do not use D5W.
Do not shake product.
HER2 protein overexpression is seen in 25%30% of primary breast cancers.
Do not administer concurrently with doxorubicin and cyclophosphamide; intended to be administered following completion of doxorubicin and cyclophosphamide.
LVEF must be determined prior to initiation and during
treatment. Cardiomyopathy is increased in patients also
receiving an anthracycline-containing regimen.
(Genentech, Inc., 2010)

Chapter 4. Principles of Biotherapy

Indications

77

(Continued on next page)

78

Table 10. Characteristics of Targeted Therapies (Continued)


Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Monoclonal
antibodies
(cont.)

Binds to the extracellular domain of HER2,


resulting in receptor-mediated
internalization
and intracellular
release of emtansine (DM1),
which disrupts
the cells microtubule network,
leading to cell
cycle arrest and
apoptosis

Ado-trastuzumab emtansine
(anti-HER2
antibody
conjugated
with emtansine,
Kadcyla)

IV

Treatment of patients
with HER2+ metastatic breast cancer who
have previously been
treated with trastuzumab and a taxane
either alone or in combination

Hepatotoxicity, cardiotoxicity, thrombocytopenia, pulmonary toxicity, peripheral


neuropathy, infusionrelated reactions, hypersensitivity, diarrhea, constipation, nausea, fatigue,
musculoskeletal pain, epistaxis

First infusion is administered over 90 min. Patients should


be monitored for infusion-related reactions during and for
at least 90 min following completion of the infusion. If infusion is tolerated, subsequent infusions can be infused
over 30 min with monitoring continuing for at least an additional 30 min.
Dose reductions based on the manufacturers recommendations should occur in the event of certain adverse effects.
Ado-trastuzumab emtansine should be infused using a 0.22
micron inline nonprotein-absorptive polyethersulfone filter.
Do not mix or infuse ado-trastuzumab emtansine with other medications.
Caution should be made not to confuse ado-trastuzumab
emtansine with trastuzumab (Herceptin).
Ado-trastuzumab emtansine should only be diluted with
0.9% saline solution. Do not dilute with D5W.
Prepared diluted solutions can be stored under refrigeration for up to 4 hours.
Do not freeze or shake prepared solutions.
Ado-trastuzumab emtansine can cause fetal harm when
administered to pregnant women. Determine pregnancy
status of patients prior to initiating ado-trastuzumab emtansine and inform patients of fetal risks and the need for
effective contraception during treatment with ado-trastuzumab emtansine.
Concomitant use with CYP3A4 inhibitors should be avoided
because of the risk of increased toxicity. If use of CYP3A4
inhibitors cannot be avoided, use of ado-trastuzumab emtansine may be delayed until the CYP3A4 inhibitor has
cleared from the patients system or if the patient is monitored closely for adverse effects.
(Genentech, Inc., 2013)

Small
molecule
inhibitors

Inhibits VEGF
receptors with
tyrosine kinase
activity that interferes with tumor angiogenesis, growth, and
progression

Axitinib
(Inlyta)

PO

Treatment of advanced
renal cell carcinoma
after failure of previous
therapy

Hypertension, thromboembolism, hemorrhage, GI


perforation, GI fistula formation, hypothyroidism,
PRES, proteinuria, elevated LFTs

Administer doses every 12 hours.


May be taken with or without food.
Concomitant use with CYP3A4/5 inhibitors, including
grapefruit juice, or inducers may alter exposure to axitinib
and should be avoided. If concomitant use cannot be
avoided, dose adjustment of axitinib should be made.
Dosing should be held beginning at least 24 hours before
surgery because of risk of impaired wound healing. Time
to restart therapy is based on clinical judgment.
(Pfizer Inc., 2012b)
(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 10. Characteristics of Targeted Therapies (Continued)


Classification
Small
molecule
inhibitors
(cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Bortezomib (Velcade)

IV, SC

Treatment of patients
with multiple myeloma or mantle cell lymphoma who have received at least one prior therapy

Peripheral neuropathy, hypotension, cardiomyopathy, pulmonary infiltrates,


nausea, vomiting, diarrhea, constipation, blurred
vision, fatigue, myelosuppression, PRES, hyperbilirubinemia, hepatitis

Use with caution in patients with severe renal or hepatic


disease.
Monitor hydration status and treat as necessary.
Platelet count should be > 70,000/mm3 and neutrophil
count > 1,000/mm3 when bortezomib is combined with
melphalan and prednisone.
Reconstitute only with NS.
Use reconstituted solutions within 8 hours.
Concentrations of SC (2.5 mg/ml) or IV (1 mg/ml) doses are different, and final volume depends on calculated dose.
SC injection site should be rotated in thigh or abdomen. Select new site at least 1 inch from old site, and avoid tender or bruised areas.
Concomitant use with CYP3A4 inhibitors, including grapefruit juice, or inducers may alter exposure to bortezomib.
Do not use in pediatric patients.
Fatal if given intrathecally.
(Millennium Pharmaceuticals, Inc., 2012)

Inhibits BCRABL tyrosine kinase created by


the Ph+ genetic
abnormality, inhibiting proliferation, and induces apoptosis in
BCR-ABL+ cell
lines

Bosutinib
(Bosulif)

PO

Treatment of adult patients with chronic, accelerated, or blast


phase Ph+ CML that is
resistant or intolerant
to other therapies

Diarrhea, nausea, vomiting,


abdominal pain, thrombocytopenia, anemia, neutropenia, hepatic toxicity,
fluid retention resulting in
pericardial effusion, pleural effusion, pulmonary or
peripheral edema, fever,
rash, headache

Take with food.


Monitor liver transaminases and hold dose if elevations > 5
ULN occur. Discontinue if bilirubin elevations > 2 ULN
or alkaline phosphatase elevations occur.
Hold dosing and adjust dose if severe or persistent thrombocytopenia or neutropenia occur. Hold dosing if other
clinically significant moderate or severe nonhematologic
or toxicities occur, then restart once symptoms abate.
Concomitant use with CYP3A4 inhibitors, including grapefruit juice, or inducers may alter exposure to bosutinib.
Concomitant use with P-glycoprotein inhibitors such as
verapamil or diltiazem may alter exposure to bosutinib.
Avoid use in pregnant women because of risk of fetal harm.
Use of proton pump inhibitors may reduce bosutinib concentration and is not recommended. Use of antacids or H2
blockers should be separated from bosutinib administration by 2 hours.
(Pfizer Inc., 2012a)

79

(Continued on next page)

Chapter 4. Principles of Biotherapy

Inhibits chymotrypsin-like activity of 26S proteasome resulting in disruption


of cellular homeostatic mechanisms that
can lead to cell
death

80

Table 10. Characteristics of Targeted Therapies (Continued)

Small
molecule
inhibitors
(cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Inhibits tyrosine
kinase activity of
multiple receptor
kinases involved
with oncogenesis, metastasis,
tumor angiogenesis, and maintenance of the
tumor microenvironment

Cabozantinib
(Cometriq)

PO

Treatment of patients
with progressive, metastatic, medullary thyroid cancer

GI perforations and fistulas, hemorrhage, thromboembolism, wound complications, hypertension, osteonecrosis of the jaw, palmar-plantar erythrodysesthesia, proteinuria, PRES,
diarrhea, stomatitis, nausea, oral pain, constipation, abdominal pain, vomiting, fatigue, weight loss,
loss of appetite, dysgeusia, hypocalcemia, hypophosphatemia, hepatotoxicity, lymphopenia, neutropenia, thrombocytopenia

Do not administer with food. Patients should not eat at least


2 hours before and 1 hour after taking cabozantinib.
Capsules should be swallowed whole and not opened.
Missed doses should not be taken within 12 hours of the
next dose.
Concomitant use with CYP3A4 inhibitors, including grapefruit juice, or inducers may alter exposure to cabozantinib.
Dose should be adjusted or discontinued permanently in
the event of certain adverse effects. See manufacturers
prescribing information for full details.
Treatment with cabozantinib should be held at least 28
days prior to elective surgery and resumed based on clinical assessment of wound healing.
(Exelixis, Inc., 2012)

Binds to and inhibits the 20S


proteasome, resulting in anti
proliferative and
antiapoptotic activities

Carfilzomib
(Kyprolis)

IV

Treatment of patients
with multiple myeloma who have received
at least two previous
therapies and whose
disease has progressed on or within 60 days of the last
treatment

Cardiac arrest, CHF, myocardial ischemia, pulmonary hypertension, dyspnea, infusion reactions
including fever, chills, arthralgia, myalgia, flushing,
hypotension, syncope, or
angina, TLS, thrombocytopenia, anemia, leukopenia, hepatic toxicity, renal
toxicity, fatigue, diarrhea,
headache, peripheral edema, back pain, peripheral neuropathy, herpesvirus
infection

Administer over 210 min on two consecutive days.


Premedicate with dexamethasone 4 mg PO/IV prior to each
dose during the first cycle and in subsequent cycles if infusion reactions occur.
Hold and modify dose if patients develop hematologic, cardiac, renal, or hepatic toxicities, pulmonary hypertension,
pulmonary complications, peripheral neuropathy, or other
grade 34 toxicities.
Do not administer mixed with other IV medications. Infusion
line should be flushed with NS or D5W before and after
administration of carfilzomib.
Store unopened vials in refrigerator. Reconstituted product is stable for 24 hours under refrigeration or 4 hours at
room temperature.
Antiviral prophylaxis should be considered in patients with
a history of herpes zoster infection.
Because of the risk of fatigue, dizziness, fainting, or hypotension, advise patients not to drive or operate heavy machinery if they experience these symptoms.
(Onyx Pharmaceuticals, Inc., 2012)

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 10. Characteristics of Targeted Therapies (Continued)


Classification
Small
molecule
inhibitors
(cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Crizotinib
(Xalkori)

PO

Treatment of locally advanced or metastatic


ALK+ NSCLC

Hepatotoxicity, pneumonitis, QT prolongation, vision changes, nausea, diarrhea, vomiting, edema,


constipation, neutropenia,
fatigue, anorexia, dizziness, dyspnea

Determination of ALK+ NSCLC is required for treatment.


May be taken with or without food.
Capsules should be swallowed whole and not crushed,
chewed, or opened.
Monitor and correct for hypomagnesemia and hypokalemia to
reduce risk of QT prolongation. Do not use in patients with
hypokalemia, hypomagnesemia, or long QT syndrome.
Concomitant use with CYP3A4 inhibitors, including grapefruit juice, or inducers may alter exposure to crizotinib.
(Pfizer Inc., 2013)

Inhibits multiple tyrosine kinases, including BCR-ABL,


SRC family, cKIT, EPHA2, and
PDGFR-beta

Dasatinib
(Sprycel)

PO

Treatment of newly diagnosed Ph+ CML


Treatment of chronic, accelerated, or
myeloid or lymphoid
blast-phase CML with
resistance or intolerance to prior therapy
including imatinib
Treatment of Ph+ ALL
with resistance or intolerance to prior therapy

Myelosuppression, fluid retention including pleural


and pericardial effusion,
prolonged QT interval by
ECG, diarrhea, nausea,
abdominal pain, vomiting,
bleeding, cardiomyopathy,
pulmonary arterial hypertension

Do not crush or cut tablets.


Tablets may be taken with or without food and either in the
morning or evening.
Use with caution if patients are taking anticoagulants.
Concomitant use with CYP3A4 inhibitors, including grapefruit juice, or inducers may alter exposure to dasatinib and
should be avoided. If concomitant use cannot be avoided,
dose adjustment of dasatinib should be made.
Use of proton pump inhibitors or H2 antagonists may reduce dasatinib concentration and is not recommended.
Use of antacids should be separated from administration
of dasatinib by 2 hours.
Elevation of transaminases or bilirubin, hypocalcemia, and
hypophosphatemia may occur. Hypocalcemia may require
oral calcium supplements.
(Bristol-Myers Squibb Co., 2011)

Inhibits the intracellular phosphorylation


of tyrosine kinase associated
with EGFR, expressed on the
surfaces of normal and cancer
cells

Erlotinib
(Tarceva)

PO

Treatment of locally advanced or metastatic


NSCLC after failure of
at least one prior chemotherapy regimen
As monotherapy for
maintenance treatment in patients with
locally advanced or
metastatic NSCLC
who have not progressed after 4 cycles of platinum-based
therapy

Rash, diarrhea, anorexia, fatigue, dyspnea, GI bleeding or perforation, conjunctivitis, nephrotoxicity, hepatotoxicity, myocardial infarction, cerebrovascular
accident, ocular disorders,
elevated INR
Rare reports of serious ILD
(acute onset of new or
progressive pulmonary
symptoms [e.g., dyspnea,
cough, fever]); interrupt
therapy for evaluation if
these symptoms develop.

Patients should take on an empty stomach at least 1 hour


before or 2 hours after food.
Concomitant use with CYP3A4 inhibitors or inducers may
alter exposure to erlotinib.
Monitor LFTs and consider dose reductions.
Monitor INR in patients receiving warfarin.
Monitor for GI bleeding and elevated INR.
Diarrhea can be managed with loperamide. Both diarrhea
and skin reactions may require dose reduction or temporary interruption of therapy.
(Genentech, Inc., 2012d)

81

(Continued on next page)

Chapter 4. Principles of Biotherapy

Inhibits multiple
tyrosine kinases,
including ALK,
which reduces
tumor cell proliferation and survival

82

Table 10. Characteristics of Targeted Therapies (Continued)


Mechanism
of Action

Small
molecule
inhibitors
(cont.)

Drug

Route of
Administration

Erlotinib
(Tarceva)
(cont.)

Binds to
FKBP12 intracellular protein and
inhibits mTOR,
which is a serine-threonine
kinase downstream of the
PI3K/AKT pathway, resulting in
reduced cell proliferation and angiogenesis

Everolimus
(Afinitor;
Afinitor
Disperz
tablets for
oral suspension)

Indications

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Side Effects

Nursing Considerations

Noninfectious pneumonitis,
infections, oral ulceration,
renal failure, diarrhea, fatigue, nausea, vomiting,
edema, nasopharyngitis, epistaxis, rash, weight
loss, decreased appetite, dysgeusia, headache,
cough, dyspnea, anemia,
leukopenia, thrombocytopenia, hyperglycemia, hypercholesterolemia, elevated hepatic transaminases, hypertriglyceridemia, hypoalbuminemia,
hypokalemia

Patients should take drug at the same time each day and
consistently either with or without food.
Tablets should be swallowed whole with a full glass of water.
Dose adjustment is required in hepatic insufficiency.
Concomitant use with CYP3A4 inhibitors, including grapefruit juice, or inducers may alter exposure to everolimus.
Concomitant use with P-glycoprotein inhibitors such as
verapamil or diltiazem may alter exposure to everolimus.
Everolimus whole blood trough levels should be monitored
routinely using the same assay and laboratory throughout treatment. Measure trough concentrations 2 weeks after starting treatment and with changes in dose, interacting drugs, hepatic function, or dosage form (oral tablets or
tablets for oral suspension).
Titrate dosage to achieve trough levels of 515 ng/ml.
Prepare oral suspension in 25 ml of water only, immediately
prior to use, and discard if not administered within 60 min.
Prepared doses should not exceed 10 mg. If higher doses are required, prepare a second dose. Once tablets are
added to water, allow 3 min for suspension to form, stir
gently, and have patients drink. After administration, add
25 ml additional water to the same glass and stir with the
same spoon to resuspend any remaining particles and
administer to patient.
Oral suspension may be administered using an oral syringe
in doses not to exceed 10 mg per syringe. After dosing
via an oral syringe, rinse the syringe with 5 ml of water
to capture remaining drug particles and administer to patient.
(Novartis Pharmaceuticals Corp., 2012a)

In combination with
gemcitabine for treatment of locally advanced, unresectable,
or metastatic pancreatic cancer
PO

Treatment of postmenopausal women with


advanced hormone
receptorpositive,
HER2-negative breast
cancer in combination
with exemestane after patients have failed
treatment with letrozole or anastrozole
Treatment of adults with
unresectable, locally advanced or metastatic progressive neuroendocrine tumors of
pancreatic origin
Treatment of adult patients with advanced
renal cell carcinoma after failed treatment with sunitinib or
sorafenib
Treatment of subependymal giant cell astrocytoma in patients
with tuberous sclerosis
complex

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 10. Characteristics of Targeted Therapies (Continued)


Classification
Small
molecule
inhibitors
(cont.)

Mechanism
of Action
Inhibits BCRABL tyrosine kinase created by
the Ph+ genetic
abnormality, inhibiting proliferation and inducing apoptosis in
BCR-ABL+ cell
lines

Drug
Imatinib
mesylate
(Gleevec)

Route of
Administration
PO

Side Effects

Nursing Considerations

Treatment of patients
with newly diagnosed
Ph+ CML in chronic phase
Treatment of patients
with Ph+ CML in
blast crisis, accelerated phase, or chronic phase after failure of
IFN alfa therapy
Treatment of patients
with relapsed or refractory Ph+ ALL
Treatment of patients
with myelodysplastic/
myeloproliferative disorders associated with
PDGFR gene rearrangements
Treatment of patients
with systemic mastocytosis without certain
c-KIT mutations
Treatment of patients
with hypereosinophilic syndrome and/or
chronic eosinophilic
leukemia in the presence of certain mutations
Treatment of patients
with unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans
Treatment of patients
with unresectable and/
or metastatic GIST
Adjuvant treatment of
resected GIST

Edema and fluid retention,


GI irritation, nausea, vomiting, anemia, neutropenia,
thrombocytopenia, hepatotoxicity, cardiomyopathy,
hemorrhage, dermatologic
toxicity, hypothyroidism

Weigh patients frequently, and monitor for signs and symptoms of fluid retention.
Ensure that patients take imatinib with food and a large
glass of water.
For patients who are unable to swallow tablets, the tablets
may be dispersed in a glass of water or apple juice immediately before administration.
Monitor CBC, differential, and LFTs.
CYP3A4 inducers may decrease levels of imatinib and
should be avoided or a 50% dose increase should be
considered.
CYP3A4 inhibitors, including grapefruit juice, may increase
exposure to imatinib and should be avoided.
Imatinib may increase activity of warfarin, and concomitant
use should be avoided.
Advise women of childbearing age not to become pregnant
while taking imatinib.
(Novartis Pharmaceuticals Corp., 2012b)

Chapter 4. Principles of Biotherapy

Indications

83

(Continued on next page)

84

Table 10. Characteristics of Targeted Therapies (Continued)

Small
molecule
inhibitors
(cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

4-Anilinoquinazoline kinase inhibitor of the intracellular tyrosine kinase domains of both


EGFR and
HER2 receptors

Lapatinib
(Tykerb)

PO

In combination with
capecitabine for treatment of patients with
advanced or metastatic breast cancer
whose tumors overexpress HER2 and who
have received prior
therapy including an
anthracycline, a taxane, and trastuzumab
In combination with letrozole in postmenopausal women with
hormone receptor
positive breast cancer that overexpresses HER2

Diarrhea, palmar-plantar
erythrodysesthesia, nausea, rash, vomiting, diarrhea, fatigue, decreased
LVEF, hepatotoxicity, pulmonary toxicity, QT prolongation

Instruct patients to take lapatinib at least 1 hour before or 1


hour after a meal. However, capecitabine should be taken
with food or within 30 min after food.
Lapatinib dose should be taken once daily; do not divide
the daily dose.
Modify the dose in patients with severe hepatic impairment.
Concomitant use with CYP3A4 inhibitors, including grapefruit juice, or inducers may alter exposure to lapatinib and
should be avoided or the dose adjusted if concomitant
use is required.
Confirm normal ejection fraction before beginning drug.
Lapatinib should be discontinued in patients if LVEF
drops below lower limits of normal.
Diarrhea may be managed with antidiarrheal agents; replace fluids and electrolytes if severe.
Lapatinib may cause fetal harm when administered to pregnant women.
Monitor and correct for hypomagnesemia and hypokalemia
to reduce risk of QT prolongation.
(GlaxoSmithKline, 2012b)

Binds to and stabilizes the inactive conformation of BCRABL, the kinase


produced by the
Ph chromosome

Nilotinib
(Tasigna)

PO

Treatment of patients
newly diagnosed with
Ph+ CML in chronic
phase
Treatment of chronicand accelerated-phase
Ph+ CML in adult patients resistant or intolerant to prior therapy
including imatinib

Rash, pruritus, nausea, fatigue, headache, constipation, diarrhea, vomiting,


thrombocytopenia, neutropenia, anemia, elevated lipase, hepatotoxicity, electrolyte abnormalities, prolonged QT interval
Sudden deaths have been
reported.

Instruct patients to swallow capsules whole with water. For


patients unable to swallow capsules, the contents may
be mixed in one teaspoon of applesauce and taken within 15 min.
Twice-daily doses should be taken at 12-hour intervals.
No food should be consumed for at least 2 hours before the
dose and 1 hour after.
Check CBC every 2 weeks for the first 2 months, then
monthly.
Monitor and correct for hypomagnesemia and hypokalemia to
reduce risk of QT prolongation. Do not use in patients with
hypokalemia, hypomagnesemia, or long QT syndrome.
Obtain ECG at baseline, 7 days after initiation, and periodically to monitor QTc.
Avoid concomitant use of drugs known to prolong QT interval.
Concomitant use of CYP3A4 inhibitors, such as grapefruit juice, or inducers may alter exposure to nilotinib and
should be avoided. Dose reduction may be necessary if
inhibitors must be given, and the QTc should be monitored closely.
(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 10. Characteristics of Targeted Therapies (Continued)


Classification

Mechanism
of Action

Small
molecule
inhibitors
(cont.)

Drug

Route of
Administration

Indications

Side Effects

Nilotinib
(Tasigna)
(cont.)

Inhibits VEGF
receptors with
tyrosine kinase
activity, which interferes with tumor angiogenesis, growth, and
progression

Pazopanib
(Votrient)

Nursing Considerations
Do not use in patients who are pregnant or breast-feeding.
Women of childbearing age should use effective contraception during treatment.
Concomitant use of proton pump inhibitors may reduce absorption of nilotinib.
(Novartis Pharmaceuticals Corp., 2011)

PO

Treatment of advanced
renal cell carcinoma

Hepatotoxicity, LVEF dysfunction, hemorrhage,


thromboembolism, GI perforation, GI fistula formation, PRES, hypertension,
hypothyroidism, proteinuria, infection, diarrhea,
hair color changes, nausea, anorexia, vomiting,
fatigue, leukopenia, neutropenia, thrombocytopenia, lymphocytopenia, hypophosphatemia, hyperglycemia, hypomagnesemia, headache, myalgia

Doses should be taken once daily at least 1 hour before or


2 hours after a meal.
Do not crush tablets.
Concomitant use of CYP3A4 inhibitors, including grapefruit
juice, and inducers may alter exposure to pazopanib and
should be avoided.
Measure LFTs before start of pazopanib use, and monitor
at least monthly during the first 4 months of treatment and
then periodically thereafter.
Discontinue the drug permanently in patients in whom ALT
> 3 ULN and bilirubin levels increase > 2 ULN while
on pazopanib.
Use with caution in patients with a history of QT prolongation or concomitantly using other drugs that prolong QT
interval.
Stop use of drug at least 7 days prior to planned surgery,
and restart based on clinical judgment.
Concomitant use with simvastatin may increase risk of ALT
elevations.
(GlaxoSmithKline, 2012c)

Chapter 4. Principles of Biotherapy


85

(Continued on next page)

86

Table 10. Characteristics of Targeted Therapies (Continued)

Small
molecule
inhibitors
(cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Inhibits multiple membranebound and intracellular kinases


involved in oncogenesis, tumor angiogenesis, and maintenance of tumor
microenvironment

Regorafenib
(Stivarga)

PO

Treatment of patients
with metastatic
colorectal cancer who
have previously been
treated with other therapies including a fluoropyrimidine, oxaliplatin, irinotecan, antiVEGF therapy, and
anti-EGFR therapy (if
KRAS wild type)
Treatment of patients
with locally advanced,
unresectable or metastatic GIST following previous treatment
with imatinib and sunitinib

Hepatotoxicity, hemorrhage,
hand-foot skin reactions,
rash, hypertension, cardiac ischemia, myocardial
infarction, PRES, GI perforation or fistula, complications with wound healing,
asthenia, fatigue, pain, fever, anorexia, diarrhea,
mucositis, weight loss, infection, dysphonia, anemia, thrombocytopenia,
lymphopenia, hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia, proteinuria

Patients should take drug at the same time each day.


Tablets should be swallowed whole with a low-fat breakfast.
Reduce dose for grade 2 hand-foot skin reactions, and hold
dose for grade 2 hand-foot skin reactions that recur or do
not improve within 7 days despite dose reduction.
Hold dose for grade 2 hypertension.
Hold dose for any other grade 34 adverse reaction and
then restart at a reduced dose after patient recovers from
the reaction. Restart dosing following grade 4 reactions
only if the potential benefit outweighs the risks.
Hold dose if elevations in hepatic transaminases, and restart only if the potential for benefit outweighs the risk of
hepatotoxicity. Discontinue dosing if transaminase (AST
or ALT) levels are > 20 ULN or > 3 ULN with a bilirubin > 2 ULN or recurrent elevated transaminases > 5
ULN despite dose reduction.
May cause fetal harm when administered to pregnant women.
Concomitant use with CYP3A4 inhibitors, including grapefruit juice, or inducers may alter exposure to regorafenib.
(Bayer Healthcare, 2013)

Inhibits JAK 1
and 2, which
mediate cytokines and growth
factors responsible for hematopoiesis and immune function

Ruxolitinib
(Jakafi)

PO

Treatment of patients
with intermediate- or
high-risk myelofibrosis,
including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocytopenia myelofibrosis

Thrombocytopenia, anemia,
neutropenia, infections

Store at room temperature.


May be taken with or without food.
If patients are unable to swallow the tablets, ruxolitinib may
be mixed to a suspension by adding the tablet to 40 ml of
water and stirring for 10 min before administration via nasogastric tube, followed by a flush with 75 ml of water. Administer the suspension within 6 hours of preparation.
The starting dose is based on a patients current platelet
count, and CBC should be monitored every 24 weeks
until the dose is stabilized, and then as needed.
Hold dose if platelet count is < 50,000 106/L; may restart,
possibly at a reduced dose, after platelet recovery.
Dose may be increased incrementally after at least 4 weeks
of therapy and no more frequently than every 2 weeks
to a maximum of 25 mg twice daily if an inadequate response has been achieved.
When used concomitantly with strong CYP3A4 inhibitors,
the recommended starting dose is 10 mg twice daily in
patients with a platelet count > 100,000 106/L. Avoid use
with strong CYP3A4 inhibitors in patients with a platelet
count < 100,000 106/L.
(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 10. Characteristics of Targeted Therapies (Continued)


Classification

Mechanism
of Action

Small
molecule
inhibitors
(cont.)

Drug

Route of
Administration

Indications

Side Effects

Ruxolitinib
(Jakafi)
(cont.)

Nursing Considerations
Dose adjustment is recommended in patients with creatinine clearance < 60 ml/min or hepatic impairment.
When discontinuing therapy for reasons other than thrombocytopenia, a gradual taper by 5 mg twice daily each
week should occur.
Patients are at an increased risk for herpes zoster infections and should be advised to seek treatment if symptoms present.
(Incyte Corp., 2012)

Sorafenib
(Nexavar)

PO

Treatment of unresectable hepatocellular


carcinoma and advanced renal cell carcinoma

Palmar-plantar erythrodysesthesia, rash, hypertension, myocardial infarction, mucositis, dyspepsia, increased lipase, increased amylase, diarrhea, nausea, vomiting,
decreased appetite, increased risk of bleeding,
peripheral neuropathy, GI
perforation, prolongation
of QT interval, hypophosphatemia, lymphopenia,
neutropenia, anemia

Doses should be taken at least 1 hour before or 2 hours after a meal.


Continue treatment until patients no longer benefit from
therapy or until unacceptable toxicity occurs.
Caution patients to avoid becoming pregnant during treatment and for 2 weeks after treatment has stopped.
Sorafenib has been shown to cause birth defects or fetal loss.
Use with carboplatin and paclitaxel is contraindicated in
patients with squamous cell lung cancer because of increased risk of mortality.
Sorafenib may increase activity of warfarin if taken concomitantly.
(Bayer Healthcare, 2011)

Decreases tumor cell proliferation and reduces tumor angiogenesis through


tyrosine kinase
inhibition

Sunitinib
(Sutent)

PO

Treatment of GIST after


disease progression
while on imatinib or intolerance to imatinib
Treatment of advanced
renal cell carcinoma
Treatment of progressive, well-differentiated, unresectable, locally advanced or metastatic pancreatic neuroendocrine tumors

Myelosuppression, hepatotoxicity, left ventricular dysfunction, hypothyroidism, diarrhea, constipation, nausea, vomiting,
mucositis, stomatitis, dyspepsia, skin discoloration,
rash, depigmentation of
hair, palmar-plantar erythrodysesthesia, fatigue, hypertension, bleeding, edema, QT prolongation, impaired wound healing, venous thromboembolism,
pancreatitis

Medication may be taken with or without food.


Obtain baseline ejection fraction prior to initiation of sunitinib.
Concomitant use with CYP3A4 inhibitors, such as grapefruit juice, or inducers may alter exposure to sunitinib.
Monitor and correct for hypomagnesemia and hypokalemia
to reduce risk of QT prolongation.
(Pfizer Inc., 2011)

87

(Continued on next page)

Chapter 4. Principles of Biotherapy

Multikinase inhibitor that is


believed to decrease tumor
cell signaling,
angiogenesis,
and apoptosis

88

Table 10. Characteristics of Targeted Therapies (Continued)

Small
molecule
inhibitors
(cont.)

Mechanism
of Action
Binds to the intracellular protein FKBP12, resulting in inhibition of mTOR,
causing an interruption of cell division

Drug
Temsirolimus (Torisel)

Route of
Administration
IV

Indications
Treatment of advanced
renal cell carcinoma

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Side Effects

Nursing Considerations

Rash, asthenia, mucositis,


nausea, edema, hypersensitivity reactions, anorexia,
myelosuppression, hyperglycemia, hyperlipidemia,
hypercholesterolemia, hypertriglyceridemia, elevated alkaline phosphatase,
elevated SCr, lymphopenia, hypophosphatemia,
elevated AST, ILD, opportunistic infections, bowel
perforation

Preparation requires use of manufacturer-provided diluent


and then additional dilution with NS.
Premedicate with prophylactic IV diphenhydramine 2550
mg (or similar antihistamine) approximately 30 min before
the start of each dose.
Hold dosing if platelet count < 75,000/mm3 or neutrophil
count < 1,000/mm3.
Dose reductions are required in patients with even mild hepatic impairment, and drug is contraindicated in patients
with bilirubin > 1.5 ULN.
Use with CYP3A4 inhibitors, including grapefruit juice, or
inducers may alter exposure to temsirolimus and should
be avoided or the dose adjusted if concomitant use is required.
Store in refrigerator.
Protect from light.
Prepare temsirolimus in PVC-free, non-DEHP glass bottles
or infusion bags and tubing.
Protect prepared product from light and administer through
an in-line filter of < 5 microns within 6 hours after dilution
in NS.
Hyperglycemia and hyperlipidemia are likely and may require treatment. Monitor lipid profiles.
Patients receiving additional anticoagulation may be at increased risk for bleeding.
Monitor for symptoms of radiographic changes of ILD.
Because of abnormal wound healing, use with caution in
the perioperative period.
Patients should avoid receiving live vaccines and having
close contact with those who have received live vaccines.
Bowel perforations may occur; promptly evaluate for fever,
abdominal pain, bloody stools, and acute abdomen.
Women of childbearing potential should be advised of the
potential hazard to the fetus and to avoid becoming pregnant during treatment.
Monitor renal function at baseline and throughout treatment.
(Wyeth Pharmaceuticals, 2011)

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 10. Characteristics of Targeted Therapies (Continued)


Classification
Small
molecule
inhibitors
(cont.)

Mechanism
of Action
Inhibits VEGF
and EGFR tyrosine kinase activity that interferes with endothelial cell migration, proliferation, and new
blood vessel
survival

Drug
Vandetanib
(Caprelsa)

Route of
Administration
PO

Indications

Side Effects

Nursing Considerations

Treatment of symptomatic or progressive, unresectable, locally advanced or metastatic multifocal medullary


thyroid cancer

QT prolongation, skin reactions, skin photosensitivity,


ILD, pneumonitis, ischemic
cardiovascular events,
hemorrhage, heart failure,
diarrhea, hypothyroidism,
hypertension, PRES, rash,
acne, nausea, headache,
fatigue, anorexia, abdominal pain

Caprelsa is available only through a restricted distribution


program requiring certification of prescribers and pharmacies.
Do not crush tablets.
If patients are unable to swallow tablets, the tablets can be
dispersed in 2 oz of noncarbonated water, stirred for approximately 10 min, and then swallowed immediately. Any
residue in the glass should be mixed with 4 oz of additional water and swallowed by patient.
Avoid skin exposure to crushed tablets.
Concomitant use with CYP3A4 inducers may increase exposure to vandetanib and should be avoided.
Use is contraindicated in patients with congenital QT prolongation.
Monitor and correct for hypocalcemia, hypomagnesemia,
and hypokalemia to reduce risk of QT prolongation.
Obtain ECG at baseline and recheck 24 weeks and 812
weeks after starting vandetanib, and then every 3 months
thereafter.
Avoid concomitant use of drugs that prolong QT interval, or
perform more frequent ECG monitoring if use is unavoidable.
Instruct patients to wear sunscreen and protective clothing
when exposed to sun.
(AstraZeneca Pharmaceuticals, 2011)

Chapter 4. Principles of Biotherapy


89

(Continued on next page)

90

Table 10. Characteristics of Targeted Therapies (Continued)

Small
molecule
inhibitors
(cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Inhibits the mutated form of


BRAF serine/
threonine kinase

Vemura
fenib
(Zelboraf)

PO

Treatment of unresectable melanoma or


melanoma containing
the BRAF V600E mutation

Hypersensitivity, cutaneous
squamous cell carcinoma,
skin reactions, QT prolongation, hepatotoxicity, photosensitivity, eye irritation,
new malignant melanoma
lesions, alopecia, pruritus,
hyperkeratosis, arthralgia,
fatigue, nausea, diarrhea,
headache

Doses should be taken approximately every 12 hours.


Drug may be taken with or without food.
Tablets should be swallowed whole with a glassful of water.
Do not crush or chew tablets.
Because of the risk of developing cutaneous squamous
cell carcinoma, patients should receive a dermatologic
evaluation prior to starting vemurafenib and then every 2
months thereafter.
Monitor and correct for hypocalcemia, hypomagnesemia,
and hypokalemia to reduce risk of QT prolongation.
ECG should be obtained at baseline, 15 days after the start
of treatment, monthly during the first three months of
treatment, and then at least every 3 months thereafter.
Avoid use in patients with a QTc > 500 ms, and hold therapy if QTc exceeds this time during treatment.
Instruct patients to avoid sun exposure and wear protective
clothing, sunscreen, and lip balm when outdoors.
Vemurafenib is a CYP1A2 and CYP2D6 inhibitor and CYP
3A4 inducer; avoid concomitant use with other medications metabolized by these enzymes because of the potential for altered metabolism.
Concomitant use with CYP3A4 inhibitors, including grapefruit juice, and inducers may alter exposure to vemurafenib.
(Genentech, Inc., 2011b)

Inhibits transmembrane signal transduction


in the Hedgehog
pathway responsible for cell development

Vismodegib (Erivedge)

PO

Treatment of metastatic basal cell carcinoma


or locally advanced
basal cell carcinoma
that has advanced following surgery or in
patients who are not
candidates for surgery
or radiation therapy

Muscle spasm, alopecia,


dysgeusia, weight loss, fatigue, diarrhea, anorexia, constipation, arthralgia,
vomiting

Drug may be taken with or without food.


Patients should swallow capsules whole. Do not crush or
chew.
Because of teratogenicity, determine pregnancy status of
women of childbearing age prior to starting therapy. Inform male patients of fetal risk, and instruct on use of
contraception during treatment.
Patients may not donate blood during treatment or for at
least 7 months after completing treatment.
Concomitant use with agents that reduce stomach acid,
such as a proton pump inhibitor or H2 antagonist, may reduce absorption of vismodegib.
(Genentech, Inc., 2012a)

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 10. Characteristics of Targeted Therapies (Continued)


Classification
Small
molecule
inhibitors
(cont.)

Mechanism
of Action
Acts as a soluble receptor and
binds to VEGFA, VEGF-B, and
placental growth
factor (known
as PIGF), leading to inhibition
of neovascularization and decreased vascular
permeability

Drug
Ziv-aflibercept (Zaltrap)

Route of
Administration
IV

Indications

Side Effects

Nursing Considerations

In combination with
5-fluorouracil, leucovorin, and irinotecan
in patients with metastatic colorectal cancer that is resistant or
progressing following
treatment with oxaliplatin-based therapy

Hemorrhage, GI perforation, impaired wound healing, fistula formation, hypertension, arterial thromboembolic events including transient ischemic attack, cerebrovascular accident, and angina, proteinuria, nephrotic syndrome,
thrombotic microangiopathy, neutropenia, infection,
thrombocytopenia, diarrhea, dehydration, PRES,
anorexia, stomatitis, abdominal pain, fatigue, elevated hepatic transaminases

Store in refrigerator, and keep vials in original container until time of use to protect from light.
Administer infusions over 1 hour through a 0.2 micron polyethersulfone filter prior to any of the other drugs used in
the chemotherapy regimen. Do not use with filters made
from polyvinylidene fluoride or nylon.
Do not use product if solution is anything other than clear,
colorless to pale yellow in color.
Discard unused product following initial one-time access
into vial.
Dilute in NS or D5W to a concentration of 0.68 mg/ml.
Do not administer mixed with other IV medications.
Diluted solution may be stored under refrigeration for up to
4 hours.
Hold dosing at least 4 weeks prior to elective surgery.
Hold dosing if recurrent or severe hypertension occurs, and
restart once blood pressure is controlled.
Monitor urine protein, and hold dosing if proteinuria > 2
g/24 hours; restart once proteinuria < 2 g/24 hours. Dose
reduction is recommended for recurrent proteinuria > 2
g/24 hours.
(Regeneron Pharmaceuticals, Inc., 2012)

Chapter 4. Principles of Biotherapy


91

ADCCantibody-dependent cellular cytotoxicity; ALKanaplastic lymphoma kinase; ALLacute lymphoblastic leukemia; ALTalanine aminotransferase; ASTaspartate transferase; BCR-ABLbreakpoint cluster region-Abelson; BRAFv-raf murine sarcoma viral oncogene homolog B; CBCcomplete blood count; CDcluster of differentiation; CHFcongestive heart failure; CHOPcyclophosphamide, doxorubicin, vincristine,
prednisone; CLLchronic lymphocytic leukemia; CMLchronic myeloid leukemia; CTLA-4cytotoxic T-lymphocyte antigen 4; CVPcyclophosphamide, vincristine, prednisone; DEHPdi-2-ethylhexyl phthalate; D5W
5% dextrose in water; ECGelectrocardiogram; EGFRepidermal growth factor receptor; EPHA2ephrin A2; FLTFms-related tyrosine kinase; GIgastrointestinal; GISTgastrointestinal stromal tumor; Hhistamine; HER2human epidermal growth factor receptor 2; IFNinterferon; ILinterleukin; ILDinterstitial lung disease; INRinternational normalized ratio; IVintravenous; JAKJanus-associated kinases; JCV
John Cunningham virus; KDRkinase insert domain receptor; KRASKirsten rat sarcoma viral oncogene homolog; LFTliver function test; LVEFleft ventricular ejection fraction; mCimillicurie; MDSmyelodysplastic syndrome; minminutes; MMEAmonomethyl auristatin E; msmillisecond; mTORmammalian target of rapamycin; NHLnon-Hodgkin lymphoma; NSnormal saline; NSCLCnon-small cell lung cancer; oz
ounces; PDGFRplatelet-derived growth factor receptor; Ph+Philadelphia chromosomepositive; POby mouth; PRESposterior reversible encephalopathy syndrome; PVCpolyvinyl chloride; QTcQT interval
corrected; RANKLreceptor activator of nuclear factor B ligand; REMSrisk evaluation and mitigation strategy; SCsubcutaneous; SCrserum creatinine; TLStumor lysis syndrome; TNFtumor necrosis factor;
ULNupper limit of normal; VEGFvascular endothelial growth factor; VGFVaccinia virus growth factor

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Figure 9. Common Terminology in Cell Signaling


Ligands: Molecules, such as growth factors, that activate receptors, such as growth factor
receptors, on the surface of the cell
Ligand binding: The process by which the ligand attaches to a specific receptor site and
activates the receptor, thereby activating the signaling pathway. This is similar to antigen-antibody binding.
Monomer: Single receptor, inactivated state
Dimerization: Activation of receptor through monomer pairing. Dimerization occurs between
two adjacent receptors that have bound ligands. That is, two monomers that are side by side
on the surface of the cell are paired and activated by the ligand. The joining activates a series
of signals.
Phosphorylation: Activation of a chemical process to initiate signaling, such as with tyrosine kinase
Heterodimerization: The pairing of two different ligand-bound receptors together, such as
Erb1 and Erb2
Homodimerization: The joining of two receptors of the same subtype, such as two Erb1
(HER1) receptors or two Erb2 (HER2), Erb3 (HER3), or Erb4 (HER4) receptors
Note. Based on information from Paul, 2008.

initiate on the ligands of the extracellular domain, sending a


signal through the transmembrane to intracellular tyrosine kinase and on to the nucleus of the cell.
(4) Tyrosine kinases modify themselves as well as other cellular proteins by putting phosphate molecules on the amino acid tyrosine.
(a) This activity is necessary for receptor signaling.
(b) Targeted therapies are directed toward specific molecules
(targets) along a cellular signaling pathway that is involved
in tumor growth, proliferation, and invasion.
(5) Targeted therapies moderate, control, and/or kill cancer cells
and work differently than either chemotherapy or radiation
therapy (see Figure 10).
(6) Therapies targeting intracellular pathways, or tyrosine kinase
receptors, are small molecules and, to date, mostly oral therapies. Because of the need for long-term inhibition of signaling,
chronic oral therapy represents the most rational approach to
dosing. Patients may develop drug resistance with kinase-targeted therapies. Examples:
(a) Erlotinib
(b) Sorafenib
(c) Sunitinib
(d) Imatinib
(7) Mammalian target of rapamycin (mTOR) kinase inhibition:
Temsirolimus
(8) BRAF V600E mutations: Vemurafenib
(9) Anaplastic lymphoma kinasepositive: Crizotinib
(10) Therapies targeting growth factor receptors in the extracellular
pathways are generally mAbs (see previous section).
2. Growth factors
a) Growth factors are produced by cells in all body tissues.
b) They are primarily responsible for initiating the complex cell signaling that is required to maintain cell viability and division.
c) These factors can influence cells in either a positive or negative way
that affects cell survival, apoptosis, and differentiation.
d) Growth factors bind with their specific receptors and initiate a cascade of intracellular signaling.
e) Examples of growth factors
(1) Epidermal growth factor (EGF), which binds to EGFR
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 4. Principles of Biotherapy

(2) VEGF, which binds to the vascular endothelial growth factor


receptor (VEGFR)
f) Redundancies exist in cell signaling. Several extracellular signals may
lead to the activation of the same pathway.
(1) The final response of the cell may differ depending on the response from the nucleus.
(2) Despite this redundancy with stimuli, the kinetics and extent of
activation may vary, leading to vastly different outcomes.
K. Angiogenesis and antiangiogenic agents (Keith & Simon, 2008; Oklu, Walker, Wicky, & Hesketh, 2010; Viale, 2007; Wilkes, 2007; Wisinski & Gradishar,
2011; Wujcik, 2011)
1. Angiogenesis is the development of new blood vessels. It is a complex,
multistep process that is required for a host of normal functions, including wound healing, tissue repair, reproduction, growth, and development.
2. Under normal circumstances, angiogenesis is tightly controlled by a balance of stimulators and inhibitors.
3. In malignant angiogenesis, that balance is upset, leading to irregular molecular and cellular events that contribute to tumor neovascularization.

Figure 10. Cancer Treatments: Mechanisms of Action

Note. Figure courtesy of the Institute for Medical Education & Research, Inc., June 22, 2012. Used with permission.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

4. In the context of tumors, angiogenesis refers to the growth of new vessels


within a tumor. The new vessels develop from the existing vascular network and provide a blood supply for the tumor.
5. Tumors are initially antiangiogenic, so there must be a factor, known as
an angiogenic switch, that makes them proangiogenic. This switch is what
turns on tumor angiogenesis.
a) Hypoxia activates intracellular molecules including the hypoxiainducible factor-1 (HIF-1) complex. HIF-1 activation causes upregulation of proangiogenic factors including VEGF, platelet-derived
growth factor, and nitric oxide synthase. HIF-1 is essential in inducing the angiogenic switch, changing the microenvironment from antiangiogenic to proangiogenic.
b) VEGF and basic fibroblast growth factor are circulating growth factors known to induce angiogenesis. Their presence has been reported to correlate with extent of disease, clinical status, and survival.
c) Endothelial cells line the vasculature of normal tissues. In a resting
state, they provide a homeostatic barrier that prevents the uncontrolled
extravasation of intravascular components and inhibits coagulation.
d) When a tumor begins to grow in normal tissue, tumor cells release
factors that elicit responses from the surrounding endothelium. The
result is vascular growth from normal tissue into the tumor.
e) Neovascularization contributes to tumor invasion and metastasis.
(1) Tumor vasculature is permeable and disorganized with a weak
basement membrane. These conditions facilitate the migration
of endothelial cells.
(2) VEGF can cause accumulation of endothelial cells and stimulate further tumor angiogenesis.
(3) Blood flow in tumors is sluggish, thus inducing hypoxia and
acidosis. Tumor hypoxia further induces tumor angiogenesis.
(4) Hypoxia and acidosis may contribute to chemotherapy and radiotherapy resistance because of lack of oxygen.
6. Other molecular pathways involved in tumor angiogenesis
a) Matrix metalloproteinases (MMPs) are involved in degrading the extracellular matrix components (ECM). In angiogenesis, MMPs invade
the ECM via new vessel formation and lead to proliferation and migration of tumor cells.
b) Tumor angiogenesis also affects the Notch receptor pathway. Notch surface cell receptors are involved in cell fate, cell differentiation, and cell
proliferation. Vascular endothelial cells express certain Notch receptors.
One type is needed for the vascular development of embryos but also is
upregulated in tumor vasculature. This process may be VEGF mediated.
7. Antiangiogenic agents
a) Mechanism of action: Antiangiogenic agents target the neovasculature of tumors to halt their growth, prevent tumor invasion, and preclude metastatic diffusion. Potentially, antiangiogenic agents are ideal for use with other cancer therapy modalities because they maximize the efficacy of the other therapies.
b) Side effects: Table 10 lists some of the side effects of antiangiogenic agents.

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Chapter 4. Principles of Biotherapy


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Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 5

Nursing Considerations in
Cancer Treatment
A. Ethical issues: The rapidly changing healthcare environment necessitates
that nurses be sensitive to ethical and legal issues. Issues arise in the care
of all patients, but the intensity is often greater in the cancer population
when patients, families, and healthcare professionals face potentially difficult moral choices.
1. Ethical issues related to cancer therapy
a) Healthcare realities that present potential ethical issues
(1) Major advances: Medical technology, increased expectations,
and changing moral attitudes combine to generate complex
ethical and legal problems related to cancer and palliative care
(Butts & Rich, 2012; Pavlish, Brown-Saltzman, Hersh, Shirk, &
Nudelman, 2011; Pendry, 2007; Smith et al., 2011). In particular, the use of life-sustaining measures may raise ethical questions when healthcare professionals
(a) Fail to discuss a patients wishes before a crisis developed
(b) Are reluctant or fail to communicate medical treatment
options with a grief-stricken family
(c) Fail to consider supportive care measures
(d) Experience moral distress related to personal values or biases.
(2) Changing healthcare environment: Staffing shortages, reallocation of resources, consolidation, and corporatization have resulted in growing administrative dominance over clinical practice
(Agency for Healthcare Research and Quality [AHRQ], 2013;
Centers for Medicare and Medicaid Services [CMS], 2013; Institute of Medicine, 2004; Pendry, 2007).
(3) Increasing numbers of underinsured and undocumented individuals: Even for people with health insurance, the need to
make copayments can lead to debt. Children and the working
poor are most affected by poor coverage. Also, some people
with insurance are unable to obtain reimbursement for certain
treatments, such as BMT or off-label use of medications (Brock,
2010; CMS, 2013).
(4) Increases in cultural diversity: Cultural and communication differences present a range of challenges, from discussion of diagnosis and prognosis to decisions about who will provide longterm care (AHRQ, 2013; Butts & Rich, 2012).
(5) Use of alternative therapies: Increasing use of complementary and alternative medicine, either in conjunction with or as a
substitute for conventional treatment, is the result of many factors, including the unpredictable nature of individual response
to cancer and its treatment, the individuals need for a sense
of control, belief in individual rights and determination, and
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cultural and spiritual beliefs (Butts & Rich, 2012; Cooley, 2010;
Fouladbakhsh, 2013).
(6) Expanded use of targeted therapies, discovery of genetic mutations, and increase in molecular testing: As personalized
therapies become more common, healthcare professionals
are expected to apply this knowledge to practice. Reimbursement for testing and services, extensive family history collection, and costs of targeted and biologic therapies offer more
challenges to patients, the healthcare system, and professionals (Bronchud, Foote, Giaccone, Olopade, & Workman, 2008;
Calzone, Masny, & Jenkins, 2010).
b) Ethical issues that oncology nurses face in daily practice (Pendry, 2007)
(1) End-of-life decisions
(2) Informed consent
(3) Patient autonomy and decision-making capacity
(4) The right to refuse treatment
(5) Undertreatment of pain
(6) The healthcare environment and reform
(7) Access to care
(8) Confidentiality
(9) Scientific integrity
(10) Intra-family conflicts
(11) Nurse-family conflicts
(12) Nurse-physician conflicts
(13) Physician-family conflicts
(14) Participation in clinical research
2. The Joint Commission (2011) requires accredited institutions to provide
access to an ethics consultation to assist in evaluating the decision-making capacity of an individual as well as to assist with problem resolution.
3. The ethical principles guiding decision making are summarized in Table 11.
Table 11. Ethical Principles
Principle

Description

Clinical Examples

Autonomy

Independent decision making by an individual in accordance with his or her


own best interest

Respecting an individuals choice even when different from ones


own
Providing supportive services

Nonmaleficence

The duty to do no harm

Providing complete information


Providing survivorship services
Recognizing professional limitations and seeking consultation/collaboration
Adhering to professional standards of care

Beneficence

The duty to act in the best interest of


the involved person

Personalizing care based on individual desires, culture, disease,


and other factors
Providing evidence-based care

Justice

Equitable distribution of available resources

Offering/providing treatment regardless of ability to pay, culture, or


socioeconomic status
Assisting with or referring for financial support

Veracity

Truth telling

Explaining treatment in understandable terms before it is initiated


Providing accurate information and educational materials

Fidelity

Faithfulness to promises made

Following up as promised
Providing survivorship care planning
Fostering collegiality

Note. Based on information from Beauchamp & Childress, 2009.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 5. Nursing Considerations in Cancer Treatment

B. Legal issues related to cancer therapy: Adhering to national, state, and institutional standards is a fundamental responsibility of all nurses (American
Nurses Association, 2010; Brown, Marcus, & Bales, in press; Sabatino, 2010).
1. The acts and standards guiding nursing practice
a) Nurse practice acts: State laws that define nursing performance in
fundamental terms for each state
b) ONSs Statement on the Scope and Standards of Oncology Nursing Practice:
Generalist and Advanced Practice (Brant & Wickham, 2013) describes the
minimum standard of care to which a patient with cancer is entitled.
c) Infusion Nursing Standards of Practice (Infusion Nurses Society, 2011)
describes the current standards of nursing practice for IV therapy.
d) Sources of institution-specific standards
(1) Standards of practice
(2) Nursing policy and procedure manuals
(3) Job descriptions
(4) IRB decisions
2. Common legal issues
a) Medication errors (see Section D: Patient Safety)
b) Documentation issues: The duty to keep accurate records is a fundamental nursing responsibility. The medical record is scrutinized in the
event of litigious action and is believed to reflect the care rendered
(American Society of Health-System Pharmacists [ASHP], 2011; Anderson & Townsend, 2010; Brock, 2010).
(1) Common documentation errors
(a) Omitting significant observations
(b) Failing to document the patients response to an intervention
(c) Failing to document patient teaching and understanding
(d) Failing to document what was taught and to whom
(2) Nursing actions to include in documentation
(a) Telephone conversations, particularly those in which the
nurse gives the patient instructions or advice
(b) Pertinent conversations with the patient, family, or other
caregivers
(c) Interagency referrals
(d) Cytotoxic drug administration: See Appendices 1 and 2.
(e) Treatment-related documentation including the following,
when applicable
i. Two unique patient identifiers (such as name, medical record number, or date of birth)
ii. Patient-specific measurements used to calculate doses (e.g., body surface area [BSA])
iii. Pertinent laboratory and diagnostic test results
iv. Date and time of therapy
v. Drug name, dose, route of administration, and infusion duration
vi. Volume and type of IV fluids administered
vii. Assessment of the IV site before, during, and after infusion
viii. Information about the infusion device (e.g., vein selection, needle size, type of device, infusion pump)
ix. Verification of IV access device patency, including presence of a blood return before, during, and after IV therapy
(f) Patient assessment and evaluation of the patient response
to and tolerance of treatment
(g) Patient and family education related to drugs received, toxicities, toxicity management, and follow-up care
(h) Post-treatment or discharge instructions
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

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c) Informed consent
(1) Process: Patients must give IC for treatment, enrollment in a
clinical trial, or participation in nursing research (Beauchamp
& Childress, 2009; Butts & Rich, 2012; Klimaszewski, in press;
Pojman, 2010). With the exception of research, each institution determines its own practice related to how and if a patient
must provide written IC before receiving antineoplastic medications (Jacobson et al., 2012). It is important to maintain consistency between policy and practice throughout the institution.
The following approaches have been used.
(a) The general hospital consent to treat document serves as
the signed permission to provide antineoplastic medications.
(b) The patient signs a consent form designed specifically for
the administration of antineoplastic medications and that
is part of the medical record.
(c) Some centers use a general procedure consent form for
antineoplastic medications.
(d) A specific form is not signed, but consent is documented
within the medical record.
(2) Requirements
(a) The IC document must state the right of the patient to refuse or discontinue treatment at any time.
(b) The IC document and, subsequently, physicians and nurses, must guarantee patients that ongoing support and care
will be provided if they decline or discontinue treatment
connected with the trial or research.
(c) Nurses and physicians have different but complementary
roles in the IC process.
(d) See Chapter 2 for additional information on the IC process and the nurses role.
C. Safety standards for antineoplastic administration
1. ASCO/ONS Chemotherapy Administration Safety Standards: In 2008, ASCO
and ONS began a collaboration to outline safety standards for the administration of chemotherapy (Jacobson et al., 2009).
a) Professionals from disciplines across health care were included in the
development process of this consensus document, which applies to
all practice settings and focuses on patient safety.
b) Standards address staffing-related issues, chemotherapy planning,
documentation, orders, preparation, education, administration, and
monitoring.
c) The standards are included in ASCOs Quality Oncology Practice Initiative (QOPI) program, which certifies hematology/oncology practices based on quality indicators.
d) The original standards and later revisions were published in the
Journal of Clinical Oncology, the Journal of Oncology Practice, and the
Oncology Nursing Forum (Jacobson et al., 2009, 2012; Neuss et al.,
2013).
e) For more information, visit www.ons.org/practice-resources/clinical
-practice/ascoons-chemotherapy-administration-safety-standards.
D. Patient safety: The nurse is the final checkpoint in the medication administration process. Strategies should be implemented to minimize the occurrence of medication errors.
1. Prevalence of medication errors
a) As reported by the Institute of Medicine (2004), 3.7% of inpatients
experienced an adverse event related to a medication error.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 5. Nursing Considerations in Cancer Treatment

b) Preventable adverse drug events have been found to cause one out
of five injuries or deaths to patients in hospitals (AHRQ, 2000; Leape
et al., 1991).
c) Weingart et al. (2010) studied errors related to oral chemotherapy using incident reports from seven comprehensive cancer centers, a literature and Internet search, U.S. Pharmacopeial Convention [USP]
reports, and pharmacy and incident reports from the authors own
center. The majority of errors resulted in a near-miss of a dose; 39.3%
involved inaccurate supply, which resulted in adverse drug events. Incidents derived from the literature and Internet search and the authors hospital incident reporting system showed a greater percentage of adverse drug events (73.1% and 58.8%, respectively) compared
with the other sources (Weingart et al., 2010).
2. Risks associated with the administration of cytotoxic agents (Schwappach & Wernli, 2010)
a) Toxicity
b) Low margin for dosing error (e.g., use of high-dose ablative therapy
leaves essentially no margin for error)
c) Widely varying dosages and administration schedules (doses and
schedules may be patient-specific)
d) Doses often are modified based on patients clinical status and response.
e) Complicated and varying medications, schedules, and regimens
3. Types of chemotherapy medication errors (ASHP, 2011; Schwappach &
Wernli, 2010; Sheridan-Leos, 2007; Weingart et al., 2010)
a) Administration of the wrong dose (under- or overdosing)
b) Schedule and timing errors
c) Use of the wrong drug
d) Infusion rate errors
e) Omission of drugs or hydration
f) Improper drug preparation
g) Route errors (e.g., intrathecal [IT] versus IV)
h) Administration to the wrong patient
i) Administration when laboratory values not appropriate
4. Factors contributing to medication errors in chemotherapy: Most medication errors are system-related and not attributable to individual negligence or misconduct (Schwappach & Wernli, 2010; Sheridan-Leos, 2007;
Weingart et al., 2010).
a) Stress
b) Understaffing
c) Lack of experience in administering chemotherapy
d) Unclear or ambiguous chemotherapy orders
e) Lack of experience in administering the specific chemotherapy drug
with which the error occurred
f) Fatigue
g) Illegible handwriting
h) Inaccessibility of information about chemotherapy drugs
i) Chemotherapy drug packaging or vial difficult to read or understand
j) Increasing number of complicated schedules and new drug combinations
5. Strategies for preventing medication errors (ASHP, 2011; Jacobson et
al., 2012)
a) Verify all pertinent clinical patient information, including patients
measured height and weight, laboratory results, and BSA.
b) Ensure that up-to-date drug information and other resources are readily available to clinicians.
c) Support institutional policy that prohibits verbal orders for chemotherapy.
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d) Use preprinted, standardized forms or computerized physician order entry to order cytotoxic drugs when possible.
e) Avoid the use of abbreviations, acronyms, coined names, and other
ambiguous methods of communicating drug information.
f) Provide ongoing education to patients about their medications, and
encourage them to ask questions and seek clarification before their
drugs are administered.
g) Ensure adherence to institutional policies and procedures.
h) Verify all chemotherapy doses, scheduling, and dosing calculations
(see Chapter 7). Support institutional policy for a systematic method of dose verification.
i) Review orders in an environment with minimal distractions.
j) Limit chemotherapy administration to RNs who are qualified by education and training.
k) Use standardized processes to verify and document the accuracy and
appropriateness of all chemotherapy doses.
6. Inadvertent IT administration: The inadvertent administration of vincristine and other drugs into the subarachnoid space (IT administration) has resulted in a number of tragic deaths around the world (Gilbar & Seger, 2012). Publications from the Joint Commission (2005),
WHO (2007), and the Institute for Safe Medication Practices (2006)
prompted institutions to reevaluate their preparation and delivery of
vinca alkaloids and of IT medications in general. A multidisciplinary
review of the process of drug preparation and administration is advised
in each practice setting.
a) The ASCO/ONS Chemotherapy Administration Safety Standards
(Jacobson et al., 2012) call for organizational policies related to
IT medications. These drugs should not be prepared with any other agents. Once prepared, they should be marked with a uniquely
identifiable medication label and stored in a separate container or
location from other drugs. All IT medications are to be delivered
to the patient only with other medications intended for administration into the CNS.
b) Special procedures should be followed for the administration of IT
medications. See Figure 11 for recommendations.
c) Both the Joint Commission and WHO recommended that vincristine
and other vinca alkaloids be diluted and administered IV via a minibag. Opponents to this approach have cited the risk of extravasation,
as many institutions have policies against the infusion of vesicant chemotherapy into a peripheral vein. Gilbar and Carrington (2006) reported that vinca alkaloids can be safely administered as low-volume,
short-term infusions with minibags. (See recommendations for administration of short-term IV infusions in Chapter 6.)
d) Bortezomib is another drug that is fatal when administered by the IT
route. Bortezomib is administered either by rapid IV push or by subcutaneous (SC) injection. The stability of bortezomib when diluted
in a minibag has not been established (Gilbar & Seger, 2012). Therefore, other processes to prevent the inadvertent IT administration of
bortezomib should be used.
E. Safe handling and disposal of hazardous drugs (HDs): Many drugs used in
the treatment of cancer are hazardous to healthcare workers. The term hazardous describes drugs that require special handling because occupational
exposure may cause adverse health effects. These effects occur because of
the inherent toxicities of the drugs (ASHP, 2006; NIOSH, 2004). According to the Occupational Safety and Health Administration (OSHA, 1999),
a safe level of occupational exposure to HDs is unknown, and no reliable
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Chapter 5. Nursing Considerations in Cancer Treatment

103

Figure 11. Recommendations to Prevent Errors With Intrathecal Chemotherapy Administration


Administer vincristine and other vinca alkaloids IV via a minibag (i.e., IV piggyback). The stability of bortezomib when diluted in a
minibag has not been established.
Vinca alkaloids and bortezomib should include a clear warning label: FOR INTRAVENOUS USE ONLYFATAL IF GIVEN BY OTHER ROUTES.
Vinca alkaloids and bortezomib should never be given in the same treatment room as intrathecal medications. For patients receiving
antineoplastic medications by multiple routes, it is highly recommended that they either receive them in different practice areas or on
different days.
Only healthcare providers who have received specialized educational programs should prescribe, prepare, transport, or administer
intrathecal chemotherapy.
Different connectors should be used, whenever possible, for medicines to be administered via the intrathecal and other parenteral
routes.
Institutions should establish a list of drugs that can and cannot be given intrathecally.
Orders for intrathecal chemotherapy should be written on a separate form than IV chemotherapy. Consider using an intrathecal chemotherapy order form.
Intrathecal chemotherapy should be prepared and delivered as close as possible to the time of administration.
Intrathecal chemotherapy should be packaged, transported, and stored in specifically designated containers separately from IV or
other drugs. Intrathecal drugs should be clearly labeled both on the syringe and outer container For Intrathecal Use.
Intrathecal chemotherapy should not be stored in patient care areas.
Conduct a time-out immediately preceding intrathecal chemotherapy administration, including a formal two-person checking procedure by a chemotherapy-competent nurse and at least one other chemotherapy-trained healthcare professional. Document verification of the right drug, dose, route, patient, and time.
Note. Based on information from Gilbar & Seger, 2012; Institute for Safe Medication Practices, 2006, 2012; Joint Commission, 2005; World Health Organization, 2007.
From Preventing Intrathecal Chemotherapy Errors: One Institutions Experience, by L.H. Smith, 2009, Clinical Journal of Oncology Nursing, 13, p. 345.
doi:10.1188/09.CJON.344-346. Copyright 2009 by the Oncology Nursing Society. Adapted with permission.

method of monitoring work-related exposure exists. Therefore, it is imperative that those who work with HDs adhere to practices designed to minimize occupational exposure.
1. Definition: ASHP (1990) provided the first definition of HDs [a)e)];
NIOSH (2004, 2010, 2012) subsequently refined the definition [f)]. Drugs
are considered hazardous if they demonstrate one or more of the following characteristics in humans or animals.
a) Carcinogenicity
b) Teratogenicity or developmental toxicity
c) Reproductive toxicity
d) Organ toxicity at low doses
e) Genotoxicity
f) New drugs similar in structure or toxicity to drugs classified as hazardous using the above criteria
2. Potential adverse health effects associated with occupational exposure:
Published evidence indicating the increased occurrence of cancer among
occupationally exposed nurses and other healthcare workers (Blair et
al., 2001; Gunnarsdottir, Aspelund, Karlsson, & Rafnsson, 1997; Hansen
& Olsen, 1994; Levin, Holly, & Seward, 1993; Martin, 2005) is limited
because of the failure to connect exposure to health outcomes. IARC
publishes independent assessments of the carcinogenic risks of chemicals and has identified 11 drugs and two combination chemotherapy
regimens used in cancer treatment as known human carcinogens. Other antineoplastic agents are classified as probable or possible carcinogens (see Table 12) (IARC, 2013).
a) Structural defects in a fetus because of occupational exposure during pregnancy (Hemminki, Kyyronen, & Lindbohm, 1985; Peelen,
Roeleveld, Heederik, Kromhout, & de Kort, 1999)
b) Adverse reproductive outcomes, including miscarriage (Lawson et al.,
2012), infertility (Fransman, Roeleveld, et al., 2007; Martin, 2005),
preterm births, and learning disabilities in offspring of nurses exposed to HDs during pregnancy (Martin, 2005)
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

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Table 12. Antineoplastic Agents Classified as Carcinogens


Exposure Risk

Agents

Arsenic trioxide
Azathioprine
Busulfan
Chlorambucil
Cyclophosphamide
ECB (etoposide, cisplatin, and bleomycin)
Etoposide
Melphalan
MOPP (mechlorethamine hydrochloride, vincristine,
procarbazine, and prednisone)
Semustine
Tamoxifen
Thiotepa
Treosulfan

Group 2A: Probably carcinogenic


to humans

Azacitidine
Carmustine
Cisplatin
Doxorubicin
Lomustine
Mechlorethamine hydrochloride
Procarbazine
Teniposide

Group 2B: Possibly carcinogenic to


humans

Amsacrine
Bleomycin
Dacarbazine
Daunorubicin
Mitomycin
Mitoxantrone
Streptozocin

Group 1: Carcinogenic to humans

Note. Based on information from International Agency for Research on Cancer, 2013.

c) Chromosomal damage in healthcare workers following exposure to


HDs (Bouraoui et al., 2011; El-Ebiary, Abuelfadl, & Sarhan, 2013; McDiarmid, Oliver, Roth, Rogers, & Escalante, 2010; Yoshida, Kosaka,
Tomika, & Kumagai, 2006)
d) Acute symptoms such as hair loss, abdominal pain, fatigue, nausea,
nasal irritation or sores, contact dermatitis, allergic reactions, skin injury, and eye injury (Baykal, Seren, & Sokmen, 2009; Constantinidis
et al., 2011)
3. Potential adverse health outcomes associated with occupational exposure to biotherapy agents: Limited data are available regarding the effects of occupational exposure to biologic agents. It is unclear whether the criteria in the definition of HDs are adequate for protein-based
drugs (Halsen & Krmer, 2011).
a) Most biologic agents do not affect DNA and do not cause genetic
changes.
b) Antiangiogenic agents pose a risk to a fetus (e.g., thalidomide, lenalidomide) (Celgene Corp., 2012).
c) Several targeted agents meet one or more of the criteria in the NIOSH
definition of HDs and should be handled as hazardous (e.g., handled
with personal protective equipment [PPE] and not crushed). These
include dasatinib, imatinib mesylate, nilotinib, pazopanib hydrochloride, sorafenib, sunitinib malate, and vorinostat (NIOSH, 2012).
d) mAbs: Based on mechanism of action, some mAbs may cause developmental toxicity, including alemtuzumab, bevacizumab, cetuximab,
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 5. Nursing Considerations in Cancer Treatment

panitumumab, rituximab, and trastuzumab (Halsen & Krmer, 2011);


however, NIOSH does not classify these agents as HDs.
e) Conjugated mAbs are hazardous because of the attached radioactive
isotopes (e.g., tositumomab) or toxins (e.g., brentuximab vedotin).
f) Many drugs used for non-oncology indications meet one or more of
the criteria for HDs and should be handled as HDs. These include
immunosuppressant agents, antivirals, several anticonvulsants, estrogens, progestins, and androgens.
g) A list of HDs is found in NIOSHs List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012, with periodic updates on the
NIOSH website at www.cdc.gov/niosh/topics/hazdrug.
4. Routes of exposure
a) Absorption through skin or mucous membranes following direct
drug contact or contact with surfaces or objects that are contaminated with HDs
(1) Many studies reported measurable levels of cytotoxic agents in
the urine of healthcare workers (Connor et al., 2010; Fransman,
Peelen, et al., 2007; Sottani, Porro, Comelli, Imbriani, & Minoia, 2010; Sugiura, Asano, Kinoshita, Tanimura, & Nabeshima,
2011; Yoshida et al., 2011), most likely from dermal absorption.
(2) Multiple studies have documented contamination of the environment with HDs in drug preparation areas, drug administration areas, and patient care areas (Konate et al., 2011; Kopp,
Schierl, & Nowak, 2013; Matsumoto et al., 2010; Siderov, Kirsa,
& McLauchlan, 2010; Sottani et al., 2010; Sottani, Porro, Imbriani, & Minoia, 2012; Sugiura et al., 2011; Touzin, Bussieres,
Langlois, & Lefebvre, 2009).
(3) Several researchers have reported drug contamination on the
outside of drug vials when delivered by the manufacturers (Connor et al., 2005; Favier, Gilles, Ardiet, & Latour, 2003; Fischer,
Groebmair, Herwig, Pfaller, & Schierl, 2010; Touzin, Bussires,
Langlois, Lefebvre, & Gallant, 2008; Zock, Soefje, & Rickabaugh, 2011). Cyclophosphamide, 5-FU, ifosfamide, and platinum have all been detected on vial exteriors using various sampling techniques. These findings indicate that nurses are at risk
for skin exposure if they do not wear PPE while handling unopened drug vials.
b) Injection from needlesticks or contaminated sharps (ASHP, 2006;
NIOSH, 2004)
c) Inhalation of drug aerosols, dust, or droplets (Harrison & Schultz,
2000; Kiffmeyer et al., 2002; Mason et al., 2005)
d) Ingestion of contaminated food, beverages, tobacco products, or other hand-to-mouth behavior (NIOSH, 2004)
5. Hierarchy of hazard controls aimed at reducing worker exposure (Connor, 2006)
a) Eliminate the hazard: The best way to protect workers from a hazardous exposure is to eliminate the hazard or substitute a less toxic substance for the hazardous material, but this is not feasible with
drug therapy.
b) Engineering controls: These are machines or equipment used to isolate or contain the hazard to reduce worker exposure.
c) Administrative controls: This third level of protection includes safe
handling policies, procedures, work practices, and education and
training of those responsible for HD handling.
d) PPE: The final level of protection, consisting of protective equipment
and garments designed for worker protection from HDs, places the
primary responsibility for protection on the worker.
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6. Guidelines regarding PPE


a) Apparel
(1) Gloves: Wear two pairs of disposable gloves that are powder free
and have been tested for use with HDs. The FDA requires permeation testing for gloves to be labeled as appropriate for use
with chemotherapy. The ASTM International (2013) standard
involves permeation testing with chemotherapy drugs from several chemical classes. Gloves must prevent HD permeation for
a minimum of 30 minutes. Results are printed on the glove box
or are available from the manufacturer. Several types of materials, such as latex, neoprene, nitrile, and polyurethane, are used
to make chemotherapy gloves. Tested latex gloves provide protection but should be used with caution because of the potential for latex sensitivity. Inspect gloves for physical defects before use. Remove and discard gloves immediately after use, if
a tear, puncture, or drug contact occurs, or after 30 minutes
of wear (ASHP, 2006; NIOSH, 2004; Wallemacq et al., 2006).
Wearing double gloves and removing them carefully reduces
the opportunity for exposure (NIOSH, 2008). Remove outer
gloves first, turning them inside out to prevent the contaminated outer surfaces from touching the inner gloves. Remove the
inner gloves last after discarding all contaminated items and
PPE. Do not reuse gloves.
(2) Gowns: Wear a disposable, lint-free gown made of a low-permeability fabric, such as polyethylene-coated materials (Connor,
2006). The gown should have a solid front, long sleeves, tight
cuffs, and back closure. The inner glove cuff is worn under the
gown cuff; the outer glove cuff extends over the gown cuff to
fully protect the skin. Discard the gown if it is knowingly contaminated, before leaving HD-handling areas, and when finished with HD handling. Gowns are meant for single use. Used
gowns should not be hung up or reapplied after removal. This
prevents transfer of drug contamination to the environment
and the workers clothing (NIOSH, 2008).
(3) Respirators: Wear a NIOSH-approved respirator (such as a nonpowered, air-purifying, particulate-filter respirator) when inhalation exposure is possible. Two examples are when administering an aerosolized HD or cleaning an HD spill. Consult the
safety data sheet (SDS) for the respirator appropriate to the situation (NIOSH, 2005). Surgical masks do not provide respiratory protection from HD aerosols.
(4) Eye and face protection: Wear a face shield or a combination
of mask and face shield that provides splash protection whenever HD splashing is possible.
b) Situations requiring PPE: Wear PPE whenever HDs might be released
into the environment, such as in the following situations (NIOSH,
2004).
(1) Handling any HD vials, ampules, or packaging materials
(2) Introducing or withdrawing needles or dispensing pins from
HD vials
(3) Transferring drugs from HD vials to other containers using needles or dispensing pins and syringes
(4) Opening ampules of HDs
(5) Expelling air from an HD-filled syringe
(6) Administering HDs by any route
(7) Spiking IV bags containing HDs and changing IV tubing
(8) Priming IV tubing with HDs
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 5. Nursing Considerations in Cancer Treatment

(9) Handling HD leakage from tubing, syringe, and connection sites


(10) Discontinuing infusions of HDs
(11) Disposing of HDs and items contaminated by HDs
(12) Handling the body fluids of a patient who had received HDs
in the past 48 hours
(13) Cleaning HD spills
(14) Touching any surface that is potentially contaminated with HD
residue
7. Storage and labeling
a) In clinical areas
(1) Store chemotherapy drug containers in a designated location
that limits exposure of healthcare workers and provides appropriate storage conditions (e.g., temperature and light).
(2) Use a distinct label on all HD containers to indicate the hazardous nature of the contents (OSHA, 1999).
(3) Have access to instructions (e.g., SDS) regarding what to do in
the event of accidental HD exposure.
(4) Check HD containers before taking them from the storage area
to ensure that the packaging is intact and to detect any leakage or breakage.
b) In the home (Polovich, 2011) (see Appendix 1)
(1) Keep HDs out of reach of children and pets.
(2) Store HDs in containers that provide protection from puncture or breakage.
(3) Label HD containers to indicate the hazardous nature of their
contents.
(4) Provide instructions listing the procedure for handling a damaged HD container.
(5) Store HDs in an area free of moisture and temperature extremes.
(6) Provide HD spill kits and instructions for their use.
(7) Give verbal and written instructions about handling and storing HDs and HD waste.
8. During compounding: Maintain sterile technique during the preparation
of parenteral drugs. USP (2008) issued standards for sterile products,
including HDs. The environment in which sterile HD preparation takes
place must meet all standards for ventilation, including air exchanges
per hour, particle counts, and negative pressure. For a full explanation
of the standards, refer to the USP document.
a) Chemotherapy drugs
(1) Prepare sterile cytotoxic drugs in a primary engineering control
(PEC) that protects parenteral doses from microbial contamination and the environment from HD contamination (ASHP,
2006; NIOSH, 2004; USP, 2008). The two main types of PECs
are biologic safety cabinets (BSCs) and compounding aseptic
containment isolators (CACIs). A BSC has an open front, inward airflow that creates an air barrier to prevent HD contamination from escaping, and downward high-efficiency particulate air (HEPA)-filtered airflow to minimize bacterial contamination of sterile preparations. A CACI is an enclosed cabinet
that does not allow air exchange with the environment except
through a HEPA filter, with attached sleeves and gloves through
which the operator performs drug manipulations. A PEC must
(a) Be located in an area that is physically separate from other preparation areas and be at negative pressure to an adjacent ante area (USP, 2008)
(b) Eliminate exhaust through a HEPA filter and ideally be vented to the outside (ASHP, 2006; NIOSH, 2004; USP, 2008)
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(c) Be used by individuals trained to employ techniques that


reduce contamination
(d) Be decontaminated at the end of drug preparation or immediately if a spill occurs
(e) Be serviced according to the manufacturers recommendations
(f) Be recertified after relocation, repair, filter replacement,
and/or every six months (National Sanitation Foundation,
2007; OSHA, 1999).
(g) The exhaust fan of a BSC should operate continuously except when the BSC is being repaired or moved. After the fan
has been off, the BSC should be decontaminated before use.
(2) When preparing unsterile HDs, such as oral drugs that require
compounding or crushing, an isolator intended for containment may be used (NIOSH, 2004). Decontaminate the PEC
following use.
(3) Wash hands before donning PPE.
(4) Wear chemotherapy-designated PPE.
(5) If desired, place a sterile, plastic-backed absorbent pad on the
work surface.
(6) Limit items placed in the PEC to avoid interfering with airflow
(ASHP, 2006).
(7) Use safe technique when opening ampules (ASHP, 2006).
(a) Clear fluid from the ampule neck.
(b) Tilt the ampule away from yourself.
(c) Wrap gauze or an alcohol pad around the neck of the ampule.
(d) Break the ampule in the direction away from yourself.
(e) Use a filtered needle to withdraw fluid.
(8) When reconstituting drugs from vials, avoid pressure buildup,
which can result in the release of drug aerosols. Use a closedsystem transfer device (CSTD) if available (NIOSH, 2004). According to NIOSH (2004), a CSTD is a drug transfer device
that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or
vapor concentrations outside the system (p. 44). CSTDs are
supplemental engineering controls and do not eliminate the
need for a PEC or PPE (NIOSH, 2004).
(9) Use tubing and syringes with Luer-lock fittings.
(10) Avoid overfilling syringes. An overfilled syringe may separate
from the plunger end (OSHA, 1999).
(11) Spike IV bags and prime tubing with compatible fluid before
adding cytotoxic drugs (ASHP, 2006; OSHA, 1999) or use a
CSTD to minimize leakage and exposure (Harrison, Peters, &
Bing, 2006; Sessink, Connor, Jorgenson, & Tyler, 2011; Siderov
et al., 2010; Yoshida et al., 2009). Glass IV bottles are discouraged for HDs because of the need for venting and the potential
for breakage, both of which can result in exposure.
(12) Place a label on each HD container that says Cytotoxic Drug
or a similar distinct warning.
(13) Wipe the outside of the HD container (e.g., syringe or IV bag)
with moist gauze before placing it in a sealable bag for transport. Avoid transferring HD contaminants to the outside of the
transport bag.
(14) Dispose of all material that has come into contact with an HD
in a waste container designated for cytotoxic waste.
(15) Remove and discard outer gloves and gown. Then remove inner gloves.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 5. Nursing Considerations in Cancer Treatment

(16) Wash hands with soap and water before touching anything or
leaving the work area.
b) Biotherapy drugs
(1) Use safe handling precautions (e.g., PEC and PPE) for biotherapy agents that are considered hazardous (NIOSH, 2004).
(2) A nuclear pharmacist prepares radiolabeled mAbs for infusion.
Note: Federal and state laws require that radiation safety warning signs designate the areas in which radioisotopes are stored
or used (Iwamoto, Haas, & Gosselin, 2012).
9. Transporting HDs (OSHA, 1999)
a) Transport syringes containing HDs in a sealed container with the Luer-lock end of the syringe capped. Do not transport syringes with attached needles.
b) Select a transport receptacle that can contain HD spillage if dropped
(e.g., a leakproof, zipper-lock bag), and add impervious packing material as necessary to avoid damage during transport.
c) Label the outermost HD receptacle with a distinct label to indicate
that its contents are hazardous.
d) Ensure that whoever transports HDs has access to a spill kit and is
trained in HD spill cleanup.
10. Safe handling precautions during administration (ASHP, 2006; OSHA,
1999; Polovich, 2011)
a) Always wear chemotherapy-designated PPE.
b) Work below eye level.
c) Ensure that a spill kit and chemotherapy waste container are available.
d) Use a CSTD or place a disposable, absorbent, plastic-backed pad on
the work area to absorb droplets of the drug that may spill.
e) Use a CSTD or place a gauze pad under the syringe at injection ports
to catch droplets during administration.
f) Use a CSTD or needles, syringes, and tubing with Luer-lock connectors.
g) If priming occurs at the administration site, prime IV tubing with
a fluid that does not contain the HD or by using the backflow
method.
h) After drug administration, remove the IV container with the tubing
attached (NIOSH, 2004; Polovich, 2011). Do not remove the spike
from IV containers or reuse tubing.
i) Use detergent and water or cleansing wipes to clean surfaces that
come into contact with HDs (Polovich, 2011).
j) Discard all HD-contaminated material and PPE in a designated chemotherapy waste container.
11. Special precautions for RIT: Special precautions are necessary to protect healthcare workers from exposure while caring for patients receiving
RIT. Radiation protection standards and regulations are determined by
the U.S. Nuclear Regulatory Commission (NRC), the FDA (radiopharmaceuticals), and state radiation regulatory agencies.
a) Occupational radiation exposure should be kept as low as reasonably
achievable. This requires close collaboration between the healthcare
team and the radiation safety officer (RSO). Three factors help provide protection (Iwamoto et al., 2012).
(1) Time: Limit the amount of time spent near the radioactive source.
Radiation exposure is directly proportional to the amount of
time spent near the source. After a patient receives RIT, the patient is considered the radioactive source.
(2) Distance: Maximize the amount of space between personnel and
the radioactive source. Radiation exposure decreases as the distance from the radioactive source increases.
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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(3) Shielding: Add a protective barrier between the radioactive


source and personnel. The type of shielding used depends on
the type of radiation.
b) Radiation monitoring devices are used to measure occupational exposure.
(1) Monitoring of personnel: Personnel monitoring is required by
law whether a patient is treated as an inpatient or outpatient.
A film badge is the most widely used monitoring device. Each
person caring for a patient receiving radiation therapy should
be assigned a film badge that is only worn within the work environment, is changed according to institutional guidelines, and
is not shared with anyone else (Iwamoto et al., 2012). A dosimeter is another kind of radiation monitoring device. It can be a
personal device or one that is shared after being reset.
(2) Monitoring of the environment: Environmental monitoring is
done with a survey meter that reacts to the presence of ionizing particles. After a course of inpatient RIT is completed and
before the room is cleaned, the RSO surveys the room, linens,
and trash.
12. Handling a patients body fluids
a) After chemotherapy
(1) Wear double chemotherapy-tested gloves and a disposable
gown when handling the blood, emesis, or excreta of a patient
for at least 48 hours after the patient has received chemotherapy. Wear a face shield if splashing is possible (NIOSH, 2004).
(2) For an incontinent patient, clean the patients skin well with
each diaper change. Apply a protective barrier ointment to the
skin of the patients diaper area to decrease the chance of skin
irritation from contact with drug metabolites (Polovich, 2011).
(3) Flush the toilet with the lid down after disposing of excreta from
a patient who has received HDs within the past 48 hours. When
a lid is not present, consider covering the open toilet with a plastic-backed pad to prevent splashing while flushing. Although
there is no research to support the effectiveness of double flushing in reducing contamination, it has been suggested in the past
(Brown et al., 2001; Welch & Silveira, 1997) and may be helpful
with low-volume-per-flush toilets (Polovich, 2011).
b) After RIT (Iwamoto et al., 2012)
(1) Institute standard precautions as previously described when
handling the patients body fluids (e.g., sweat, saliva, urine, feces, blood, semen, vaginal fluid). The duration of precautions
varies depending on the radionuclides half-life.
(2) Consult the RSO or nuclear pharmacist for precautions based
on the specific radioisotope.
13. Handling a patients linens
a) After chemotherapy (Polovich, 2011)
(1) To the extent possible, preclude the need for laundering linens and clothing by using disposable linens or leakproof pads
to contain HD-contaminated body fluids.
(2) If body fluids are present, use standard precautions when handling the linens of a patient who had received chemotherapy
within 48 hours.
(3) Handle HD-contaminated bed linens and clothing as follows.
(a) In the hospital setting
i. Handle linens with PPE and place into a leakproof bag.
ii. In most institutions, all linens are handled as contaminated by laundry personnel before washing.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 5. Nursing Considerations in Cancer Treatment

(b) In the home setting (Polovich, 2011) (see Appendix 1)


i. Wearing gloves, place contaminated linens into a washable pillowcase, separate from other items.
ii. Machine wash linens and cloth diapers twice in hot
water, with regular detergent, separately from other
household items.
iii. Discard disposable diapers in plastic bags to prevent
leakage.
iv. Discard used gloves in a chemotherapy waste container if available.
b) After RIT (Iwamoto et al., 2012)
(1) If body fluids are present, use standard precautions when handling the linens of a patient who has received RIT.
(2) Keep linens in the hospital room until surveyed and cleared by
the RSO or nuclear pharmacist.
14. Disposal of HDs and materials contaminated with HDs
a) In the hospital setting (NIOSH, 2004)
(1) Place soft contaminated materials into a sealable, leakproof bag
or a rigid chemotherapy waste container marked with a brightly
colored label that indicates the hazardous nature of the contents.
(2) Use puncture-proof containers for sharp or breakable items.
Dispose of needles and syringes intact; do not break or recap
needles or crush syringes.
(3) Seal containers when full.
(4) Do not dispose of drug-contaminated items in infectious waste
(red) containers. Some facilities autoclave or microwave these
materials (NIOSH, 2004; Smith, 2002), which does not deactivate HDs.
(5) Follow institutional policy regarding disposal of partial doses
of HDs when administration is interrupted.
(6) Only housekeeping personnel who have received instruction in
safe handling procedures should handle chemotherapy waste
containers. These personnel should wear gowns with cuffs and
a back closure and two pairs of disposable chemical-protective
gloves.
b) In the home setting (Polovich, 2011) (see Appendix 1)
(1) Some agencies that provide HDs arrange for proper disposal
of contaminated equipment.
(2) Follow all the instructions applicable to the hospital setting
except those related to handling the filled waste container (if
provided).
(3) Designate an area away from children and pets where filled containers are placed for pickup.
(4) Follow county and state regulations regarding the disposal of
chemotherapy wastes.
15. Procedures following acute HD exposure: Accidents, improper technique, faulty equipment, or negligence in PEC operation can lead to
exposure (OSHA, 1999).
a) Initial interventions
(1) In the event of skin exposure: Remove any contaminated garments and immediately wash contaminated skin with soap and
water. Refer to the SDS for agent-specific interventions.
(2) In case of eye exposure: Immediately flush the eye with saline
solution or water for at least 15 minutes (OSHA, 1999), then
seek emergency treatment. Ideally, each area where HDs are
handled should contain an eyewash station. An acceptable alternative is a sterile saline IV container connected to IV tubing.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(3) In the event of inhalation exposure, move away from the area
of exposure as quickly as possible. Depending on the severity of
symptoms, seek emergency treatment from an employee health
professional or emergency department. Refer to the SDS for
agent-specific interventions.
(4) For accidental ingestion, do not induce vomiting unless indicated in the SDS. Depending on the severity of symptoms, seek
emergency treatment from an employee health professional or
emergency department. Refer to the SDS for agent-specific interventions.
b) Reporting (Polovich, 2011)
(1) In case of employee exposure: Report HD exposure to the employee health department or as institutional policy requires.
(2) In case of patient exposure: Report the exposure as institutional policy requires. In addition, inform the patients healthcare
providers.
16. Spill management
a) Radioactive spills: In case of a spill of radiolabeled antibody or contamination with the radioactive body fluid of a patient recently treated with RIT (Iwamoto et al., 2012)
(1) Restrict access to the area and contact the RSO immediately. Never try to clean the area or touch the radioactive source.
Adhere to the principles of time, distance, and shielding (discussed previously in paragraph 11).
(2) Follow other applicable NRC guidelines.
b) HD spills: Consider any leak of HDs that is greater than a few drops a
spill. Spill kits must be available wherever HDs are stored, transported, prepared, or administered (see Figure 12). Train everyone who
works with HDs in spill cleanup. Individuals trained in handling hazardous materials (such as a Hazardous Materials Response Team)
should clean up large spills whenever possible (OSHA, 2004b). In
case of a spill involving an HD, follow these procedures.
(1) Assess the spill to determine the need for additional help with
cleanup.
(2) Immediately post signs warning others of the hazardous spill to
prevent them from exposure.
(3) Don two pairs of chemotherapy-designated gloves, a disposable
gown, and a face shield.
(4) Wear a NIOSH-approved respirator (OSHA, 2004c).
(5) Use appropriate items in the spill kit to contain the spill, such
as absorbent pads, cloths, or spill control pillows.

Figure 12. Contents of an Antineoplastic Spill Kit

Two pairs of disposable chemical-protective gloves (optional: a pair of utility gloves)


Low-permeability, disposable protective garments (coveralls or gown and shoe covers)
Face shield
Respirator
Absorbent, plastic-backed sheets or spill pads
Disposable towels (34)
At least two sealable thick plastic hazardous waste disposal bags with an appropriate warning label
A disposable scoop for collecting glass fragments and sharps
A puncture-resistant container for glass fragments
Note. Based on information from American Society of Health-System Pharmacists, 2006.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 5. Nursing Considerations in Cancer Treatment

(6) Clean up the spill according to its location and type. Access the
SDS for the spilled agent to determine if any inactivators are
recommended (Gonzalez & Massoomi, 2010).
(a) To clean up a spill on a hard surface (ASHP, 2006)
i. Wipe up liquids using absorbent pads or spill control pillows. Wipe up solids using wet absorbent pads.
ii. Pick up glass fragments using a small scoop or utility gloves worn over chemotherapy gloves. Do not use
hands to pick up sharps. Place all sharps in a puncture-proof container.
iii. Place puncture-proof container and contaminated materials into a leakproof waste bag. Seal the bag. Place
the sealed bag inside another bag, appropriately labeled as chemotherapy waste. For the moment, leave
the outer bag open.
iv. Clean the spill area thoroughly, from least contaminated to most contaminated areas, using detergent and
sodium hypochlorite solution (bleach) if appropriate, based on the surface. If using bleach, allow contact with the surface for at least 30 seconds and follow with a neutralizer (e.g., 1% sodium thiosulfate).
Rinse twice with clean water.
v. Use fresh detergent solution to wash any reusable
items used to clean up the spill and items located in
the spill area. Use water to rinse the washed items. Repeat the washing and rinsing.
vi. Remove PPE and place disposable items in the unsealed chemotherapy waste disposal bag.
vii. Seal the outer disposal bag and place it in a punctureproof chemotherapy waste container.
viii. Follow institutional or manufacturers guidelines regarding cleaning or maintenance of equipment (e.g.,
an IV pump).
ix. Dispose of all material used in the cleanup process according to institutional policy and federal, state, and
local laws (OSHA, 1999).
(b) To clean up a spill on a carpeted surface (note that carpet is
not recommended in HD administration areas) (ASHP, 2006)
i. Don PPE, including a NIOSH-approved respirator.
ii. Use absorbent powder, not absorbent towels, to absorb the spill.
iii. Use a small vacuum with a HEPA filter (Gonzalez &
Massoomi, 2010), reserved for HD cleanup only, to
remove the powder. Dispose of the collection bag as
chemotherapy waste. Clean the outside of the vacuum before storing.
iv. Clean the carpet as usual.
v. Follow guidelines for a spill on a hard surface to clean
and dispose of other contaminated items.
(c) To clean up a spill in a BSC or CACI (ASHP, 2006; OSHA,
1999)
i. Clean the spill according to the guidelines for a spill
on a hard surface. Complete cleanup by rinsing the
surface with sterile saline for irrigation.
ii. Include the drain spillage trough in washing efforts.
iii. If the spill contaminated the HEPA filter: Seal the
open front of a BSC in plastic. Label any type of PEC
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

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Chemotherapy Spill Cleanup


Video
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ChemoBio4thInteractive.pdf

114

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

as contaminated equipment. Schedule a PEC service


technician to change the HEPA filter. Ensure that the
PEC is not used before the filter is changed.
(d) To clean up a spill in the home setting: See Figure 13.
(7) Report and document the spill according to institutional policy: For any spill greater than a few drops, complete a report
about the spill and forward it to those specified by institutional policy (ASHP, 2006). Document the following.
(a) Name of the drug
(b) Approximate volume of spill
(c) How the spill occurred
(d) Spill management procedures followed
(e) The names of personnel, patients, and others exposed to
the spill
(f) A list of personnel notified of the spill
17. Requirements for policies regarding the handling of HDs: OSHA (2004a)
requires that employers provide a safe or healthful workplace. Employers must implement policies and procedures related to the safe handling
of HDs. Policies should address all aspects of handling these hazardous
chemicals to protect employees, patients, customers, and the environment from contamination. Such policies must (NIOSH, 2004)
a) Outline procedures to ensure the safe storage, transport, administration, and disposal of hazardous agents
b) Describe the procedure for identifying and updating the list of HDs
used in the facility
c) Require that all employees who handle HDs wear PPE
d) Mandate that HDs be prepared in a BSC, CACI, or containment isolator (USP, 2008)

Figure 13. Spill Kit Procedure for Home Use


(Please review this procedure with your nurse.)
1. Do not touch the spill with unprotected hands.
2. Open the spill kit and put on both pairs of gloves. If the bag or syringe with chemotherapy drugs has been broken or is leaking and
you have a catheter or implanted port in place, before cleaning the spill, disconnect the catheter from the tubing and flush and cap
it.
3. Put on the gown (closes in back), face shield, and respirator.
4. Use spill pillows to contain spillput around puddle to form a V.
5. Use the absorbent sheets to blot up as much of the drug as possible.
6. Put contaminated clean-up materials directly into the plastic bag contained in the kit. Do not lay them on unprotected surfaces.
7. Use the scoop and brush to collect any broken glass, sweeping toward the Vd spill pillows, and dispose of the glass in the box of
the kit.
8. While still wearing the protective gear, wash the area with dishwashing or laundry detergent and warm water, using disposable rags
or paper towels, and put them in the plastic bag with other waste. Rinse the area with clean water and dispose of the towels in the
same plastic bag.
9. Remove gloves, face shield, respirator, and gown and place them in the plastic bag. Put all contaminated materials, including the
spill kit box, into the second large plastic bag, and seal and label the bag with the hazardous waste label in the kit.
10. Wash your hands with soap and water.
11. Call the home health nurse, clinic, or doctors office promptly to report the spill. Plans need to be made to replace the spilled chemotherapy so that treatment can be completed. Arrangements will be made to have the waste material picked up or have you bring it to
the hospital for proper disposal.
12. If the spill occurs on sheets or clothing, wash the items in hot water, separate from other laundry. Wash clothing or bed linen contaminated with body wastes in the same manner.
13. Patients on 24-hour infusions should use a plastic-backed mattress pad to protect the mattress from contamination.
Following these procedures prevents undue exposure and ensures your safety. Call your nurse if you have any questions. Thank you.
Note. Based on information from National Institute for Occupational Safety and Health, 2004.
From Home Chemotherapy Safety Procedures, by C. Blecker, 1989, Oncology Nursing Forum, 16, p. 721. Copyright 1989 by the Oncology Nursing Society. Adapted with permission.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 5. Nursing Considerations in Cancer Treatment

e) Prohibit staff from eating, drinking, smoking, chewing gum, using tobacco, storing food, and applying cosmetics in areas where HDs are
prepared or administered
f) Mandate training for all employees who prepare, transport, or administer HDs or care for patients receiving these drugs. This training must include the risks of exposure and appropriate procedures
for minimizing exposure. The policy should describe how training is
documented (OSHA, 2012).
g) Require that documents such as SDSs are available to healthcare workers who handle HDs
h) State that spills should be managed according to the institutions HD
spill policy and procedure
i) Set forth a plan for medical surveillance of personnel handling HDs
j) Address HD handling around pregnant workers. Even when recommended precautions are used, the potential for accidental exposure cannot be eliminated (Connor et al., 2010; Schierl, Bhlandt,
& Nowak, 2009; Siderov et al., 2010; Turci et al., 2011). Developing
fetuses and newborn infants may be more susceptible to harm from
certain HDs. Therefore, an additional level of protection is suggested for those most vulnerable to the reproductive and developmental
effects of HDs. Employers must allow employees who are actively trying to conceive or are pregnant or breast-feeding to refrain from activities that may expose them and their fetus to reproductive health
hazards such as chemical, physical, or biologic agents. Alternate duty
that does not include HD preparation or administration must be
made available upon request to both men and women in the aforementioned situations or who have other medical reasons for avoiding exposure to HDs. The employee has the responsibility of notifying the employer of the specific situation (e.g., pregnancy, preconception, breast-feeding). The American College of Occupational and
Environmental Medicine (2011) provides guidelines for reproductive hazard management.
k) Define quality improvement programs that monitor compliance with
safe handling policies and procedures.

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Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 5. Nursing Considerations in Cancer Treatment


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Chapter 6

Administration
Considerations
A. Routes of administration
1. Oral: The use of oral antineoplastic agents is more common than in the past
and is likely to double in the next several years (Moody & Jackowski, 2010).
a) Advantages
(1) Convenience of home treatment
(2) Decreased time spent in outpatient or inpatient oncology departments
(3) Increased sense of control and independence for the patient
b) Disadvantages
(1) Can be expensive and may result in reimbursement- and insurance-related issues
(2) Patient difficulty in adhering to treatment regimen due to
(a) Difficulty swallowing medication
(b) Complex dosing and schedules
(3) Inconsistent absorption of agents
c) Potential complications
(1) Food-drug interactions (e.g., grapefruit juice can interfere with
a liver isoenzyme needed to metabolize medications) (Goodin, 2007)
(2) Drug-drug interactions resulting in excess toxicity or decreased
efficacy
(3) Incorrect dosing
(4) Patients continuing medications beyond the planned duration of treatment or despite side effects that necessitate holding treatment
d) Nursing implications (Moody & Jackowski, 2010)
(1) Verify the accurate dosing of oral anticancer therapy using the
same process as for IV chemotherapy.
(2) Wear PPE when administering hazardous oral agents.
(3) Do not crush hazardous oral agents outside of a BSC or other containment device. If a patient has difficulty swallowing or
has a feeding tube, ask the pharmacist to provide the drug in a
ready-to-administer form.
(4) Set up a schedule to monitor patients response to therapy, including follow-up laboratory testing and office visits.
e) Patient education for self-administration of oral therapy
(1) Provide verbal and written information about the drug(s), dose,
schedule, storage, and safe handling.
(2) Explain the scheduled days and times the medication should
be taken and dates of office visits and laboratory tests. A calendar is a useful tool for some patients.
(3) Emphasize side effects that should be reported immediately to
healthcare providers and any that require holding treatment.
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(4) Establish a process to evaluate patient adherence to therapy, including correct dose and schedule. For example,
(a) Make a scheduled phone call with the patient three to five
days after initiation of medication to assess compliance.
(b) Instruct the patient and family members to bring the medication schedule, calendar, and any other tool developed
to all follow-up appointments.
2. Subcutaneous: SC injection allows agents to be administered into the
SC tissue by piercing the epidermal and dermal layers of skin (Joanna
Briggs Institute, 2012).
a) Advantages
(1) Ease of administration
(2) Well tolerated
(3) Decreased side effects for some agents
b) Disadvantages
(1) Inconsistent absorption
(2) Patients with decreased adipose tissue have increased risk of
drug misplacement.
c) Potential complications
(1) Pain at injection site
(2) Infection
(3) Bleeding/bruising
d) Nursing implications
(1) Wear PPE.
(2) Most common site for SC injection is the abdomen; however,
avoid the umbilicus and scars.
(3) Monitor platelet count.
(4) Use the smallest needle possible. Some medications are in prepackaged syringes; follow manufacturers instructions.
(5) Rotate injection sites if multiple injections are needed.
3. Intramuscular (IM): IM injections are used to administer medication
deep into the muscle. The ventrogluteal muscle (anterior gluteal site)
is considered the thickest gluteal muscle, and use of this site has fewer
complications (Joanna Briggs Institute, 2012).
a) Advantage: Rapid absorption of medication
b) Disadvantages and potential complications
(1) Pain
(2) Infection
(3) Peripheral nerve damage/neuropathy
(4) Hematoma
(5) Tissue necrosis
(6) Permanent damage to sciatic nerve
c) Nursing implications (Joanna Briggs Institute, 2012)
(1) Wear PPE.
(2) Use the proper size needle to ensure that medication is delivered
into the muscle and not SC tissue, especially with obese patients.
(3) Choose appropriate site.
(4) Insert at 90 angle and pull back on syringe to ensure injection
is not near a blood vessel.
(5) Avoid massaging the site.
4. Intraperitoneal (IP): IP chemotherapy can be used to treat ovarian cancer, as well as other cancers that cause peritoneal seeding such as lowgrade gastrointestinal (GI) and appendiceal carcinomas (Marin, Oleszewski, & Muehlbauer, 2007). Combining IP chemotherapy with IV therapy may offer a survival benefit over IV therapy alone in select patients
with ovarian cancer (Potter & Held-Warmkessel, 2008). IP chemotherapy may be administered using a catheter or implanted IP port.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 6. Administration Considerations

a) Advantages (Potter & Held-Warmkessel, 2008)


(1) Chemotherapy agents are delivered directly into the peritoneal cavity, providing higher concentrations of drug to the tumor.
(2) Systemic absorption by diffusion causes prolonged exposure
to the tumor via capillary flow. Lower doses can potentially be
used, decreasing the systemic side effects and allowing for cyclic treatment over time.
(3) IP access devices can be used to remove excess fluid from the
peritoneal cavity, and family members can be taught how to do
this if needed (Camp-Sorrell, 2011).
b) Disadvantages (Potter & Held-Warmkessel, 2008)
(1) Only select patients with minimal disease are candidates for
IP therapy.
(2) Patients require a surgical procedure to place the peritoneal
catheter or IP port.
(3) Potential exists for catheter-related infection or complications
such as bowel obstruction, abdominal pain, or peritonitis.
(4) Frequent postural changes are required following infusion,
which may be difficult for patients with comorbid conditions
such as arthritis, musculoskeletal disorders, or previous surgeries.
c) Potential side effects (Almadrones, 2007; Camp-Sorrell, 2011)
(1) Abdominal pressure and distention related to large amounts of
fluids placed into the peritoneal space
(2) Increased bladder irritation due to abdominal fullness, which
results in increased urinary frequency
(3) Severe nausea and vomiting
(4) Decreased appetite related to the large fluid volume
(5) Dyspnea secondary to abdominal distention
(6) Bleeding
(7) Diarrhea
(8) Ileus
(9) Infection
(10) Intestinal perforation
(11) Anaphylaxis
d) Nursing implications
(1) Utilize PPE.
(2) Place the patient in semi-Fowler position (Camp-Sorrell, 2011;
Hydzik, 2007).
(3) Access the peritoneal port with a 19-gauge noncoring rightangle needle. Depending on the patients size, use a needle
length of 11.5 inches (Hydzik, 2007).
(4) Flush the port according to institutional policy and procedure.
(5) Evidence is lacking to support the warming of IP fluid; therefore,
IP solution can be administered at room temperature (CampSorrell, 2011; Hydzik, 2007). However, if the patient reports being cold, provide warm blankets (Hydzik, 2007).
(6) Rotate the patient side to side every 15 minutes for one hour
after infusion (Hydzik, 2007).
(7) Drain fluid from the peritoneal cavity following dwell time, if
ordered.
5. Intrathecal: IT chemotherapy is used for patients with central nervous
system malignancies, including primary brain tumors, metastasis to the
brain or leptomeninges from solid tumors, lymphoma, and leukemia
(Aiello-Laws & Rutledge, 2008).
a) IT route delivers chemotherapy directly into the cerebrospinal fluid.
b) Cerebrospinal fluid can be accessed by a surgically implanted ventricular reservoir (e.g., Ommaya) or by lumbar puncture.
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c) The most commonly used IT agents are methotrexate and cytarabine


(Aiello-Laws & Rutledge, 2008). Note: Vinca alkaloids, such as vincristine, are lethal if administered via the IT route and should never be
given IT because of severe neurologic toxicity, including coma and
death (Schulmeister, 2006). The majority of chemotherapy agents do
not have IT indications.
d) Advantages
(1) Direct and consistent drug levels in the cerebrospinal fluid
(2) Ability to access the cerebrospinal fluid for testing as well as to
administer opiates and other medications
e) Disadvantages
(1) Requires surgical procedure to place intraventricular device
(2) Lumbar puncture is an invasive procedure.
(3) Requires a physician or specialty-trained RN to administer chemotherapy.
f) Potential side effects
(1) Increased intracranial pressure
(2) Headaches
(3) Confusion
(4) Lethargy
(5) Nausea and vomiting
(6) Seizures
(7) Infection
g) Nursing implications
(1) Utilize PPE.
(2) Ensure that only preservative-free solutions are used for IT chemotherapy (Camp-Sorrell, 2011).
(3) IT chemotherapy must be labeled For Intrathecal Use Only.
Wraps or packages should be removed immediately prior to administration by the person administering the medication (AielloLaws & Rutledge, 2008).
(4) Perform a time-out or other procedure designed to verify that
IT is the intended route for the medication.
(5) Monitor the patient for the potential complications listed previously.
6. Intrapleural: Intrapleural chemotherapy is used to treat malignant pleural effusions, which can be caused by mesothelioma, other solid tumors,
and hematologic disorders that metastasize to the pleura (Polovich, 2011;
Shuey & Payne, 2005). Other treatments include repeated thoracentesis, pleurodesis with sclerosing agent, insertion of pleural catheter, surgical procedures, radiation, and systemic chemotherapy (Shuey & Payne,
2005; Walker & Bryden, 2010).
a) Advantages
(1) May prevent recurrence of malignant pleural effusions
(2) Multiple agents can be used as sclerosing agents, such as chemotherapy agents, antibiotics, talc, and biotherapy agents (Shuey
& Payne, 2005).
b) Disadvantages
(1) Requires insertion of a thoracotomy tube
(2) Must be performed by a physician
c) Potential side effects
(1) Pain
(2) Infection
(3) Pneumothorax
d) Nursing implications
(1) Utilize PPE.
(2) Maintain aseptic technique.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 6. Administration Considerations

(3) Position the patient in a sitting position, leaning forward over


a sturdy locked tray table with a pillow as a headrest (Shuey &
Payne, 2005).
(4) The effusion fluid must be completely drained from the pleural cavity before instillation of the agent.
(5) Allow the agent to remain for the prescribed dwell time if applicable. If fluid is drained, handle as contaminated fluid (Polovich, 2011).
(6) Observe for signs and symptoms of respiratory distress.
7. Intravesicular: Intravesicular chemotherapy is used to treat urinary bladder cancer (Washburn, 2007). The standard treatment for nonmuscle invasive bladder cancer is transurethral resection followed by intravesical
chemotherapy using bacillus Calmette-Gurin, thiotepa, mitomycin C,
or gemcitabine (Shelley et al., 2012). The urinary bladder is a perfect organ for regional therapy (Shen, Shen, Wientjes, ODonnell, & Au, 2008).
a) Advantages
(1) Delivery of chemotherapy agents directly into the bladder to
eliminate residual disease and prevent recurrence
(2) Avoids side effects of systemic chemotherapy
b) Disadvantage: Requires bladder catheter insertion
c) Potential side effects
(1) Urinary tract infection
(2) Cystitis
(3) Bladder contracture
(4) Urinary urgency
(5) Extravasation with vesicant administration
d) Nursing implications
(1) Utilize PPE including face shield (Washburn, 2007).
(2) Maintain sterile technique during catheter insertion.
(3) Monitor for signs of extravasation, especially pain (Washburn,
2007). If the patient has uncontrolled pain following use of a
vesicant agent, suspect extravasation. Drain the agent and urine,
and notify physician immediately.
(4) Follow physician orders or protocol for schedule and positioning of the patient and drainage of agent after instillation.
8. Intra-arterial: Intra-arterial infusion allows chemotherapy to be delivered
in higher concentrations directly into a tumor site (Matthews, Snell, &
Coats, 2006). According to Camp-Sorrell (2011), several agents can be
delivered via the intra-arterial route: cisplatin, doxorubicin, 5-FU, floxuridine, irinotecan, mitomycin, oxaliplatin, paclitaxel, protein-bound
paclitaxel, tumor necrosis factor, and vinblastine.
a) Common sites (Camp-Sorrell, 2011)
(1) Liver
(2) Head and neck
(3) Bone
b) The three types of arterial access devices are short-term catheters, implanted arterial ports, and implanted arterial pumps (Camp-Sorrell,
2011).
(1) Short-term catheters: A nontunneled percutaneous arterial
catheter is placed during an angiographic procedure. This is
usually done in an interventional radiology department under
local anesthesia (Barber & Fabugais-Nazario, 2003). The most
common sites for insertion are the femoral and brachial artery
(Camp-Sorrell, 2011).
(2) Implanted arterial ports: These are similar to venous ports, with
the catheter surgically implanted into an artery. They are accessed
when needed, using a noncoring needle (Camp-Sorrell, 2011).
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(3) Implanted arterial pumps: These are intended for long-term


use. The infusion rate of the pumps can be programmable or
set by the manufacturer (Camp-Sorrell, 2011).
c) Advantages (Camp-Sorrell, 2011)
(1) Higher exposure of the tumor site to the chemotherapy agent,
potentially resulting in greater tumor response and decreased
systemic side effects
(2) Avoidance of extensive surgical procedures and potential complications related to surgery (e.g., liver resection)
(3) Patients with liver metastasis may be surgical candidates after
treatment with intra-arterial chemotherapy.
d) Disadvantages
(1) Requires an invasive procedure performed by physician
(2) Requires specialized nursing care and education
(3) Not all patients are candidates for intra-arterial chemotherapy.
e) Potential side effects (Camp-Sorrell, 2011)
(1) Infection
(2) Catheter migration or dislodgment
(3) Occlusion and thrombosis
(4) Bleeding at catheter insertion site
(5) Device failure
f) Nursing implications
(1) Obtain specialized training to assess and monitor arterial catheters.
(2) Immediately following intra-arterial catheter insertion, assess
the involved limb for peripheral pulses, color, temperature,
numbness and tingling, and bleeding (Camp-Sorrell, 2011).
(3) Utilize PPE.
(4) Monitor for occlusions.
(5) Review and understand the different types of devices.
(6) Review and understand the flushing and dressing change protocols per institutional policy.
(7) Avoid using arterial access devices for routine blood sampling
(Camp-Sorrell, 2011).
9. IV: Most chemotherapy is currently administered by the IV route. IV drugs
are delivered by IV push, short-term infusion, or continuous infusion.
a) Advantages
(1) Consistent absorption
(2) Direct route into bloodstream
b) Disadvantages
(1) Increased patient and healthcare provider time, often in a
healthcare setting
(2) Damage to the peripheral veins may necessitate central venous
access.
c) Potential complications (Joanna Briggs Institute, 2012)
(1) Infiltration
(2) Pain
(3) Phlebitis/cellulitis
(4) Infection
(5) Thrombosis
d) Nursing implicationsPeripheral venous access
(1) Avoid the ventral surface of the wrist when starting peripheral
IVs because of increased pain and potential damage to the radial nerve. Use the nondominant arm whenever possible (Infusion Nurses Society, 2011).
(2) Avoid areas of flexion.
(3) Avoid using lower extremities.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 6. Administration Considerations

(4) Choose veins that are large, smooth, and pliable.


(5) Avoid using the arm of patients who have had axillary lymph
node dissection.
(6) Avoid using an established IV site that is more than 24 hours
old whenever possible. CDC recommendations (OGrady et al.,
2011) allow use of peripheral IVs for up to 96 hours, but that
recommendation is based on risk of catheter-related infection;
use of irritants or vesicants may shorten the useful life of a peripheral IV access device. Thoroughly assess any established IV
site prior to use.
(7) Perform hand hygiene, wear gloves, prepare site with antiseptic, allow skin to dry, and avoid touching the insertion site after applying antiseptic (OGrady et al., 2011).
(8) Use the smallest catheter possible to deliver the planned therapy. IV peripheral catheters range in gauges from 1428 and
lengths from 5/8 to 2 inches (Camp-Sorrell, 2011).
(9) Use a catheter equipped with a safety mechanism to avoid sharps
injury (Infusion Nurses Society, 2011).
(10) Perform venipuncture according to institutional policy and procedure. If unsuccessful, restart IV using a different site on the opposite arm, if possible, or proximal to the previous puncture site.
(11) The chemotherapy agents may be connected directly to the IV
catheter or to a line of compatible maintenance solution. Secure all connections with Luer-lock devices. Administer agents
according to institutional policy.
(12) Check for blood return prior to initiating chemotherapy. Do
not pinch the IV administration tubing to determine blood return because the vein can rupture. Aspirate with a syringe by
the lowest Y-site and clamp off fluid from the bag or use gravity
to check by lowering the IV bag below the patients IV site (Joanna Briggs Institute, 2012).
(13) Observe for swelling, burning, tightness, cool skin, skin color
change, and flow rate (Joanna Briggs Institute, 2012). If infiltration occurs, immediately stop infusion and restart IV using
a different site on the opposite arm, if possible, or proximal to
the previous puncture site.
10. Central venous catheters (CVCs): CVCs include percutaneous subclavian catheters, tunneled subclavian catheters, peripherally inserted central catheters, and implanted ports. Assess for catheter function and
patency prior to use by aspirating for a blood return. Catheter occlusion may occur as a result of extraluminal fibrin deposit or intraluminal thrombosis. Drug precipitate may cause a blockage when the catheter is not flushed adequately between agents (Cummings-Winfield &
Mushani-Kanji, 2008).
a) Implanted ports: Access with a noncoring needle following skin
preparation according to institutional policy. Select the appropriate needle length (0.52 inches) based on the depth of the port
(Camp-Sorrell, 2011). Stabilize the needle as needed, and cover the
insertion site with a transparent semipermeable membrane dressing (Infusion Nurses Society, 2011). Inspect the insertion site for
evidence of needle dislodgment, leakage of IV fluid, drainage, or
edema during infusions.
b) For all CVCs: Verify catheter placement and function either by x-ray
or fluoroscopic dye study prior to initial use per institutional guidelines. Check for blood return by aspiration. DO NOT administer cytotoxic agents in the absence of blood return. The following may help
to establish blood return (Camp-Sorrell, 2011).
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Chemotherapy Administration
Through an Implanted Port
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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(1) Attempt to flush with normal saline, and gently pull back. Reposition the patient. Ask the patient to cough and take a deep
breath.
(2) Obtain physician order for declotting procedure, and follow
institutional protocol.
(3) Use x-ray or dye study to confirm proper placement of CVC and
to rule out catheter malfunction or migration in the absence of
blood return, according to institutional policy.
11. Special considerations for vesicant administration
a) When administering a vesicant through a peripheral IV site
(1) Avoid using an IV pump or syringe pump to minimize pressure
on the vein (Infusion Nurses Society, 2011).
(2) Remain with the patient during the entire infusion (Sauerland,
Engelking, Wickham, & Corbi, 2006).
(3) Limit administration to IV push or short infusion lasting no longer than 3060 minutes (Sauerland et al., 2006).
(4) Verify blood return every 25 ml for IV push and every 510
minutes during a short infusion (Sauerland et al., 2006).
(5) Closely monitor for signs and symptoms of extravasation, such
as swelling, loss of blood return, and patients report of pain
or burning sensation. Confirming extravasation of vesicants
during chemotherapy administration can be difficult because
manifestations can vary from no immediate signs to pain, swelling, and loss of blood return, as well as differentiating extravasation from flare and recall reactions (Wickham, Engelking,
Sauerland, & Corbi, 2006).
(6) Discontinue vesicant administration at the first sign of extravasation.
b) When administering a vesicant through a central vascular access
device (VAD)
(1) Administer via IV push, short infusion, or continuous infusion,
as ordered.
(2) Verify blood return prior to, during, and after drug administration.
(3) Monitor the IV site throughout the infusion according to institutional policy.
(4) Discontinue vesicant administration at the first sign of extravasation.
c) Piggyback or short-term infusion
(1) Verify blood return and IV patency prior to hanging the infusion.
(2) Attach the secondary tubing to the injection port closest to the
patient using a needleless, Luer-lock connector (Infusion Nurses Society, 2011).
(3) Initiate flow rate according to the physician order, and observe
the patient for any reactions.
(4) Once the short infusion is complete, check vein patency and
flush the line with a compatible solution.
d) Continuous infusions: Used when a constant plasma concentration over
an extended period of time is desired (Joanna Briggs Institute, 2012)
(1) Central VADs are preferred.
(2) Connect directly to the IV access device or by secondary IV set
to a compatible line of maintenance solution, according to institutional policy.
(3) Secure connections with Luer-locking devices.
(4) Monitor the IV site throughout the infusion according to policy.
(5) When patients are discharged with a portable pump for home
infusion, ensure they are instructed on how to manage problems with the pump and infusion and on how and when the
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 6. Administration Considerations

infusion will be discontinued (e.g., in the home or infusion


center).
(6) Flush line at the completion of the infusion.
e) IV push: Refer to physician order or institutional guidelines for suggested IV push rates, diluents, and other drug-specific details.
(1) Free-flow method (side-arm technique) (Infusion Nurses Society, 2011)
(a) Attach the syringe with the drug at the injection port closest to the patient.
(b) Aspirate for blood to verify IV patency.
(c) Allow compatible IV solution to flow freely.
(d) Slowly administer the chemotherapy agent, allowing the
flush solution to dilute the drug. Unless otherwise indicated, administer the agent at a rate of 12 ml/min.
(e) If multiple agents are administered, flush with a compatible fluid between each agent and at the completion of the
infusion.
(2) Direct IV push method: Cytotoxic agents are administered IV
push directly into the IV device. Refer to institutional policy
and procedure.
(a) Establish venous access. Obtain a new access site when administering a vesicant via a peripheral vein (Infusion Nurses Society, 2011).
(b) Flush the line with sterile IV solution in a syringe, and verify blood return.
(c) Detach the flush syringe, and attach the syringe containing the chemotherapy agent.
(d) Slowly administer the agent, aspirating for blood return
every 25 ml.
(e) Upon completion, disconnect the syringe carefully, minimizing blood loss; the blood will contain the cytotoxic agent.
(f) Connect a syringe with sterile flush solution, and gently
flush the catheter.
(g) Cap or disconnect the IV access device, as indicated.
B. Adherence to therapy
1. With the increasing numbers of oral therapies available, adherence to
the prescribed medication regimen is a concern (Weingart et al., 2008).
2. Barriers to adherence (Barefoot, Blecher, & Emery, 2009; Jarvis, 2012;
Moody & Jackowski, 2010)
a) The individuals culturally based health beliefs. Disease causation
may be viewed from a biomedical, naturalistic, or magico-religious
perspective.
b) Cost of the medication, copayment
c) Where to obtain the drug (e.g., local versus specialty pharmacy)
d) Complexity of regimen
e) Health literacy
f) Patients physical condition (e.g., ability to swallow medications)
g) Side effects
h) Poor understanding of the importance of adherence or poor patientprovider relationship
i) Lack of acceptance of illness because of current state of feeling well
(asymptomatic)
j) Inadequate follow-up/missed appointments
3. Optimizing adherence (Anderson & Klemm, 2008; Barefoot et al., 2009;
Jacobson et al., 2012; Winkeljohn, 2010)
a) Provide patient education.
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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

b) Employ behavior modification for patient and family as necessary.


Engage the patient and family members in the treatment process.
c) Use reminder systems.
(1) Pill boxes
(2) Calendars
(3) Diaries
(4) Follow-up telephone calls
d) Discuss medications at each intervention.
e) Perform pill counts.
f) Include caregivers in all discussions.
C. Pretreatment nursing assessment: Assess and document the following information.
1. Patient history: Identify cancer diagnosis, past and present surgical procedures, radiation therapy, and hormonal agents.
a) Use of complementary and alternative medicine (CAM): Questioning in a nonthreatening manner may encourage patients to disclose the use of these therapies. CAM includes the following (National Center for Complementary and Alternative Medicine, 2013).
(1) Natural products such as vitamins and supplements
(2) Manipulative body-based practices such as chiropractic care
(3) Mind and body medicine such as meditation, yoga, and acupuncture
b) Allergies: Identify food, drug, and environmental allergies, including latex (Infusion Nurses Society, 2011). Document all allergies in
the medical record.
c) Past medical history: Identify underlying health issues, such as hypertension, diabetes, and cardiac and pulmonary disorders. Include any
psychiatric illness. Identify alcohol and substance abuse.
d) Medication review: Obtain an up-to-date list of medications. Include
all prescription, recreational, and over-the-counter medications and
herbal and vitamin supplements. This information is essential to address possible drug-drug and drug-herb interactions (Shelley, Sussman, Williams, Segal, & Crabtree, 2009).
e) Symptom review: Assess symptoms related to the cancer diagnosis,
treatment regimen, comorbidities, and psychological issues (Jakobsson, Ekman, & Ahlberg, 2008).
(1) Poorly controlled symptoms affect QOL (Roiland & Heidrich,
2011) and adherence to the treatment protocol. Use standardized forms or checklists to ensure thorough symptom assessment (Brem & Kumar, 2011; Williams, Williams, LaFaver-Roling, Johnson, & Williams, 2011).
(2) Review nutritional status. Diet affects treatment tolerance (Ralph,
Von Ah, Scheett, Hoverson, & Anderson, 2011). Make the appropriate recommendations and referrals.
f) Distress: Establish the need for interdisciplinary referrals such as social workers, counselors, or religious or spiritual providers.
(1) Assess family structure and dynamics, living conditions, and
caregivers.
(2) Determine practical concerns such as transportation, financial,
or insurance issues.
(3) Assess cultural issues that may influence the treatment plan.
(4) Identify religious beliefs or spiritual concerns that may affect
dietary and other requirements and restrictions.
(5) Screening tools
(a) Assess performance status by using an appropriate scale
(see Table 3).
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 6. Administration Considerations

2.

3.

4.

5.

(b) Assess and document pain using an age-appropriate pain


scale (e.g., FACES Pain Rating Scale, 010 numeric pain
rating scale, McGill Pain Questionnaire [National Initiative on Pain Control, n.d.]).
(c) Assess fatigue using the Brief Fatigue Inventory (Mendoza
et al., 1999), the Piper Fatigue Scale (Piper et al., 1998),
or the Schwartz Cancer Fatigue Scale (Schwartz, 1998).
Patient data
a) Measure and document height and weight. Compare to previous
weight, and address significant changes.
b) Obtain, review, and document current laboratory values that are pertinent to the specific antineoplastic agents (e.g., assessment of kidney
function prior to cisplatin) (Jacobson et al., 2012).
c) Review and document diagnostic tests that are pertinent to the specific antineoplastic agent (e.g., cardiac ejection fraction prior to doxorubicin).
d) Review diagnosis, tumor type, grade, and stage of current disease.
Cancer treatment during pregnancy: The most common malignancies
diagnosed during pregnancy are breast, cervical, thyroid, leukemia, lymphoma, and ovarian (Brewer, Kueck, & Runowicz, 2011).
a) Collaborate with a maternal-fetal medicine team prior to initiation
of treatment.
b) Assist the patient in evaluating the risks and benefits to mother and
unborn child (Rimes, Gano, Hahn, Ramirez, & Milbourne, 2006).
c) Establish accurate gestational age. Cytotoxic chemotherapy is harmful to the fetus during the first trimester. Chemotherapy is not recommended after 35 weeks to avoid delivery during a period of bone
marrow suppression and the lack of drug excretion from immature
fetal organs (Giacalone, Laffargue, & Bnos, 1999; Visco, Meyer, Xi,
& Brown, 2009).
d) Inform the patient that breast-feeding is contraindicated during chemotherapy.
Practices that promote safety during antineoplastic therapy: Using standardized orders, computerized physician order entry, and electronic medication administration records can reduce medication errors.
a) Advantages of electronic systems (Levy et al., 2011; Rogers, 2009)
(1) Provide improved legibility
(2) Provide alerts for missing orders, incorrect doses, and wrong
route, time, and schedule
(3) Promote continuity of care between inpatient and outpatient
departments
(4) Increase communication among healthcare providers
(5) Provide easy access to pertinent patient data related to chemotherapy administration (e.g., laboratory and diagnostic tests)
b) Directly involving the patient and family members in the administration of chemotherapy can serve as a safety mechanism. Future research may identify the best methods for patients and families to be
involved in safe chemotherapy administration (Schwappach, Hochreutener, & Wernli, 2010).
Treatment plan (Jacobson et al., 2012)
a) Review the prescribed treatment plan/protocol. Verify that orders are
written and signed by a qualified licensed independent practitioner.
b) Identify patients participating in a clinical trial, and confirm presence
of a signed IC form. Notify clinical trials nurse for additional information if needed (if applicable).
c) Confirm that IC was obtained for the chemotherapy treatment. Follow institutional policy related to the IC process.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

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Pretreatment Preparation for


Chemotherapy Administration
Video
To view videos download
ChemoBio4thInteractive.pdf

d) Read and scrutinize the entire chemotherapy order to ensure it is


complete. Complete chemotherapy orders include the following elements (Neuss et al., 2013).
(1) Two patient identifiers
(2) Date(s) of administration (schedule, treatment interval)
(3) Diagnosis
(4) Regimen name
(5) Planned duration of treatment
(6) Current cycle number
(7) Criteria to administer the chemotherapy/biotherapy (e.g., laboratory values, toxicity)
(8) Allergies
(9) Method of dose calculation
(10) Height, weight, and other variables used to calculate doses
(11) Name of chemotherapy and biotherapy agents using generic
names rather than brand names
(12) Drug dose
(13) Route and rate of administration
(14) Length of infusion (if applicable)
(15) Supportive care (e.g., premedications, hydration, growth factors)
(16) Sequence of administration, if applicable
e) Confirm the patients current, measured height and weight.
f) Have two individuals recalculate the BSA (or other method of dose
calculation) and dose, and compare with the prescribed dose. Follow
institutional policy regarding which personnel are considered qualified to participate in the double-check process (e.g., two chemotherapy-competent RNs, RN and pharmacist).
g) Determine if the chemotherapy agents have irritant or vesicant potential.
6. Treatment: Patient preparation
a) Inform the patient and family who will be administering the chemotherapy.
b) Verbally review the treatment plan with the patient and/or family
members.
c) Provide a detailed explanation to the patient, family, and/or caregivers of the prescribed chemotherapy agent or protocol, the route of
administration, and short- and long-term side effects and respond to
any questions or concerns.
d) Confirm the patients full name and second identifier, such as date
of birth or medical record number.
e) Notify the prescribing healthcare provider of any symptoms that may
require a change in the treatment plan.
f) Obtain baseline vital signs.
7. Treatment: Staff preparation
a) Assemble the appropriate PPE.
b) Obtain the necessary equipment based on route of administration
(e.g., infusion pump).
c) Ensure that a spill kit and emergency medications and equipment
are available.
d) Ensure that delivered products match the ordered drugs and are labeled appropriately with the following information (Neuss et al., 2013).
(1) Patients full name and second identifier (e.g., date of birth,
medical record number)
(2) Date of administration
(3) Full generic name of the agent
(4) Route of administration
(5) Total dose
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 6. Administration Considerations

(6) Total volume required to administer dose


(7) Date and time the drug was prepared and the expiration date
if not for immediate use. Some agents are unstable and must
be administered within a specific period of time.
8. Chemotherapy administration (Neuss et al., 2013)
a) Confirm the treatment plan with the patient prior to each treatment.
b) Wear PPE.
c) Double-check the drug(s), and document the verification process by
two designated approved healthcare providers.
(1) Confirm two patient identifiers.
(2) Confirm drug name, dose, volume, rate, route, and cycle number.
(3) Obtain two signatures.
(4) Confirm rate setting on infusion pump (when used).
d) Obtain consent from patient to begin treatment as per institutional
policy (Klimaszewski, 2008).
e) Initiate chemotherapy via the appropriate route.
f) Monitor patient during administration for immediate complications.
g) Document the drug administration and the patients response.
h) Provide education and written discharge instructions.
i) Confirm the follow-up plan with patient and/or family member.

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Chapter 6. Administration Considerations


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Chapter 7

Pretreatment Care
A. Patient education
1. Definitions
a) Patient education, as defined by the journal Patient Education and
Counseling, is a planned learning experience using a combination
of methods such as teaching, counseling, and behavior modification
techniques, which influence patients knowledge and health and illness behavior. Patient counseling is an individualized process involving guidance and collaborative problem-solving to help the patient
to better manage the health problem. Patient education and counseling involve an interactive process [that] assists patients to participate actively in their health care (Elsevier, n.d., Definitions para.).
b) Bastable, Gramet, Jacobs, and Sopczyk (2011) defined patient education as the process of helping patients learn healthcare behaviors to
incorporate into their lives with the ultimate goal of optimal health
and independence in self-care activities (pp. 1213).
c) Falvo (2011) stated that by definition, one cannot be a teacher unless there is a learner. Therefore, merely giving information to patients does not mean that learning has occurred. To be effective, information must be presented in a way that makes it relevant (p. 38).
2. Factors that affect patient teaching (Bastable et al., 2011; Blecher, 2004;
Rigdon, 2010)
a) The educators expertise regarding the information provided
b) The learners health literacy
c) The educators understanding of differences in individuals learning styles
d) The strategies available to the educator for patient education
e) The educator matching appropriate strategies to specific content
and learners
f) The educators ability to involve the individual in the learning process
3. Short-term outcomes of patient education (Blecher, 2004; Jacobson et
al., 2012)
a) Empowering active participation in health care
b) Explanation of diagnosis and treatment options
c) Verbalization of an understanding of the goals and duration of therapy
d) Identification of both short- and long-term signs and symptoms that
need to be reported
e) Demonstration of the ability to perform self-care and/or adapt to
potential limitations
f) Promotion of adaptive coping skills in a life-threatening condition
g) Autonomous decision making regarding treatment or no treatment
h) Identification and appropriate use of community resources
4. Long-term outcomes of patient education (Joint Commission, 2012a, 2012b)
a) Improved self-care behaviors
b) Improved health-related QOL
c) Decreased healthcare costs
d) Increased customer satisfaction
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e) Better-informed patients, thus lessening the chance of malpractice


claims
5. Methods of patient education (e.g., auditory, visual, return demonstration) should be selected based on patients preferences and abilities.
6. Barriers to patient education
a) Barriers to learning should be assessed on an individual basis. The
following are some common barriers to comprehension (Joint Commission, 2012a, 2012b; Mann, 2011).
(1) Lack of knowledge of diagnosis and treatment plan
(2) Differences in the expectations regarding the purpose of treatment
between the patient/significant other and the healthcare team
(3) Concerns or misconceptions about therapy due to prior experience or the experience of a friend or relative, which may dissuade the patient from undergoing treatment
(4) Language barriers
(5) Educational barriers
(6) Health literacy barriers
(7) Physical barriers: Pain; visual, hearing, and cognitive impairments; and inability to speak can interfere with patients comprehension.
(8) Psychosocial or emotional issues may create barriers to learning.
b) Methods of overcoming barriers
(1) Allow patients to express concerns, and attempt to manage
their anxiety.
(2) Manage physical barriers, such as pain, and ensure that learners have glasses, hearing aids, etc., as needed.
(3) Provide access to translators, either in person or through telecommunications. Note: Significant others are not recommended as translators because of role conflicts or inability to communicate complex medical terminology.
(4) Correct any misconceptions concerning diagnosis, treatment,
and follow-up care.
(5) Tailor teaching to the patients level of understanding.
(6) Assess patients individually, and present information at an appropriate level.
(7) Cancer-related Spanish-language educational literature is available through NCI at www.cancer.gov.
(8) Cancer-related literature for patients with low literacy is available through NCI at www.cancer.gov.
7. Scope of information:
a) Provide verbal information and written material that is easy to read. Encourage patients and family members to ask questions and actively listen.
b) Education should encompass the following (Castiglia, Drummond,
& Purden, 2011; Wilson, Mood, & Nordstrom, 2010).
(1) Names of the prescribed antineoplastic agents and the rationale for the use of each agent.
(2) Potential short- and long-term side effects of therapy
(3) Medications that will be used to alleviate some of the side effects
(4) When to call the physician or nurse
(5) How to contact the multidisciplinary team, including physicians, nurses, emergency department, scheduling office, and
support services
(6) Schedule for laboratory and follow-up visits
8. Documentation: Nurses need to assess and document patients understanding of content after education takes place to meet regulatory (i.e.,
Joint Commission) standards, manage risk, and enhance staff communication (Joint Commission, 2012a, 2012b; Negley, Ness, Fee-Schroeder,
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 7. Pretreatment Care

Kokal, & Voll, 2009). Documentation of understanding should include


patients ability to verbalize or demonstrate learning. It also should identify future needs for reinforcement of information. If patients cannot
comprehend the information or they refuse education, this also must
be documented, along with alternative plans. Methods to assess patient
understanding include the following.
a) Patient/significant other is able to verbalize an understanding of the
information presented, including the name(s) of the medication(s)
and the purpose of the therapy.
b) Patient/significant other can identify and verbalize key instructions
for self-care.
c) Patient/significant other can identify and verbalize symptoms/side
effects to report and whom to call.
d) Patient brings new prescriptions on a follow-up visit and correctly verbalizes the instructions for use.
e) Patient is able to perform a return demonstration on items such as
temperature monitoring and hand washing.
f) Patient/significant other is able to accurately verbalize dates and times
of the next follow-up visit.
g) For oral agents, the patient/significant other is able to verbalize the
name of the medication, correct procedure for administration (e.g.,
with or without food), and safe handling and disposal procedures.
B. Verification and maintenance of treatment as planned
1. The treatment plan
a) Maintaining the planned treatment schedule is important because
systemic cancer treatments often have a narrow margin of therapeutic benefit (Levine, 2010).
(1) Minor adjustments below therapeutic doses can result in decreased tumor response, whereas minor adjustments above therapeutic doses can result in increased toxicity without increased
benefit (Levine, 2010).
(2) To ensure optimal patient outcomes, the oncology nurse must
(a) Evaluate the appropriateness of the treatment plan for the
disease being treated. The pathology and stage of cancer
should be clear in the patient record.
i. Goals of therapy should be stated.
ii. The plan should include what cancer drugs are to be
given, at what frequency, and for what duration.
(b) Perform safety checks to ensure that the agents are given
as intended with appropriate premedications and supportive care measures (Jacobson et al., 2012).
(c) Verify that regimen-specific laboratory and other diagnostic measures are performed and evaluated as applicable
(Jacobson et al., 2012).
b) Maintaining a treatment plans dose intensity (total planned dose
over total planned period of time) is associated with improved patient survival, and higher dose intensity may improve tumor response and cure rates (Crivellari, Monfardini, Stragliotto, Marino,
& Aversa, 2007).
(1) Dose reductions and treatment delays often occur because of
toxicities such as febrile neutropenia (Weycker, Barron, Edelsberg, Kartashov, & Lyman, 2012).
(2) Appropriate use of growth factor support (e.g., filgrastim) can
reduce the occurrence of complications related to febrile neutropenia in patients on myelosuppressive chemotherapy (Quirion,
2009).
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(3) When potential toxicities are proactively addressed, dose reductions and delays may be prevented or minimized (Kawashima
et al., 2012).
c) Verification of cancer treatment orders is not as simple as knowing a
single recommended dose or maximum safe dose, as is true for many
non-oncology medications.
(1) Appropriate doses for a given chemotherapy may vary widely
depending on the indication and route.
(2) For example, depending on the condition being treated, doses of methotrexate may range from 2.5 mg orally to 8 g/m2 IV
with a requirement for leucovorin rescue and other supportive measures (Kalb, Strober, Weinstein, & Lebwohl, 2009; Warnick & Auger, 2009).
d) Institutional policies and procedures should detail the process for
regimen and dose verification for cancer treatment orders.
(1) Policies and procedures should clearly define the steps to take
when discrepancies, potentially inappropriate orders, or other
concerns arise (Jacobson et al., 2012).
(2) The oncology nurse evaluates the appropriateness of the treatment regimen considering the indication, route of administration, concomitant treatments, and other factors, including
any premedications and supportive care medications (Jacobson et al., 2012).
e) The oncology nurse works with the patient and the care team to ensure that treatments remain on schedule at planned doses.
(1) Assessment and teaching before, during, and after treatment with
appropriate follow-up regarding identified needs is important.
(2) Developing an education checklist for nurses can ensure standardized approach to patient education (Mueller & Glennon, 2007).
(3) Teaching should include information regarding symptom management strategies.
(4) Education regarding symptom management enables prompt
evaluation and treatment of potentially serious toxicities, such
as neutropenic fever (Hawley, Loney, & Wiece, 2011).
2. Concepts of dose intensity and dose-dense therapy
a) Dose intensity: Dose intensity refers to the amount of drug given over
a period of time (e.g., mg/m2/week) (NCI, n.d.). Maintaining dose
intensity ensures optimal exposure of the tumor to chemotherapy
agents. Treatment delays or dosage reductions decrease dose intensity.
b) Dose-dense therapy: A standard regimen that is given with less time between cycles is referred to as a dose-dense regimen (NCI, n.d.). Dosedense regimens increase dose intensity. The rationale for dose-dense
therapy is to minimize tumor regrowth between cycles (Bayraktar &
Arun, 2012). Myeloid growth factors reduce the severity and duration of neutropenia from myelosuppressive treatments, allowing for
reduced time between treatment cycles (Quirion, 2009).
c) Relative dose intensity (RDI) is a way of expressing the actual dose
intensity compared to the planned dose intensity. It is expressed as a
percentage derived by dividing the actual dose of chemotherapy given over a period of time by the planned dose of chemotherapy over
the planned period of time (Loibl et al., 2011).
(1) Example: The plan calls for 100 mg/m2 of an agent weekly for
four weeks.
(a) The patient receives 100 mg/m2 on weeks 1, 2, and 3, and
75 mg/m2 on week 4.
(b) The planned dose intensity was 400 mg/m2/4 weeks, or
100 mg/m2/week.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 7. Pretreatment Care

(c) The actual dose intensity was 375 mg/m2/4 weeks, or 94


mg/m2/week.
(d) Therefore, the RDI was 94% (375 divided by 400).
(2) A study of patients with metastatic breast cancer (N = 933) found
that an RDI of 85% or greater was an important factor in extending time to disease progression and increasing overall survival in patients receiving first-line anthracycline/taxane-based
therapy (Loibl et al., 2011).
(a) In the same study, dose reductions were primarily related
to toxicity. Dose delays were due to logistics and patient
desires (Loibl et al., 2011). This highlights the necessity of
patient education regarding the importance of maintaining the treatment plan.
(b) Providing supportive care measures as needed to maintain
dose intensity is extremely important to improving longterm survival.
(3) A 20-year study of patients with breast cancer (N = 386) treated with adjuvant chemotherapy found that when RDI fell below 65%, survival rates were similar to not having received chemotherapy at all (Lenhart, 2005).
3. Role of the nurse in verifying the treatment plan and schedule
a) Prior to initiating a cancer treatment regimen, the oncology nurse should
(1) Review the regimen and anticipated side effects.
(2) Verify that the ordered regimen is appropriate for the indication.
(3) If a nonstandard regimen or research protocol is used, ensure that a copy of the nonstandard regimen or research
protocol is available to verify the ordered regimen (Jacobson et al., 2012).
(4) Always verify orders against the known regimen or protocol.
Do not verify doses against a previous treatment that may have
been based on different clinical factors (e.g., renal function).
(5) Obtain clarification orders prior to initiating the cancer treatment regimen if there are aspects of the orders that are unclear
or can be interpreted in more than one way.
b) Verification includes
(1) Checking that prescribed doses are within the normal range
for the indication
(2) Ensuring appropriate time intervals between scheduled treatments
(3) Ensuring that the route, volume, and rate of infusion (as applicable) are clearly stated and appropriate
(4) Reviewing and documenting laboratory values and other factors that may require changes in treatment
(5) Ensuring that all questions regarding orders are addressed prior to preparation of chemotherapy.
c) Institutions must ensure that processes, tools, and technologies (i.e.,
calculators) are in place to enable appropriate verification of treatment regimens by the nurse (Jacobson et al., 2012).
d) The oncology nurse serves a critical role in preventing harm to patients by appropriately ensuring the verification process is completed.
(1) Errors that result in harm to patients may occur during the
ordering process. Factors independently associated with dosing errors include the use of carboplatin (requires complex
AUC [area under time-versus-concentration curve] calculations), regimens with three or more agents, and regimens
requiring modifications (e.g., for renal function) (Ranchon
et al., 2012).
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(2) Use of electronic ordering systems in which prescribers directly enter orders for chemotherapy regimens has the potential
to reduce transcription errors. However, it does not preclude
the need for two independent verifications of dose calculations.
e) Verbal and/or telephone orders for chemotherapy or modifications
to existing orders are not acceptable.
(1) An exception to this rule is an order to hold or stop chemotherapy (Jacobson et al., 2012).
(2) Faxed or electronically signed orders sent via email are acceptable as written orders (Jacobson et al., 2012). This is a safe method for addressing the home medications of a patient hospitalized during off-hours.
4. Verification of patient understanding of the treatment plan
a) See also Patient Education.
(1) Verify patient understanding of and IC for therapy prior to initiating treatment.
(a) IC must be documented in the patients record.
(b) The process for obtaining IC, including who is responsible and allowed to obtain IC, should be specified in institutional policies and procedures (Jacobson et al., 2012).
(2) Provide written information regarding plan of care in language
appropriate for the patient.
(3) Allow opportunities for questions and assessment of understanding.
(4) Ensure patient understanding of therapies to continue at home,
symptom management strategies, follow-up appointments, and
importance of compliance with the treatment plan and schedule.
b) Involving the patient in the plan of care and providing appropriate
education may reduce medication administration errors (Schwappach, Hochreutener, & Wernli, 2010).
(1) Include the patient in the verification process prior to each cycle of chemotherapy (Jacobson et al., 2012).
(2) Verify the prepared drug including the correct drug, dose, volume (as applicable), route, rate (as applicable), and appearance of medication.
(3) Verify the correct patient using two identifiers (e.g., full name
and date of birth) against both the orders and the prepared
drug at the point of administration.
5. Promoting continuity of care: Systems must be in place to ensure accurate and complete reporting of the treatment plan and history when the
patient moves from one healthcare setting to another (Jacobson et al.,
2012). A change of healthcare setting (e.g., if the patient is hospitalized
following a clinic visit) is not in itself a reason to stop or delay treatments,
as this may result in reduced RDI or suboptimal care. Incomplete or inaccurate communication during transition between care settings can lead
to treatment errors. Communication should include
a) Medication reconciliation: Communicating a list of all current medications, which can then be evaluated regarding whether to continue in the new care setting
b) A summary of prior cancer treatments and the current treatment plan
including, as applicable, the cycle number, day of treatment, etc. (Jacobson et al., 2012).
6. Verification of the chemotherapy and biotherapy orders: The nurse
must become familiar with the planned regimen and evaluate the need
for clarification or additional information before initiating treatment.
a) Treating facilities must provide the resources to meet this responsibility (Jacobson et al., 2012). This may be in the form of
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 7. Pretreatment Care

(1) Printed drug and regimen references that are updated regularly
(2) Online access to current evidence-based guidelines (e.g., National Comprehensive Cancer Network [NCCN] guidelines, www.
nccn.org) and drug-specific information (e.g., FDA, www.fda
.gov)
b) Use of step-by-step checklists may be helpful in designing doublecheck systems to prevent errors (White et al., 2010).
c) Institutions should consider standardized order sets for commonly
used regimens to reduce the chance of errors during the ordering
process (Jacobson et al., 2012).
d) Order sets should use generic drug names unless there are multiple
brands of the generic drug and a specific brand formulation is desired (Jacobson et al., 2012).
e) Unapproved abbreviations should not be used in order sets (Jacobson
et al., 2012). An example of unapproved abbreviations can be found
at the Joint Commissions Facts About the Official Do Not Use List
at www.jointcommission.org/assets/1/18/Do_Not_Use_List.pdf.
f) Complexity of treatment regimens increases the risk for mistakes and
ambiguity when orders are handwritten. Use of preprinted order sets
and computer ordering systems potentially can decrease the occurrence of ambiguous or incomplete orders (Jacobson et al., 2012).
g) Mechanisms must exist for the reporting, tracking, and analysis of
errors that occur related to cancer treatments. Although individual
practitioner competencies are important, many errors occur related
to system weaknesses (e.g., tolerance of unacceptable abbreviations).
h) Efforts should focus on identifying areas of high risk and designing
systems to reduce human error (Ashley et al., 2011).
7. Standard treatment regimens, research protocols, and tailored protocols
a) Standard treatment regimens: These are treatment regimens determined to be efficacious for a given cancer and patient condition. Specific agents with specified doses, routes, rates, and sequence are identified within the regimen. All of the agents in a regimen constitute
one cycle of treatment. The timing of cycles and planned number of
cycles is included within the standard treatment plan.
b) Investigational regimens: Researchers continue to investigate new
agents and new ways of giving and combining older agents with the
goal of improving tumor response to therapy or reducing the toxicity of therapy.
(1) When a research protocol is used, communication among team
members is imperative to ensure the protocol is followed exactly as written.
(2) Failure to follow the protocol exactly can lead to difficulty in
interpreting the research findings and possibly reduce the validity of findings (Ermete, 2012).
(3) If a research protocol is used at multiple centers, the same version of the protocol must be used at all sites (Mitchell & Smith,
in press).
c) Tailored or individualized protocols: With better understanding of
the interplay of tumor molecular biology, the role of genetics, and
other factors, some regimens are individualized for patients. Patientspecific and tumor-specific data guide the use of agents that are more
likely to have a positive effect while eliminating toxic agents not likely to be of benefit. Some examples include
(1) Testing breast cancer tumors for overexpression of HER2, which
predicts benefit from treatment with anti-HER2 drugs in addition to traditional chemotherapy (Viale & Yamamoto, 2008)
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(2) Testing colon cancer tumors for KRAS mutation, which predicts
benefit from use of anti-EGFR therapy
(3) Using the patients immune system to specifically target the tumor. Sipuleucel-T is prepared by taking a patients own white
cells via apheresis, priming these cells by exposure to a molecule commonly found in prostate cancer, and then reinfusing
the cells (Smart, 2010).
8. High-dose chemotherapy: Some chemotherapy regimens call for very
high doses of chemotherapy to achieve cure or enduring response.
a) Patients receiving these regimens require more supportive care (e.g.,
transfusions, growth factor support) because of severe myelosuppression and other toxicities.
b) Oncology nurses must be familiar with the assessment and supportive care required when giving high doses of chemotherapy (Brown
& Faltus, 2011).
(1) The risk of cardiac toxicity with cyclophosphamide increases significantly when given at high doses (Viale & Yamamoto, 2008).
(2) With administration of high doses of cytarabine, routine neurologic assessments are performed to detect early signs of cerebellar toxicity (Brown, 2010).
(3) High doses of methotrexate can be fatal if leucovorin is not given to help the body to eliminate the methotrexate. This is referred to as a leucovorin rescue.
(4) High-dose chemotherapy sometimes is used with the goal of myeloablation in preparation for hematopoietic progenitor stem
cell transplantation. Administration of myeloablative chemotherapy is highly complex and can be lethal. Nurses should be
prepared with the specialized knowledge and skills required in
caring for these patients before, during, and following transplantation (Brown & Faltus, 2011).
9. Verification of dose modifications: If standard doses are modified, the
rationale should be documented (Jacobson et al., 2012). This allows the
nurse to assess the appropriateness of dosing. Some reasons for dose
modification include comorbid conditions (e.g., renal failure), toxicities
from prior treatment, and other factors such as age and polypharmacy.
a) Older age: Chemotherapy regimens are sometimes modified or reduced in older adults because of presumed inability to tolerate standard doses as renal function declines with age.
(1) Age alone should not exclude consideration of chemotherapy.
(2) Actual comorbid conditions and functional status may be better indicators than age to determine the need for dosage modifications.
(a) Standard doses and combination regimens in older adult
patients with good performance status and without significant comorbidities may be appropriate (Aggarwal & Langer,
2012). Dose reductions, while reducing potential toxicities, may increase the risk for poor response to treatment.
(b) Adjuvant chemotherapy in patients age 7079 with nonsmall cell lung cancer has been well tolerated compared
to younger populations and in associated with improved
survival (Cuffe et al., 2012).
(c) Appropriate myeloid growth factor support may improve the
ability to maintain standard-dose regimens (Quirion, 2009).
b) Children and infants: In pediatric oncology, agents sometimes are
converted from standard BSA dosing (mg/m2) to weight-based dosing (mg/kg) (Levine, 2010).
(1) This may be done using the rule of 30 (30 kg = 1 m2).
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 7. Pretreatment Care

(2) The rationale is that BSA dosing may not be accurate or optimal
because of organ development in very young (younger than three
years) and small (less than 10 kg to less than 30 kg) children.
(a) High rates of ototoxicity (15%) with subsequent need for
hearing aids have occurred in infants treated with carboplatin and vincristine (N = 60) for retinoblastoma when
dosing was based on BSA. Previous studies in which mg/
kg dosing strategies were used did not result in significant
hearing loss (Leahey, 2012).
(b) BSA may be preferred at times. A study using weight-based
dosing of busulfan for allogeneic stem cell transplantation
in young children found inadequate tumor responses due
to underdosing. The childrens immune systems had recovered and rejected the transplants (Trigg, 2004).
(3) Safe administration of chemotherapy in a pediatric setting requires a specialized knowledge set. The Association of Pediatric Hematology/Oncology Nurses (APHON) provides resources for pediatric oncology nurses. APHON has developed a Pediatric Chemotherapy and Biotherapy Provider Program, which
standardizes nurses education regarding the administration of
chemotherapy and biotherapy to the pediatric population. For
more information, visit APHONs website at www.aphon.org.
c) Polypharmacy: Sometimes interactions between medications necessitate dosage adjustments or additional monitoring. This can occur
with primary treatment agents as well as supportive care medications.
(1) One example is aprepitant, a supportive care agent given
in combination with other drugs to prevent chemotherapyinduced nausea and vomiting (CINV) (Dunphy & Walker, 2010).
Because of the way aprepitant is metabolized, usage may affect
coadministered medications.
(a) Aprepitant increases the effect of corticosteroids, especially when they are administered orally. It may be advisable to
reduce corticosteroids when they are not part of the cancer treatment itself (Aapro & Walko, 2010).
(b) Aprepitant may affect warfarin sodium several days after
the last dose of aprepitant is given, and international normalized ratio (INR) should be closely monitored (Aapro
& Walko, 2010).
(c) Cisplatin, a highly emetogenic agent that typically calls for
aprepitant use, has been independently associated with elevations in INR (Yano et al., 2011).
(d) Aprepitant may increase the effect of some chemotherapy
agents (Bubalo et al., 2007).
(2) Drug interactions are common and often unavoidable. Nurses
must be cognizant of the possibility of drug interactions that
may alter the efficacy of drugs.
(a) Assess all medications for potential interactions, including
over-the-counter medications and CAM therapies (Jacobson et al., 2012).
(b) Evaluate allergies and prior hypersensitivity reactions (Jacobson et al., 2012).
(c) Consult with an oncology pharmacist if a patient is receiving multiple drugs for cancer therapy or has comorbid conditions such as diabetes or heart failure.
(d) Be aware of common antineoplastic drug-drug interactions
and have access to resources that enable safe nursing practice in medication administration (Daouphars et al., 2012).
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10. Verification of dose calculations


a) Institutional policies and procedures should specify the minimum
components required for order sets to be considered complete and
acceptable. Missing components should be addressed during the verification process and prior to drug preparation (Jacobson et al., 2012).
b) Errors in dose calculations may cause significant patient harm (Levine,
2010).
c) Two chemotherapy-competent individuals (e.g., nurses, pharmacists),
in addition to the ordering prescriber, should perform independent
double checks of dosage calculations and ensure that required components of chemotherapy orders are present (Jacobson et al., 2012).
(1) Independent calculations help to prevent bias errors. Each
person performs calculations independently, and the results
are compared.
(2) If the independent results are not consistent with the ordered
dose, the nurse needs to obtain clarification before preparing
the chemotherapy.
(3) Institutions must ensure that nurses verifying and administering cancer treatments are adequately trained in performing
calculations and other aspects of the verification process. Systems should be in place to confirm that verifications are done
and documented prior to preparation of chemotherapy (Jacobson et al., 2012).
(a) After initial competence (knowledge) and proficiency (ability to use the knowledge) of the nurse has been determined,
institutions must have processes to evaluate and document
continuing competence and proficiency at regular intervals (e.g., annually) (Jacobson et al., 2012).
(b) Development of proficiency checklists may be helpful in
this process (Crannell, 2012).
d) Weights and heights used for dose calculations must be measured
(not stated) values. Institutions may choose to state in policies and
procedures an acceptable time frame for measured values (e.g., up
to 24 hours prior to administration time).
11. How doses are calculated
a) Several methods of dosing may be used depending on the prescribed
agent. Some medications are prescribed with fixed initial doses (mg),
whereas others are dosed based on weight (mg/kg), BSA (mg/m2),
or AUC calculations that account for renal function (Levine, 2010).
b) Fixed doses: This means the prescribed dose does not require calculation based on patient size. Many oral agents are dosed in this manner.
(1) Verification entails ensuring that the ordered dose is appropriate for the condition being treated. The diagnosis and stage of
disease and prior treatments should be clearly documented in
the patient record (Jacobson et al., 2012).
(2) A standard starting dose (typical for the average patient) may
require modification based on comorbid conditions. Package
inserts often describe known conditions requiring dose modifications.
(3) The rationale for any dose modifications should be clearly stated in the patients record (Jacobson et al., 2012).
c) Weight-based dosing: Dosing is expressed as dose of drug per unit of
body weight (e.g., mg/kg). Doses are calculated using an accurately measured weight.
d) BSA-based dosing: Most cytotoxic chemotherapy drugs are dosed based
on BSA, or the estimated total area of a persons skin expressed in
square meters (m2). BSA should be calculated using a current meaCopyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 7. Pretreatment Care

sured height and weight, not a height and weight stated by the patient (Griggs et al., 2012).
(1) Advantages: The underlying assumption is that by incorporating both height and weight, BSA is a more reliable indicator
than weight alone for predicting pharmacokinetics.
(2) Disadvantages
(a) Increased complexity of dose calculations increases the
chance for medication errors.
(b) BSA dosing does not account for factors other than height
and weight that might influence pharmacokinetics, such
as age and gender (Jger et al., 2012). For example, a man
and woman who both have a BSA of 2.0 m2 may have vastly different renal and hepatic functions.
(c) In addition to the current use of clinical factors in modifying BSA-based doses, future strategies may incorporate
genotype and phenotype markers as well as therapeutic
drug monitoring to achieve optimal doses (Gao, Klumpen,
& Gurney, 2008).
(3) Despite the issues with BSA-based dosing, it remains the most
common method for dosing many chemotherapy agents. Nurses should be aware of drug-specific recommendations for dosage adjustments that account for patient variability such as renal and liver function.
(4) Several different formulas can be used for calculating BSA, each
yielding slightly different results. For this reason, it should be
clear which formula the prescriber used when calculating drug
doses (Jacobson et al., 2012).
(a) In the United States, the most commonly used formula is the Mosteller equation (see Figure 14) (Gaguski &
Karcheski, 2011). However, no evidence has shown that
one BSA formula is more advantageous than another
(Griggs et al., 2012).
(b) An advantage of the Mosteller equation is that it can be carried out with any calculator that has a square root function.
(5) Intentional modifications made to the BSA to obtain adjusted doses should be clearly stated. If an ideal or adjusted body
weight is used instead of actual weight to calculate BSA, this
should be indicated in the order and the rationale should be
clearly documented.
(6) Evidence no longer supports routinely adjusting doses downward for obesity with most chemotherapy agents.
(a) Dose reductions may result in reduced clinical benefit,
while dosing based on actual weight does not typically increase myelotoxicity.

Figure 14. Formulas for Determining Body Surface Area


Mosteller equation (most commonly used in the United States):

height in cm weight in kg
3,600

This formula is converted to inches and pounds as

height in inches weight in pounds


3,131

Note. Based on information from Kouno et al., 2003.

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(b) Obese patients have been observed to experience less profound myelosuppression compared to non-obese patients using actual weight for BSA-based dosing (Griggs et al., 2012).
(7) Institutional policies and procedures should specify acceptable
methods for calculating BSA (e.g., specifying that Mosteller
equation is to be used).
(a) Online calculators, handheld BSA calculators, or any other tools used to obtain BSA should be validated for accuracy prior to use.
(b) The tools used should be based on the same formula used
by the ordering provider.
(8) The nurse should be aware of medication-specific circumstances that affect dosing based on BSA.
(a) For example, vincristine is dosed based on BSA, but prescribers often cap the dose at a maximum of 2 mg regardless of BSA to reduce potential neurologic toxicities.
(b) This capped dose may be further reduced when coadministered with azole antifungal therapies (Harnicar, Adel, &
Jurcic, 2009).
e) Carboplatin and AUC-based dosing: AUC calculations are commonly used to determine carboplatin doses. AUC refers to the amount of
drug exposure over time or the total drug concentration in plasma
over a period of time (Gaguski & Karcheski, 2011).
(1) AUC dosing of carboplatin accounts for age, gender, weight,
and renal function. Carboplatin drug clearance is strongly correlated with renal function (Hiraike et al., 2011).
(2) The Calvert formula is typically used to determine the total dose
of carboplatin in milligrams (see Figure 15). The target AUC is
specified in the order.
(3) In practice, an estimated creatinine clearance (estCrCl) is used
with the Calvert formula rather than an actual glomerular filtration rate (GFR), which requires a 24-hour urine collection.
(4) The estCrCl is related to GFR and is used in calculating carboplatin doses.
(a) Example: The order calls for Carboplatin AUC 6.
(b) The calculated estCrCl is 50 ml/min.
(c) GFR + 25 (estCrCl + 25) = 50 + 25 = 75
(d) Target AUC 75 = 6 75 = 450 mg
(e) Carboplatin dose = 450 mg
(5) Several formulas, each yielding significantly different results,
exist for obtaining the value for estCrCl. Dosing errors can occur when a different formula is used than that intended by the
prescriber.
(6) The Cockcroft-Gault formula (see Figure 16) is the most commonly used in the United States to obtain estCrCl (Gaguski &
Karcheski, 2011).
(7) Generally, the formulas for estCrCl are reliable.
(a) Exceptions include emaciated and/or immobile patients
in whom actual GFR is typically lower than estCrCl.

Figure 15. Calvert Formula


Dose of carboplatin (mg) = (target AUC) (GFR + 25)
Total dose calculated is in mg, not mg/m2.
Note. Based on information from Calvert et al., 1989.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 7. Pretreatment Care

(b) Estimations may be inaccurate in patients with rapidly changing serum creatinine levels (Gaguski & Karcheski, 2011).
(c) For obese patients, evidence shows that use of actual GFR
may be preferred over an estimated value. If an estCrCl is
used in this population, the prescriber may choose to use
an adjusted weight or alternative formula to Cockcroft-Gault
to determine estCrCl (Nelson, Formica, Cooper, Schwartz,
& Rutherford, 2012).
(8) Importantly, changes in how laboratories determine serum
creatinine may result in underestimation of serum creatinine
when it is low.
(a) Use of these values may result in overestimated CrCl and
subsequent overdosing of carboplatin with risk of increased
toxicity without added clinical benefit (Smart, 2011).
(b) For this reason, the FDA has recommended capping estCrCl at 125 ml/min in patients with normal renal function.
See Figure 17 for examples of dose capping. Dose capping
is not required when an actual GFR is used in calculating
the carboplatin dose (Smart, 2011).
(9) Patients with high GFR (measured, not estimated) may require
dose adjustments to minimize toxicity. However, this is an area
where a standardized approach is still controversial (Roy et al.,
2011).
(10) The rationale and choice of any calculation modifications should
always be clearly documented to enable the verification process
(Jacobson et al., 2012).
12. When calculations do not agree
a) Several factors can result in verification calculations yielding results
different from the ordered doses.
(1) A change in the patients weight: Minor weight changes typically are not significant. However, patients should be weighed

Figure 16. Calculation of Glomerular Filtration Rate: Cockcroft-Gault Method

Males:
estCrCl (ml/min) = (140 age) (weight in kg)
72 serum creatinine (mg/dl)
Females:
estCrCl (ml/min) = (140 age) (weight in kg) (0.85)
72 serum creatinine (mg/dl)

estCrClestimated creatinine clearance


Note. Based on information from Cockcroft & Gault, 1976.

Figure 17. Carboplatin Dose Capping Using Estimated Creatinine Clearance


Dose of carboplatin (mg) = (target AUC) (estCrCl + 25)
estCrCl capped at 125 ml/min
Maximum doses for sample target AUCs:
Target AUC 6: Maximum carboplatin dose = 6 (125 + 25) = 900 mg
Target AUC 5: Maximum carboplatin dose = 5 (125 + 25) = 750 mg
Target AUC 4: Maximum carboplatin dose = 4 (125 + 25) = 600 mg
AUCarea under the concentration-versus-time curve; estCrClestimated creatinine clearance
Note. Based on information from Calvert et al., 1989; Smart, 2011.

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before each treatment cycle and the doses calculated based on


the current weight.
(2) Using different formulas for verifying calculations
(3) An error in calculations during the ordering process
(4) An error in the calculations during the verification process.
The first step when noting discrepancies in doses is to recheck
the calculations.
b) Policy should indicate if rounding of doses is acceptable or expected.
c) Policies and procedures should dictate the acceptable variance between the ordered dose and the recalculated or rounded dose. For
example, a 5% variance rule is common practice (Levine, 2010). With
this, as long as the recalculated or rounded dose is within 5% of the
actual ordered dose, it is acceptable to proceed. Some facilities accept a variance up to 10% (Gaguski & Karcheski, 2011).
(1) When the ordered dose is 100 mg, a 5% variance rule allows
administration of the drug when recalculations fall between
95 mg and 105 mg. With a 10% variance rule and a 100 mg ordered dose, administration is allowed when recalculations fall
between 90 mg and 110 mg.
(2) Without a policy that states an acceptable variance, the nurse
must clarify any dose discrepancy with the prescriber before administering treatment.
(3) It is not in the oncology nurses scope of practice to determine
acceptable variance without policies and procedures guiding
the process.
13. Verification of medication sequence
a) The order in which chemotherapy and biotherapy agents are given may affect the pharmacokinetics and pharmacodynamics of the
agents. However, it is not always known if specific sequences of treatments result in better outcomes.
b) A review of published studies evaluating 35 different chemotherapy combination sequences found only 14 combinations in which
sequence did not seem to have an impact relative to toxicity or
clinical benefit. For the remaining 21 combination regimens, improper sequencing of the chemotherapy agents demonstrated the
potential for increasing toxicity or decreasing the effectiveness of
the regimen (Mancini & Modlin, 2011). The following are some
examples.
(1) Paclitaxel should be given before cisplatin, as the reverse is
known to cause more severe neutropenia without increasing
the effectiveness of the regimen (Mancini & Modlin, 2011).
(2) For the treatment of non-small cell lung cancer, cisplatin should
be given before irinotecan because this sequence has demonstrated more favorable tumor response rates without increased
toxicity (Han et al., 2006).
c) The sequence of administration should be stated in the chemotherapy orders (Jacobson et al., 2012).
d) Some institutions develop algorithms or charts to assist staff in determining administration sequence when no specific direction is given
in the chemotherapy orders.
(1) As new research and medications become available, these tools
should be updated to reflect the most current evidence.
(2) In the absence of specific policy-driven direction, the nurse
should seek clarification of sequence from the ordering provider when the orders are not clear.
14. Verification of oral agents
a) See also Appendix 3.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 7. Pretreatment Care

b) Oral formulations of chemotherapy and biologic agents require the


same processes of verification as other types of systemic cancer treatments. ASCO/ONS have published specific safety standards to address the growing use of oral agents (Neuss et al., 2013).
c) Many oral agents are based on fixed dosing regimens, but some require dose calculations.
d) Ensuring patient/caregiver understanding of the oral treatment regimen is critical when the agents are administered at home.
e) Some patients do not adhere to treatment regimens because of a
lack of understanding or inadequate preparation (Simchowitz et
al., 2010).
f) Retail pharmacists are not always familiar with oral cancer medications and may not have the background to provide adequate patient
education (Simchowitz et al., 2010).
g) Complex treatment schedules may make it difficult for some patients
to maintain adherence. Continuing follow-up (e.g., phone calls) and
providing treatment calendars may be helpful.
h) Failure to adhere to the treatment regimen may result in worse outcomes.
(1) For example, rapid tumor progression and resistance can occur
after only short periods of abstaining from kinase inhibitors such
as imatinib. Patient education should include the importance of
maintaining the regimen as ordered (Barnes & Reinke, 2011).
(2) This highlights the importance of ensuring communication of
the treatment plan between healthcare settings. Cancer therapies should not be stopped solely because of a change in healthcare setting.

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Chapter 8

Infusion-Related
Complications
A. Types of infusion complications: The oncology nurse must be alert for immediate complications of cytotoxic therapy. This section covers complications that patients may experience during or shortly after chemotherapy administration. Terms used include
1. Extravasation: A passage or escape into the tissues; passage or escape of
antineoplastic chemotherapeutic drugs into tissue (Mosbys Dictionary of
Medicine, Nursing and Health Professions, 2009)
2. Vesicants (also referred to as blistering agents): A drug or agent capable
of causing tissue necrosis when extravasated (Mosbys, 2009)
3. Flare reaction: Erythema, pruritus, and localized urticaria at or adjacent
to the site of drug administration (Castells & Matulonis, 2012)
4. Irritant: An agent that produces inflammation or irritation (Mosbys, 2009)
B. Extravasation
1. Pathophysiology: Tissue damage secondary to vesicant infiltration or
leakage outside of the vessel that occurs as a result of one of two major
mechanisms
a) The vesicant binds to nucleic acids in the DNA of healthy cells in
the tissue, causing cell death. The dead cells release complexes,
which are taken up by adjacent healthy cells. This process of cellular uptake of extracellular substances sets up a continuing cycle of
tissue damage as the DNA-binding vesicant is retained and recirculated in the tissue for a long period of time (Luedke, Kennedy, &
Rietschel, 1979). Examples of DNA-binding vesicants include anthracyclines (daunorubicin, doxorubicin, epirubicin, idarubicin),
dactinomycin, mechlorethamine (nitrogen mustard), mitomycin,
and mitoxantrone.
b) The vesicant does not bind to cellular DNA. The vesicant has an indirect rather than direct effect on the cells in healthy tissue. It is eventually metabolized in the tissue and is more easily neutralized than
DNA-binding vesicants (Ener, Meglathery, & Styler, 2004). Examples
of non-DNA-binding vesicants include plant alkaloids (vinblastine,
vincristine, vindesine, vinorelbine) and taxanes (docetaxel, paclitaxel, paclitaxel protein-bound particles for injectable suspension),
which are mild vesicants.
2. Factors affecting tissue damage severity
a) Type of vesicant extravasated (DNA-binding or nonbinding)
b) Concentration and amount of vesicant in the tissue
c) Location of extravasation
d) Patient factors, such as older age, comorbidity (e.g., diabetes), and
impaired immunocompetence (Ener et al., 2004; Schulmeister, 2011)
3. Risk factors for peripheral extravasation (Goolsby & Lombardo, 2006;
Sauerland, Engelking, Wickham, & Corbi, 2006)
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4.

5.

6.

7.

a) Small, fragile veins


b) Previous multiple venipunctures
c) Prior treatment with irritating or sclerosing drugs, such as chemotherapy
d) Sensory deficits
e) Limited vein selection because of lymph node dissection, lymphedema, or limb removal
f) Impaired cognition, altered mental status (impairs ability to detect
administration site sensation changes), or somnolence
g) Probing during IV catheter insertion
h) Inadequately secured IV catheter
i) Administration site in areas with minimal overlying tissue (e.g., dorsum of the hand, wrist, or antecubital area)
j) Use of rigid IV devices (e.g., steel-winged butterfly needles)
Possible etiologies of peripheral extravasations (Sauerland et al., 2006)
a) Vein wall puncture, piercing, or trauma
b) Dislodgment of the catheter from the vein
c) Administration of a vesicant in a vein below a recent (less than 24
hours) venipuncture site
d) Administration of a vesicant in a vein below a recent or nonhealed
vesicant extravasation site
e) Inadvertent IM or SC vesicant administration
Risk factors for extravasation from central VADs (Sauerland et al., 2006)
a) Difficulty encountered during device insertion (e.g., probing during
venipuncture, inability to advance guidewire or catheter)
b) Inadvertent slicing, piercing, or nicking of catheter prior to or during insertion
c) Device misplacement with catheter tip outside of the venous system
d) Inadequately secured noncoring needles (implanted ports)
e) Deeply implanted ports
f) Presence of a fibrin sheath or thrombus at the catheter tip
g) Catheter migration
h) Long dwell time of catheters inserted using a subclavian approach (increases risk of catheter fracture secondary to compression or pinchoff between the clavicle and first rib)
Possible etiologies of extravasations from central VADs (Goossens, Stas,
Jrme, & Moons, 2011; Sauerland et al., 2006)
a) Vein perforation
b) Catheter leakage, rupture, or fracture
c) Separation of the catheter from a portal body (implanted ports)
d) Incomplete insertion of a noncoring needle into an implanted port
e) Noncoring needle dislodgment from an implanted port
f) Backflow of vesicant along the catheter to the venotomy site secondary to fibrin sheath or thrombus at the catheter tip
Signs and symptoms of vesicant extravasation: Irritation of the vein
and flare reactions may mimic some of the signs and symptoms of
vesicant extravasation (see Table 13 and Appendix 2). Irritation of
the vein and flare reactions are unique to peripheral chemotherapy administration; they do not occur when chemotherapy is administered via central VADs because the chemotherapy is rapidly diluted in large veins (Wickham, Engelking, Sauerland, & Corbi, 2006).
Signs and symptoms of vesicant extravasation are found in Table 13.
Additional signs and symptoms include the following (Ener et al.,
2004).
a) IV flow rate that slows or stops
b) Resistance during IV bolus (push) vesicant administration
c) Leaking around the IV catheter or implanted port needle
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Chapter 8. Infusion-Related Complications

157

Table 13. Signs and Symptoms Associated With Vesicant Extravasation, Venous Irritation, and Flare Reaction
Signs and
Symptoms

Vesicant Extravasation

Venous Irritation

Flare Reaction

Pain

Immediate: Pain typically occurs and is described


as burning, stinging, or a sensation of coolness at
and around the vesicant administration site. However, some patients do not experience pain when
a vesicant extravasates.
Delayed: Pain usually increases in intensity over
time.

Aching and tightness along a


peripheral vein, above the administration site, occurs as
the drug infuses.

No pain; the skin overlying the


vein may itch.

Redness

Immediate: Redness in the area of the vesicant administration site commonly occurs but is not always present or may be difficult to detect if the extravasation is occurring deeper in the tissue (e.g.,
as a result of needle dislodgment from implanted port).
Delayed: Redness generally intensifies over time.

The vein may appear reddened or darkened.

Immediate blotches or streaks


develop along the vein, which
usually subside within a few
minutes. Wheals may appear
along the vein.

Swelling

Immediate: Swelling commonly is observed and is


easier to detect when extravasation is superficial
(e.g., from a peripheral vein) rather than deep in
the tissue (e.g., implanted ports).
Delayed: Swelling typically increases over time.

Swelling does not occur.

Swelling does not occur.

Blood return

Immediate: Loss of blood return from IV device occurs.

Blood return should be present. If loss of blood return occurs, suspect infiltration of irritant.

Blood return is present.

Ulceration

Immediate: Skin integrity is intact


Delayed: If vesicant extravasation is not treated,
blistering and sloughing begin within 12 weeks,
followed by tissue necrosis that may require surgical debridement and skin grafting or flap placement.

Ulceration does not occur.

Ulceration does not occur.

Note. Based on information from Goolsby & Lombardo, 2006; Sauerland et al., 2006; Schulmeister, 2011.

8. Possible consequences of untreated vesicant extravasation (Ener et al.,


2004; Goolsby & Lombardo, 2006)
a) Blistering (usually begins within three to five days)
b) Peeling and sloughing of skin (usually begins within two weeks after extravasation)
c) Tissue necrosis (usually evident two to three weeks after extravasation)
(1) DNA-binding vesicants remain in the tissue for long periods of
time. The area of tissue necrosis becomes progressively larger
and deeper over time.
(2) Non-DNA-binding vesicants are more easily metabolized in the tissue. Tissue necrosis is generally localized and improves over time.
d) Damage to tendons, nerves, and joints
e) Functional and sensory impairment of the affected area
f) Disfigurement
g) Loss of limb
9. Vesicant extravasation management: A suspected vesicant extravasation
is best assessed and managed using a systematic and collaborative approach that involves the patient, the nurse administering the vesicant,
and the oncologist treating the patient.
a) Initial management of extravasation: Steps to take when a vesicant
extravasation occurs or is suspected (Goolsby & Lombardo, 2006;
Schulmeister, 2011)
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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(1) Immediately STOP administering the vesicant and IV fluids.


(2) Disconnect the IV tubing from the IV device. Do not remove
the IV device or noncoring port needle.
(3) Attempt to aspirate residual vesicant from the IV device or port
needle using a small (13 ml) syringe.
(4) Remove the peripheral IV device or port needle.
(5) Assess the site of the suspected extravasation.
(6) Assess symptoms experienced by the patient (e.g., pain, impairment in range of motion of extremity).
(7) Notify the physician or advanced practice nurse.
(8) Initiate appropriate management measures in accordance with
Table 14 and institutional policies.
b) Vesicant extravasation antidotes and treatments
(1) Efficacy: The efficacy of extravasation antidotes and treatments
is unknown, with the exception of dexrazoxane for injection,
which has a 98.2% overall efficacy for treating anthracycline
extravasation (Mouridsen et al., 2006). In two European studies, 53 of 54 patients with biopsy-confirmed anthracycline extravasation did not require surgical intervention after receiving
dexrazoxane administered IV daily for three days. The median
baseline extravasation area was 25 cm2 (range 1253 cm2), and
11 patients had extravasation areas exceeding 75 cm2. Thirteen
patients had late sequelae at the extravasation site such as pain,
Table 14. Vesicant Extravasation Management Guidelines
Classification/Drug

Immediate
Topical Therapy

Antidote or Treatment Administration,


Patient Monitoring, and Follow-Up

Antidote or Treatment

Alkylating agent
Mechlorethamine
hydrochloride
(nitrogen mustard,
Mustargen)

Apply ice for


612 hours following sodium
thiosulfate antidote injection
(Lundbeck,
2012).

Antidote: Sodium thiosulfate


Mechanism of action: Neutralizes mechlorethamine to form nontoxic thioesters that
are excreted in the urine
Preparation: Prepare 1/6 molar solution.
If 10% sodium thiosulfate solution: Mix 4
ml with 6 ml sterile water for injection.
If 25% sodium thiosulfate solution: Mix
1.6 ml with 8.4 ml sterile water.
Storage: Store at room temperature between 15C30C (59F86F).

Inject 2 ml of the sodium thiosulfate solution for each milligram of mechlorethamine suspected to have extravasated. Inject the solution SC into the extravasation site using a 25-gauge or smaller needle (change needle with each injection).
Assess the extravasation area for pain,
blister formation, and skin sloughing periodically as needed or in accordance with
institutional policy.
Instruct the patient to monitor the extravasation site and report fever, chills, blistering, skin sloughing, and worsening pain.
Instruct the patient with peripheral extravasations to report arm or hand swelling
and stiffness.

Anthracenedione
Mitoxantrone
(Novantrone)

Apply ice pack


for 1520 minutes at least
four times a
day for the first
24 hours.

No known antidotes or treatments

Extravasation typically causes blue discoloration of the infusion site area and may
require debridement and skin grafting
(EMD Serono, Inc., 2008).
Assess the extravasation area for pain,
blister formation, and skin sloughing periodically as needed or in accordance with
institutional policy.
In collaboration with the physician or advanced practice nurse, refer the patient
for specialized care when indicated or
needed (e.g., plastic or hand surgery
consult, physical therapy, pain management, rehabilitation services).
(Continued on next page)
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Chapter 8. Infusion-Related Complications

159

Table 14. Vesicant Extravasation Management Guidelines (Continued)


Classification/Drug

Immediate
Topical Therapy

Antidote or Treatment

Antidote or Treatment Administration,


Patient Monitoring, and Follow-Up

Anthracyclines
Daunorubicin
(Cerubidine)
Doxorubicin
(Adriamycin)
Epirubicin
(Ellence)
Idarubicin
(Idamycin)

Apply ice pack


(but remove at
least 15 minutes prior to
dexrazoxane
treatment).

Treatment: Dexrazoxane for injection (Totect Kit, Biocodex, Inc., 2011)


Note: Totect is the U.S. Food and Drug Administration (FDA)-approved treatment
for anthracycline extravasation, and its
manufacturer maintains a patent for use
on the product. Although Zinecard and
generic dexrazoxane are neither indicated nor FDA-approved for anthracycline
extravasation treatment, their clinical efficacy in treating anthracycline extravasations has been documented in the literature (Arroyo et al., 2010; CondeEstvez et al., 2010; Langer, 2007, 2008;
Uges et al., 2006).
Mechanism of action: Unknown
Dose: The recommended dose of dexrazoxane is based on the patients body surface area:
Day 1: 1,000 mg/m2
Day 2: 1,000 mg/m2
Day 3: 500 mg/m2
The maximum recommended dose is 2,000
mg on days 1 and 2 and 1,000 mg on day
3. The dose should be reduced 50% in patients with creatinine clearance values <
40 ml/min.
Preparation: Each 500 mg vial of dexrazoxane must be mixed with 50 ml diluent. The
patients dose is then added to a 1,000
ml normal saline infusion bag for administration.
Storage: Store at room temperature between 15C30C (59F86F).

The first dexrazoxane infusion should be


initiated as soon as possible and within 6
hours of the anthracycline extravasation.
Dexrazoxane should be infused over 12
hours in a large vein in an area other
than the extravasation area (e.g., opposite arm). The same arm should be
used only when the patients clinical status (e.g., lymphedema, loss of limb) precludes use of the unaffected arm, and a
large vein distal to the extravasation site
should be used for dexrazoxane administration.
Dimethyl sulfoxide should not be applied to
the extravasation area.
Assess the extravasation area for pain,
blister formation, and skin sloughing periodically as needed or in accordance with
institutional policy.
Instruct the patient to monitor the extravasation site and report fever, chills, blistering, skin sloughing, and worsening pain.
Instruct patients with peripheral extravasations to report arm or hand swelling and
stiffness.
Instruct the patient about treatment side
effects (e.g., nausea/vomiting, diarrhea,
stomatitis, bone marrow suppression, elevated liver enzyme levels, infusion-site
burning).
Monitor the patients complete blood count
and liver enzyme levels.

Antitumor antibiotics
Mitomycin
(Mutamycin)
Dactinomycin
(actinomycin D,
Cosmegen)

Apply ice pack


for 1520 minutes at least
four times a
day for the first
24 hours.

No known antidotes or treatments

Assess the extravasation area for pain,


blister formation, and skin sloughing periodically as needed or in accordance with
institutional policy.
In collaboration with the physician or advanced practice nurse, refer the patient
for specialized care when indicated or
needed (e.g., plastic or hand surgery
consult, physical therapy, pain management, rehabilitation services).

Plant alkaloids and


microtubule inhibitors
Vinblastine
(Velban)
Vincristine
(Oncovin)
Vinorelbine
(Navelbine)

Apply warm
pack for 15
20 minutes at
least 4 times
per day for
the first 2448
hours.
Elevate extremity (peripheral extravasations).

Antidote: Hyaluronidase
Mechanism of action: Degrades hyaluronic acid and promotes drug dispersion and
absorption
Preparation: Available hyaluronidase preparations are
Amphadase (bovine, hyaluronidase injection) (Amphastar Pharmaceuticals,
2005): Vial contains 150 units per 1 ml;
use 1 ml of solution. Do not dilute. Use
solution as provided. Store in refrigerator
at 2C8C (36F46F).

Administer 150 units of the hyaluronidase solution as five separate injections,


each containing 0.2 ml of hyaluronidase,
SC into the extravasation site using a
25-gauge or smaller needle (change
needle with each injection).
Assess the extravasation area for pain,
blister formation, and skin sloughing periodically as needed or in accordance with
institutional policy.
Instruct the patient to monitor the extravasation site and report fever, chills, blistering, skin sloughing, and worsening pain.

(Continued on next page)

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Table 14. Vesicant Extravasation Management Guidelines (Continued)


Classification/Drug

Immediate
Topical Therapy

Plant alkaloids and


microtubule inhibitors (cont.)

Taxanes
Docetaxel
(Taxotere)
Paclitaxel
(Taxol)
Paclitaxel proteinbound particles
for injectable
suspension
(Abraxane)

Apply ice pack


for 1520 minutes at least
4 times a day
for the first 24
hours.

Antidote or Treatment Administration,


Patient Monitoring, and Follow-Up

Antidote or Treatment
Hylenex (recombinant, hyaluronidase
human injection) (Halozyme Therapeutics, Inc., 2012): Vial contains 150 units
per 1 ml. Do not dilute. Use solution as
provided. Store in refrigerator at 2C8C
(36F46F).

Instruct patients with peripheral extravasations to report arm or hand swelling and
stiffness.

No known antidote or treatment

Docetaxel extravasation may cause hyperpigmentation, redness, and tenderness


(sanofi-aventis U.S. LLC, 2007).
Paclitaxel is a mild vesicant; extravasation may cause induration, blistering,
and rarely tissue necrosis (Bristol-Myers
Squibb Co., 2011; Stanford & Hardwicke,
2003).
Protein-bound paclitaxel extravasation
has been identified during post-approval use and reported to the manufacturer. It is advisable to monitor the infusion site closely for possible infiltration
during administration (Celgene Corp.,
2012).
Assess the extravasation area for pain,
blister formation, and skin sloughing periodically as needed or in accordance with
institutional policy.
Instruct the patient to monitor the extravasation site and to report fever, chills,
blistering, skin sloughing, and worsening pain.
Instruct patients with peripheral extravasations to report arm or hand swelling and
stiffness.

fibrosis, atrophy, and local sensory disturbance; all were judged


as mild (Mouridsen et al., 2006).
(2) Anecdotal reports: No clinical trials have been conducted to determine the efficacy of dimethyl sulfoxide, sodium thiosulfate,
hyaluronidase, growth factors, early surgical intervention, saline
washout or flush-out, or hyperbaric oxygen in treating biopsy-confirmed vesicant extravasations. Information about these antidotes
and treatments is anecdotal and based on case reports (Dougherty & Oakley, 2011; Goolsby & Lombardo, 2006; Schrijvers,
2003; Wickham et al., 2006).
10. Documentation of vesicant extravasation and treatment: Key elements
that may be included in vesicant extravasation documentation are listed in Figure 18. Extravasation treatments/antidotes used should also
be documented.
11. Patient follow-up: Dependent upon individual patient needs and institutional policies
a) Periodically assess the patients response to extravasation treatment.
b) Assessment may include inspection and measurement of the extravasation area, skin integrity, presence of pain or other symptoms, arm/
hand mobility (for peripheral extravasations), and sensation.
c) Obtain follow-up photographs that include the date and time in the
photograph per institutional policy.
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Chapter 8. Infusion-Related Complications

d) In collaboration with the physician or advanced practice nurse, refer the patient for specialized care when indicated (e.g., plastic or
hand surgery consultation, physical therapy, pain management, rehabilitation services).
e) Instruct the patient to protect the extravasation area from sunlight,
monitor the site, and report fever, chills, blistering, skin sloughing,
and worsening pain.
C. Irritation
1. Irritants: Chemotherapy agents that may inflame and irritate the peripheral veins include bleomycin, carboplatin, carmustine, dacarbazine, etoposide, floxuridine, gemcitabine, ifosfamide, liposomal daunorubicin,
liposomal doxorubicin, streptozocin, and topotecan (Ener et al., 2004;
Sauerland et al., 2006).
2. Irritants with vesicant properties
a) Oxaliplatin (Eloxatin)
(1) Has been described as both an irritant (de Lemos & Walisser, 2005; Kennedy, Donahue, Hoang, & Boland, 2003) and
a vesicant (Baur, Kienzer, Rath, & Dittrich, 2000). Case reports describe induration, edema, red-brown skin discoloration, hyperpigmentation, and rare instances of tissue necrosis. Kretzschmar et al. (2003) retrospectively reviewed 11 cases of peripheral oxaliplatin extravasation and found that even
with large-volume ( 40 mg) extravasations of oxaliplatin, tissue necrosis did not occur.
(2) Pericay et al. (2009) published a case report of a 165 mg dose
of oxaliplatin that extravasated when a noncoring needle dislodged from an implanted port, resulting in edema and skin
discoloration. They concluded that the effect was that of an irritant rather than a vesicant.
(3) The manufacturer of oxaliplatin states that extravasation
has, in some cases, included necrosis and injection-site reactions such as redness, swelling, and pain (sanofi-aventis
U.S. LLC, 2011).
(4) Because cold packs cause local vasoconstriction, they may precipitate or worsen the cold neuropathy associated with oxaliplatin.

Figure 18. Key Elements of Vesicant Extravasation Documentation


Date and time that extravasation occurred or was suspected
Type and size of peripheral venous access device or type of central venous access device
and gauge/length of noncoring needle (implanted ports)
Location and patency of peripheral or central venous access device
Number and location(s) of venipuncture attempts (for peripheral vesicant administration)
Description and quality of a blood return before and during vesicant administration
Vesicant administration technique (e.g., bolus, infusion)
Concentration and estimated amount of extravasated vesicant
Symptoms reported by patient (e.g., burning, pain)
Description of administration site appearance including measurement of edema and/or redness if present
Photographs of administration site that include date and time in the photograph field
Assessment of extremity (if applicable) for range of motion and discomfort with movement
Immediate nursing interventions (e.g., topical cooling or heating, physician notification)
Follow-up recommendations (e.g., referral to plastic surgery, return appointments)
Patient teaching (e.g., skin assessment, temperature monitoring, reporting pain)
Note. From Extravasation Management: Clinical Update, by L. Schulmeister, 2011, Seminars in Oncology
Nursing, 27, p. 85. doi:10.1016/j.soncn.2010.11.010. Copyright 2011 by Elsevier Inc. Reprinted with permission.

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(5) A warm pack applied to an oxaliplatin extravasation site is


preferable and may reduce local pain and inflammation (Foo,
Michael, Toner, & Zalcberg, 2003).
(6) High-dose dexamethasone (8 mg twice daily for up to 14 days)
has been reported to reduce oxaliplatin extravasation-related
inflammation (Kretzschmar et al., 2003).
b) Vinorelbine (Navelbine)
(1) Has been described as both an irritant (de Lemos, 2005;
Rittenberg, Gralla, & Rehmeyer, 1995) and a vesicant (Ener
et al., 2004; Goolsby & Lombardo, 2006; Hadaway, 2007; Sauerland et al., 2006). Case reports describe skin discoloration,
chemical phlebitis, localized rash, urticaria, blistering, and rarely, skin sloughing.
(2) The manufacturer of vinorelbine states that it is an irritant, and
extravasation may cause local tissue necrosis or thrombophlebitis (Bedford Laboratories, 2005).
(3) Data suggest that rapid IV infusion over 610 minutes followed
by a flush of more than 75124 ml of IV fluid may reduce vinorelbine-induced irritation (de Lemos, 2005).
c) Melphalan (Alkeran)
(1) Information in the literature is conflicting about the risk of extravasation injury associated with melphalan. The drug is listed as neither an irritant nor a vesicant by Dorr, Alberts, and Soble (1986),
as a possible irritant by Schwartz, Rockey, Surati, and Gullatte
(in press), as an irritant by Ener et al. (2004) and Goolsby and
Lombardo (2006), and as a vesicant by Sauerland et al. (2006).
(2) The manufacturer of IV melphalan states that care should be
taken to avoid possible extravasation, and in cases of poor peripheral venous access, use of a central venous line should be
considered (GlaxoSmithKline, 2010).
d) Bendamustine hydrochloride (Treanda): The manufacturer of
bendamustine states that it has received postmarketing reports of
bendamustine extravasation requiring hospitalization for erythema, marked swelling, and pain, and that precautions should be
taken to avoid extravasation (Cephalon, Inc., 2010). Dilution in
500 ml normal saline, which is recommended by the manufacturer, and an infusion time of one to two hours reduced bendamustine-induced venous irritation in a study of 21 patients in Japan
(Watanabe et al., 2013).
e) Irinotecan (Camptosar): The manufacturer of irinotecan states that
care should be taken to avoid extravasation of irinotecan, and should
extravasation occur, topical flushing of the skin with sterile water and
application of ice are recommended (Pfizer Inc., 2010).
3. Risk factors for irritation
a) Small veins
b) Prior treatment with irritating or sclerosing drugs, such as chemotherapy
4. Possible etiologies of venous irritation (Doellman et al., 2009)
a) pH (< 5 or > 9) of infused drugs
b) Hypertonic solutions (e.g., osmolarity > 350 mOsm/L)
c) Concentrated drugs or infusion solutions
5. Signs and symptoms of venous irritation: See Table 13.
6. Management of venous irritation
a) Application of warm pack may reduce local discomfort.
b) Restarting the peripheral IV in a larger vein in another location may
be indicated.
c) Consult a pharmacist to explore diluting irritating medications.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 8. Infusion-Related Complications

d) Instruct patients to report the development of a hard cord along the


vein, pain, and temperature elevation.
D. Flare reaction: A flare reaction occurs during peripheral administration of
doxorubicin and is thought to be due to local release of histamine from mast
cells or basophils (Curran, Luce, & Page, 1990). It is characterized by transient erythema along the vein proximal to the IV site and may be accompanied by pruritus and urticaria. Flare reactions are distinguishable from extravasation by the lack of pain or swelling and the presence of blood return
(Castells & Matulonis, 2012). In the event of a flare reaction,
1. Verify presence of blood return. If absent, assess for signs and symptoms
of extravasation.
2. Flush the vein slowly with saline and observe for resolution of flare, usually within 45 minutes.
3. If resolution does not occur, obtain an order from an authorized prescriber to administer hydrocortisone or diphenhydramine. For adults,
the diphenhydramine dose is 2550 mg IV followed by a saline flush.
4. Do not resume the infusion through the IV site until the flare reaction
resolves completely. Consider restarting the IV in another site.
5. If the drug is administered again at a later date, premedication with an
antihistamine and/or corticosteroids may prevent flare reaction (Castells & Matulonis, 2012).
6. Document the episode, including all treatment(s) and the patients response, according to institutional policy.
E. Acute infusion reactions: Hypersensitivity, anaphylaxis, and cytokine-release
syndrome
1. Pathophysiology
a) Hypersensitivity and anaphylaxis are mediated by the immune system
and usually are allergic in nature. These reactions may be triggered
by an allergen to which the patient is sensitized. The allergen may be
a chemotherapy or biotherapy agent, its metabolites, or the drug diluent (Lee, Gianos, & Klaustermeyer, 2009). The agents cause direct
or immunoglobulin E (IgE)-mediated mast cell degranulation with
release of histamine. Some reactions may be related to complement
activation. Symptoms range from itching at the injection site to systemic shock caused by smooth muscle contraction, increased vascular
permeability, and vasodilation (Soar, 2009). Reactions usually occur
within 530 minutes of initiating the dose of chemotherapy but may
occur hours later with some agents (Gobel, 2005; Lee et al., 2009).
b) Cytokine-release syndrome, which is commonly referred to as infusion
reaction, is a symptom complex that occurs in association with mAb
infusions. This type of reaction is related to the release of cytokines
such as IL-2, IFN, and TNF from the targeted cells and other recruited immune cells, such as lymphocytes (Breslin, 2007).
2. Risk factors for hypersensitivity and anaphylaxis (Gobel, 2005)
a) Administration of a chemotherapy agent known to cause hypersensitivity reactions (see Figure 19)
b) Preexisting allergies, such as to foods, drugs, bee stings (Grosen, Siitari, Larrison, Tiggelaar, & Roecker, 2000), blood products, or radiographic contrast media
c) Previous exposure to the agent
d) Failure to administer known effective prophylactic premedications
3. Risk factors for cytokine-release syndrome: See Figure 20 (Breslin, 2007;
Gobel, 2007; Lenz, 2007).
a) First infusion of mAbs
b) Chemotherapy-nave patients receiving mAbs
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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Figure 19. Immediate Hypersensitivity Reactions:


Predicted Risk of Chemotherapy
High Potential
L-Asparaginase
Taxanes
Paclitaxel
Docetaxel
Platinum compounds
Cisplatin
Carboplatin
Oxaliplatin
Epipodophyllotoxins
Etoposide
Teniposide

Occasional Potential
Anthracyclines
Doxorubicin
Daunorubicin
Idarubicin
Epirubicin
Mercaptopurine
Azathioprine

Rare Potential
Bleomycin
Chlorambucil and melphalan
Cyclophosphamide and
ifosfamide
Cytarabine and fludarabine
Dacarbazine
Dactinomycin
5-Fluorouracil
Hydroxyurea
Methotrexate
Polyethylene glycol-modified E. coli asparaginase
Vincristine and vinblastine

Note. From Chemotherapy-Induced Hypersensitivity Reactions, by B.H. Gobel, 2005, Oncology Nursing Forum, 32, p. 1028. doi:10.1188/05.ONF.1027-1035. Copyright 2005 by Oncology Nursing Society. Reprinted
with permission.

Figure 20. Biotherapy Drugs Associated With Hypersensitivity Reactions


and Cytokine-Release Syndromes
Interferon
Interferon alfa
Interferon beta (1A and 1B)
Interferon gamma
Interleukin
Aldesleukin
Denileukin diftitox
Kinase Inhibitor
Temsirolimus

Monoclonal Antibodies
Murine
Ibritumomab tiuxetan
Tositumomab
Chimeric
Brentuximab
Cetuximab
Rituximab
Humanized
Alemtuzumab
Bevacizumab
Gemtuzumab ozogamicin
Trastuzumab
Fully human
Ipilimumab
Ofatumumab
Panitumumab

Note. Based on information from Bristol-Myers Squibb Co., 2013; GlaxoSmithKline, 2011; Gobel, 2007;
Lenz, 2007; Seattle Genetics, Inc., 2012; Wyeth Pharmaceuticals, 2012.

c) Patients with leukemia or lymphoma, especially those having high


circulating lymphocyte counts (> 25,000/mm3)
4. Preadministration guidelines: Implement the following steps to prevent
and manage hypersensitivity reactions, anaphylaxis, and infusion reactions.
a) Obtain and record baseline vital signs.
b) Review the patients allergy history (e.g., food, medication, environment).
c) Administer premedications as ordered. Common premedications include histamine (H) blockers (e.g., H1 blocker [diphenhydramine], H2
blocker [ranitidine], acetaminophen (for mAbs), and dexamethasone.
d) Ensure emergency equipment and medications are readily available.
e) Obtain physician orders for emergency treatment before drug administration. Written standing orders for management of hypersensitivity and infusion reactions are recommended (Gobel, 2005; Lenz,
2007; Viale, 2009).
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 8. Infusion-Related Complications

f) Instruct the patient to report symptoms of hypersensitivity and infusion reaction.


g) Monitor for reactions with each treatment; hypersensitivity reactions
can occur with a patients repeated exposure to a drug and at any
time during the infusion or the treatment cycle. For example, the incidence of hypersensitivity reactions with platinum-containing agents
increases with multiple doses and can occur after the drug has been
infused (Gobel, 2005; Lee et al., 2009; Winkeljohn & Polovich, 2006).
h) Perform an intradermal skin test or administer a test dose before
the initial dose of the drug to a patient who has a high likelihood
of a hypersensitivity reaction. For a patient receiving repeated doses
of carboplatin, a valid method of predicting a reaction is a skin test
performed after the sixth dose. False-positive and false-negative skin
tests are possible with oxaliplatin and asparaginase (Lee et al., 2009).
(1) Observe the patient for any local or systemic reaction for a minimum of 30 minutes. If no sign of reaction is evident, proceed
with the initial dosing.
(2) When administering an IV drug that is associated with hypersensitivity, observe the patient for signs and symptoms of reaction and be prepared to intervene.
(a) Any patient who has had a severe anaphylactic reaction accompanied by hypotension should not be treated again with
that agent except in special circumstances (Viale, 2009).
(b) Avoid administering subsequent doses if a patient is considered to be sensitized to the drug. If the drug is critical
to the treatment plan, premedication with antihistamines
or corticosteroids (Gobel, 2005; Lenz, 2007) or a desensitization protocol (Cortijo-Cascajares et al., 2013; Lee et
al., 2009; Viale, 2009) may prevent a recurrent hypersensitivity reaction. Discontinuation and drug substitution may
be necessary.
5. Clinical manifestations of anaphylaxis (Soar, 2009) and hypersensitivity
a) Airway compromise, such as tongue or throat swelling, stridor, hoarseness
b) Breathing difficulties, such as shortness of breath, wheezing, cyanosis, or respiratory arrest
c) Circulatory compromise, such as tachycardia, hypotension, myocardial ischemia, or cardiac arrest
d) Neurologic changes, such as confusion, agitation, or loss of consciousness
e) Skin and mucosal changes, such as erythema, urticaria, or periorbital or facial edema
f) Abdominal cramping, diarrhea, nausea, and vomiting (less common)
6. Clinical manifestations of cytokine-release syndrome (severe reactions are
characterized by rapid onset and more severe symptoms) (Breslin, 2007)
a) Fever or chills
b) Nausea
c) Hypotension
d) Tachycardia
e) Asthenia
f) Headache
g) Rash
h) Tongue and throat swelling
i) Dyspnea
7. Emergency management of anaphylaxis: Symptoms of reaction usually
arise within 30 minutes of initial administration or increase in infusion
rate (Gobel, 2005). Immediate action is imperative.
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a) STOP drug infusion immediately.


b) Maintain an IV line with normal saline or another appropriate solution.
c) Stay with the patient. Have another staff member notify the physician
and emergency team, or, if outside the hospital setting, call the local
emergency medical service.
d) Place the patient in a comfortable position: sitting if short of breath
or vomiting, lying flat if hypotensive with elevated legs for shock (systolic blood pressure < 60 mm Hg).
e) Monitor vital signs (pulse, respirations, blood pressure, oxygen saturation) every 2 minutes until the patient is stable, then every 5 minutes for 30 minutes, then every 15 minutes. Monitor electrocardiogram (ECG) for serious reactions.
f) Maintain airway, assessing the patient for increasing edema of the respiratory tract. Administer oxygen if needed. Anticipate the need for
cardiopulmonary resuscitation.
g) Administer emergency medications based on symptoms (Sampson et
al., 2006; Soar, 2009) (see Table 15).
h) Provide emotional support to the patient and family.
i) Document all treatments and the patients response in the medical
record.

Table 15. Emergency Drugs for Use in Case of Hypersensitivity or Anaphylactic Reactions*
Indication

Drug

Dose

Comments

Bronchial constriction
(dyspnea, wheezing,
stridor)

Epinephrine

0.10.5 mg IM into thigh (0.10.5


ml of 1:1,000 solution or EpiPen
0.3 mg automatic device)

IM administration is preferred over IV to minimize adverse cardiac effects. Anterior-lateral


thigh is preferable to deltoid (may also be administered by inhalation or subcutaneously).
May repeat every 510 minutes if needed.

Shortness of breath,
tachypnea (rate > 20
breaths per minute), or
decreased oxygen saturation

Oxygen

610 L/min by face mask

Patients who are hemodynamically unstable


may also benefit from oxygen.

Albuterol

2.5 mg by inhalation (3 ml of
0.083% inhalation solution) by nebulizer

Hold if heart rate is > 110 beats per minute.

Hypotension (> 30%


decrease in systolic
blood pressure from
baseline)

Epinephrine

0.10.5 mg IM into thigh (0.10.5


ml of 1:1,000 solution or EpiPen
0.3 mg automatic device) or 50
100 mcg IV bolus (0.2 mcg/kg) for
hypotension (0.51 ml of 1:10,000
solution)

IM administration is preferred over IV to minimize adverse cardiac effects, except in the


presence of cardiovascular collapse. Cardiac
monitoring is recommended.

Normal saline IV

500 ml fluid bolus

Over 10 minutes 1, then as ordered. Multiple fluid boluses may be required if patient
remains hypotensive despite epinephrine.

Diphenhydramine

2550 mg IVP

Famotidine
OR

20 mg IV

To counteract the multiple effects of histamine release, both H1 and H2 blockers should
be administered.

Ranitidine

50 mg IV

Methylprednisolone

3050 mg IV

Hydrocortisone
injection

100500 mg IV

Dexamethasone

1020 mg IV

Hives, itching, flushing,


swollen lips or tongue

To prevent delayed
reaction

Limited evidence is available to support this


recommendation, although steroids have
been used frequently.

* Additional emergency medications (e.g., sodium bicarbonate, furosemide, lidocaine, naloxone hydrochloride, sublingual nitroglycerine) and emergency
supplies (e.g., oxygen, suction machine with catheters, Ambu bag) should be available in case of medical emergency.
IMintramuscular; IVintravenous; IVPintravenous push
Note. Based on information from Sampson et al., 2006; Soar, 2009.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 8. Infusion-Related Complications

167

j) Symptoms of anaphylaxis may recur hours after initial intervention; therefore, patients who have experienced a grade 3 or 4 reaction (NCI CTEP, 2010) should be hospitalized and monitored
closely for 24 hours (Sampson et al., 2006). See Table 16 for grading criteria.
8. Clinical management of cytokine-release syndrome (Gobel, 2007; Lenz,
2007)
a) Stop infusion, and observe the patient until symptoms resolve, which
usually occurs within 30 minutes.
b) Administer additional H blockers as ordered.
c) Resume infusion at a slower rate (50%) after resolution of symptoms,
and titrate the rate slowly.
d) For severe reactions (Table 16), administer emergency medications
based on symptoms (see Table 15).
9. Clinical management of localized hypersensitivity (Wilkes, 2010)
a) Observe for and evaluate symptoms (e.g., urticaria).
b) Administer diphenhydramine, ranitidine, or corticosteroids per physician order or according to protocol.
c) Monitor vital signs at least every 15 minutes for 1 hour or as the patients condition requires.
d) Document the episode, including all treatments and the patients response, according to institutional policies.
F. Patient and caregiver education
1. Before cytotoxic therapy, inform the patient and family that chemotherapy and biotherapy agents have the potential for early complications. Instruct them to immediately report signs and symptoms of extravasation,
flare, hypersensitivity, or infusion reactions.
Table 16. Grading Criteria for Allergic Reactions, Anaphylaxis, and Cytokine-Release Syndrome
Grade
Adverse Event

Allergic reaction

Transient
flushing or
rash, drug fever < 38C (<
100.4F); intervention not indicated

Intervention or infusion interruption indicated; responds promptly to


symptomatic treatment
(e.g., antihistamines,
NSAIDs, narcotics); prophylactic medications indicated for 24 hours

Prolonged (e.g., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms
following initial improvement; hospitalization indicated for clinical sequelae (e.g., renal impairment, pulmonary infiltrates)

Life-threatening
consequences; urgent intervention
indicated

Death

Symptomatic bronchospasm, with


or without urticaria; parenteral intervention indicated; allergy-related
edema/angioedema; hypotension

Life-threatening
consequences; urgent intervention
indicated

Death

Mild reaction;
infusion interruption not indicated; intervention not indicated

Therapy or infusion interruption indicated but


responds promptly to
symptomatic treatment
(e.g., antihistamines,
NSAIDs, narcotics, IV
fluids); prophylactic medications indicated for
24 hours

Prolonged (e.g., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms
following initial improvement; hospitalization indicated for clinical sequelae (e.g., renal impairment, pulmonary infiltrates)

Life-threatening
consequences;
pressor or ventilatory support indicated

Death

Anaphylaxis

Cytokinerelease
syndrome

IVintravenous; NSAIDsnonsteroidal anti-inflammatory drugs


Note. From Common Terminology Criteria for Adverse Events [v.4.03], by the National Cancer Institute Cancer Therapy Evaluation Program, 2010. Retrieved from http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf.

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

2. Document all patient teaching. Schulmeister and Camp-Sorrell (2000)


stated that plaintiffs in extravasation lawsuits typically deny being informed of the risk of extravasation or state that they were led to believe
that the risk was minuscule (p. 532).
3. After therapy, instruct the patient and family about the importance of
immediately reporting symptoms of any delayed reaction.

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Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9

Side Effects of Cancer


Therapy
A. Myelosuppression: Neutropenia, anemia, and thrombocytopenia
1. Myelosuppression is a condition manifested by a significant decrease in
the number of neutrophils, megakaryocytes, and erythrocytes within the
bone marrow (NCI, n.d.). Myelosuppression is a dose-limiting toxicity
of systemic chemotherapy (Camp-Sorrell, 2011). Terms used in this section include the following.
a) Neutropenia: A significant reduction in the absolute number of circulating neutrophils in the blood. The absolute neutrophil count (ANC)
is the basis for neutropenia classification and is generally defined as
an ANC < 1,500 neutrophils/microliter (mcl) (Watts, 2009). NCCN
(2013f) and the Infectious Diseases Society of America (Freifeld et
al., 2011) define neutropenia as < 500 neutrophils/mcl or < 1,000
neutrophils/mcl with the expectation that the neutrophil count will
decline to < 500 neutrophils/mcl over 48 hours. NCI CTEP (2010)
outlines the grading of neutropenia.
(1) Mild: ANC < lower limit of normal (LLN)1,500 neutrophils/mcl
(2) Moderate: ANC < 1,5001,000 neutrophils/mcl
(3) Severe: ANC < 1,000500 neutrophils/mcl
(4) Life-threatening: ANC < 500 neutrophils/mcl
b) Anemia: In adults, anemia is defined as a hemoglobin (Hgb) < 11 g/
dl or > 2 g/dl below baseline (NCCN, 2013c). Other references for
adults in industrialized nations identify 14 g/dl for men and 12 g/dl
for women as lower limits for normal Hgb. A decrease in the hematocrit (Hct) level or number of red blood cells (RBCs) can be used
to define anemia, but Hgb is the value used most often because it reflects physiologic consequences of anemia (Means & Glader, 2009).
NCI CTEP (2010) outlines the grading of anemia.
(1) Grade 1: 10 g/dl to < LLN
(2) Grade 2: 8.09.9 g/dl
(3) Grade 3: 6.57.9 g/dl
(4) Life-threatening: < 6.5 g/dl
c) Thrombocytopenia: Platelet count below the LLN, 400150 109/L
(Liles & Knupp, 2009). NCI CTEP (2010) outlines the grading of decreased platelet count.
(1) Mild: < LLN75,000/mcl
(2) Moderate: < 75,00050,000/mcl
(3) Severe: < 50,00025,000/mcl
(4) Life-threatening: < 25,000/mcl
d) Cytopenia: The lack of cellular elements in circulating blood
e) Pancytopenia: A depression of the normal bone marrow elements; white
cells, red cells, and platelets in the peripheral blood (Harmening, 2009)
f) Nadir: Following cytotoxic therapy, the time or level at which the
lowest blood cell count is reached (OLeary, 2010). The nadir varies
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with individual agents but usually occurs 710 days after treatment
(Camp-Sorrell, 2011).
g) Hematopoiesis
(1) The processes involved in the production of all blood cells
from hematopoietic stem cells (HSCs). In adults, most hematopoiesis occurs in the bone marrow in myeloid tissue (see
Figure 21).
(2) The process begins with HSCs, also called pluripotent stem cells
(Bell, Harmening & Hughes, 2009; Koury, Mahmud, & Rhodes,
2009). These are the most primitive type of blood cell and the
source of all hematopoietic cells. Pluripotent stem cells are able
to self-renew and maintain their numbers because they have the
capacity to proliferate, differentiate, and mature into all cell lines.
With each stem cell division, one daughter cell stays in the stem
cell pool while the other daughter cell leaves the stem cell pool
and becomes committed to a distinct cell line. These committed progenitor cells differentiate and mature in the bone marrow. Whether HSCs proliferate or differentiate is determined
by the bodys needs in response to exogenous (e.g., high altitude) or endogenous (e.g., stress, infection, hemorrhage, drug
therapy) influences. Once released into the bloodstream, mature cells have a varied life span (see Table 17).
2. Most chemotherapy agents cause some degree of myelosuppression. The
degree and duration of chemotherapy-related myelosuppression is related to the agents mechanism of action (e.g., cell cyclespecific drugs
are associated with rapid cytopenias).
3. Neutropenia: Chemotherapy-induced neutropenia (CIN) is the primary dose-limiting toxicity associated with systemic chemotherapy (Harmening, Marty, & Strauss, 2009). It has significant negative clinical consequences for patients with cancer, including life-threatening infections,
prolonged hospital stays, dose reductions, and dose delays.
a) Normal physiology of neutrophils (see Figure 21): Neutrophils and
monocytes stem from the colony-forming unitgranulocyte-macrophage progenitor cell. The earliest identifiable cell of the neutrophil
lineage is the myeloblast. Differentiation from a myeloblast to a segmented neutrophil takes 711 days. Normal adult bone marrow produces approximately 1 1011 neutrophils each day (Harmening, Marty, et al., 2009). The major steps of development follow (Bell et al.,
2009).
(1) The pluripotent stem cell gives rise to the myeloblast, the earliest form of the neutrophil. During this phase, the nucleus is
round. At the end of this phase, granules are evident as the cell
transitions to a promyelocyte.
(2) Promyelocytes have a large nucleus, averaging three to five
times larger than the cytoplasm of the cell. During this phase,
the granules begin to fade.
(3) During the myelocyte phase, primary granules decrease and secondary neutrophilic granules appear. Myelocytes may have nuclei that are round, oval, or flattened on one side.
(4) Metamyelocytes are observed with indented nuclei that make
them appear bean-shaped.
(5) Band neutrophils evolve when the indentation of the nucleus
is more than half the width of the nucleus. At this point, the
cell is approximately 24 hours from maturation into a segmented neutrophil. In the presence of acute infection or inflammation, bands are released early from the marrow and complete
maturation in circulation.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Figure 21. Hematopoiesis

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Table 17. Life Spans of Blood Components


Blood Component

Typical Life Span

Red blood cell

90120 days

Platelet

810 days

Neutrophil

< 1 day to approximately 5.4 days

Monocyte

5 days, but dependent on many factors

Macrophage

Dependent on many factors

Eosinophil

818 hours in blood and 25 days in tissue

Basophil

12 days

Tissue mast cell

Cutaneous: 1 year; mucosal: 12 weeks

B lymphocyte

Depends on type and subtype

T lymphocyte

Depends on type and subtype

Natural killer cell

Approximately 10 days

Note. Based on information from Kitamura, 1989; Milot & Filep, 2011; Min et al., 2012; Nayak et al., 2013;
Park & Bochner, 2010; Pillay et al., 2010; Whitelaw, 1966; Zhang, Wallace, et al., 2007.

(6) In the segmented neutrophil phase, the nucleus has two to five
lobes connected to each other by fine strands.
b) Locations of neutrophils (Bell et al., 2009).
(1) The bone marrow of a healthy adult contains both mature segmented neutrophils and immature neutrophils in various stages of development. Neutrophils leave the bone marrow for the
blood through pores that form between the marrow parenchyma and venous blood vessels.
(2) Once in the bloodstream, these cells join the functional
pool by circulating or lining blood vessel walls as marginated cells, meaning they are adhering to endothelial cells lining the blood vessel. Neutrophils exist in the bloodstream
as mature and immature cells. These cells perform a critical
role in the bodys defense by generating chemotactic agents
(e.g., endotoxin-activated serum [Anderson, Glover, & Robinson, 1978]) in response to infection. The result is activation of neutrophil defense and movement of neutrophils to
the site of infection.
(3) Neutrophils leave the blood for tissue by migrating through endothelial cells, a process called diapedesis. After neutrophils enter
the tissue, they do not return to circulation or the bone marrow.
c) Pathophysiology
(1) The bone marrow must constantly produce neutrophils because
the life span of a neutrophil is estimated to be only 712 hours
(see Table 17). Chemotherapeutic agents suppress bone marrow activity and damage stem cells, preventing them from continuing the maturation process. Therefore, chemotherapy decreases the neutrophil count as mature neutrophils die and are
not replaced (Camp-Sorrell, 2011).
(2) The WBC nadir depends on the specific drugs and dosages
used. A prolonged nadir may occur if stem cells fail to repopulate quickly following high-dose chemotherapy (OLeary,
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Chapter 9. Side Effects of Cancer Therapy

2010). Neutropenia occurs 812 days following chemotherapy and resolves 2128 days after chemotherapy.
(a) Cell cyclespecific agents (e.g., antimetabolites) are generally less damaging because they primarily affect cells in
a specific phase of the cell cycle. Severe neutropenia can
develop when cell cyclespecific drugs are used in doseintensification and combination chemotherapy regimens
(Camp-Sorrell, 2011).
(b) Cell cyclenonspecific agents (e.g., alkylating agents, nitrosoureas) are damaging to cells in all phases of the cell
cycle, thereby causing more damage to stem cells. The extent of neutropenia with these agents is dependent on dose,
schedule, and agent. For example, oxaliplatin as a single
agent is expected to cause mild neutropenia, but in regimens with 5-FU and leucovorin, toxicity can be much higher (Camp-Sorrell, 2011).
(c) Some cell cyclenonspecific agents (e.g., nitrosoureas) produce a delayed and prolonged neutropenia.
i. In adults, nadir occurs at 2146 days, with recovery at
3560 days (Wilkes & Barton-Burke, 2012).
ii. In children, nadir with BCNU (carmustine) occurs
at 2135 days, with recovery at 4250 days (Hennessy
& Scott, 2008).
d) Risk factors for developing neutropenia: Risk assessment for CIN
should be done prior to each cycle of therapy, including initial therapy (see Figure 22) (NCCN, 2013d; OLeary, 2010).
e) Fever and febrile neutropenia: Fever is defined as a one-time oral
temperature > 101F (38.3C) or oral temperature of 100.4F

Figure 22. Risk Factors for Developing Febrile Neutropenia


Patient Related
Older than 65 years
Female
Poor performance status
Poor nutritional status
Low neutrophil count at the beginning of a treatment cycle
Renal dysfunction
Liver dysfunction, especially elevated bilirubin
Cardiovascular disease
Recent surgery
Preexisting infection
Open wounds
Disease Related
Advanced disease stage
Tumor involvement of the bone marrow
Type of malignancy: hematologic (leukemia, myelodysplastic syndromes), breast, lung,
colorectal, ovarian, and lymphoma
Preexisting, prolonged, or previous episode of neutropenia
Treatment Related
Previous myelosuppressive chemotherapy or radiation
Treatment intent (curative intent rather than palliative)
Planned relative dose intensity ( 85%)
Use of specific medications (e.g., immunosuppressive drugs)
Chemotherapy intensity (i.e., dose dense, high dose, myeloablative)
Note. From Putting Evidence Into Practice: Improving Oncology Patient Outcomes; Prevention of Infection (p.
7), by M. Irwin, C. Erb, C. Williams, B.J. Wilson, and L.J. Zitella, 2013, Pittsburgh, PA: Oncology Nursing Society. Copyright 2013 by the Oncology Nursing Society. Reprinted with permission.

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(38C) lasting one hour. Febrile neutropenia occurs when the ANC
is < 500/mcl or < 1,000/mcl with anticipated decline to < 500/mcl
over the next 48 hours and fever as defined previously (NCCN,
2013f).
f) Risk assessment
(1) Assess for febrile neutropenia risk prior to each treatment cycle (Irwin, Erb, Williams, Wilson, & Zitella, 2013). Increased
infection risk is present in patients with fever in the presence
of neutropenia.
(2) Risk factors for developing febrile neutropenia (NCCN, 2013f)
(a) Advanced age
(b) Low neutrophil count at the beginning of chemotherapy cycle
(c) Tumor involvement of bone marrow
(d) Poor performance status
(e) Renal dysfunction
(f) Liver dysfunction, especially elevated bilirubin
(g) Previous myelosuppressive chemotherapy or radiation
(h) Preexisting infection, open wounds, or recent surgery
(i) Chemotherapy regimens (e.g., high-dose therapy, dosedense therapy)
(j) Use of specific medications including but not limited to
phenothiazines, diuretics, and immunosuppressive drugs
g) Clinical manifestation of infection in patients with neutropenia
(Camp-Sorrell, 2011; Freifeld et al., 2011; NCCN, 2013f; OLeary,
2010; Shelton, 2011)
(1) A fever > 100.4F (38C) is the most reliable, and often the
only, sign of infection in patients with neutropenia. Normally, WBCs cause the classic signs of infection (e.g., redness,
edema, pus). Extremely neutropenic patients, however, may
not be able to manifest the usual signs of infection (NCCN,
2013f).
(2) Common sites of infection and corresponding signs and symptoms in neutropenic patients
(a) GI tract: Fever, abdominal pain, alimentary mucositis (mucositis at any level of the digestive tract), diarrhea
(b) Respiratory tract: Fever, cough, dyspnea on exertion, adventitious breath sounds, chest discomfort, asymmetric chest
wall movement, nasal flaring
(c) Genitourinary tract: Fever, dysuria, frequency, urgency, hematuria, cloudy urine, flank pain, perineal itching, vaginal discharge
(d) Head and neck: Swelling, itching, redness or drainage of
eyes, pain or discharge of ears, nasal congestion or drainage, oral ulcerations, difficulty swallowing, fever
(e) Indwelling devices (e.g., VADs, ventricular peritoneal shunts): Fever, erythema, pain or tenderness, edema,
drainage, induration at site
(f) Dermatologic and mucous membranes: Erythema, tenderness, warm skin, edema (especially in axilla, mouth, sinuses
and perineal or rectal areas), rashes, itching, skin lesions,
fever, draining open wounds
(g) Central nervous system (CNS): Change in mental status,
headache, seizure, vision changes, photosensitivity, fever,
nausea, lethargy
(h) Hematologic/immunologic: Decrease in diastolic blood
pressure, headache, oliguria, fever, flushed appearance
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Chapter 9. Side Effects of Cancer Therapy

(3) Septic shock associated with neutropenia has a high mortality


rate (Vusirikala, 2009).
h) ANC calculation: Use laboratory data to assess neutropenia by calculating the ANC. Note that neutropenia can occur when the total WBC
count is within a normal range (4,00010,000/mcl) (Camp-Sorrell,
2011). Consequently, calculating the ANC is essential to achieving a
correct assessment of neutrophil status. To calculate ANC, ANC = %
(polys + bands) WBC.
(1) Obtain complete WBC count including differential. The differential will include mature neutrophils, also referred to as segs
for segmented neutrophils or PMNs/polys for polymorphonuclear neutrophils. In addition, less mature neutrophils will be
present; these are known as bands.
(2) Add the total number of mature polys and less mature neutrophil bands.
(3) Convert sum from (2) to a percentage.
(4) Multiply total WBC count by total neutrophil percentage (polys + bands). ANC calculation example: WBC = 1,500, polys =
30; bands = 5.
(a) Add polys and bands: 30 + 5 = 35.
(b) Convert sum to percentage: 35 100 = 0.35 = 35%.
(c) Multiply WBC count by percentage to find ANC: 1,500;
0.35 = 525/mcl.
i) Collaborative management
(1) Nurses play an important role in preventing infection in patients
with neutropenia and cancer through evidence-based nursing
practice, research, and patient education (Irwin et al., 2013).
(a) Hand hygiene: Proper hand hygiene is the most effective
measure to prevent the spread of infection. It reduces the
risk of healthcare-associated infections by decreasing person-to-person transmission of pathogens (CDC, 2012; Freifeld et al., 2011; Irwin et al., 2013).
(b) Diet: No recent studies have linked neutropenic diets (restricting fresh fruits and vegetables) with a lower risk of
infection for neutropenic patients with cancer. Dietary
precautions regarding the omission of fresh fruit and vegetables remain unsupported (Gardner et al., 2008). Uncooked fruits and vegetables should be thoroughly washed
(Freifeld et al., 2011; Irwin et al., 2013). Basic safe food
handling practices, such as avoiding uncooked and undercooked meats, seafood, and eggs and unwashed fruits
and vegetables, should be employed (Freifeld et al., 2011;
Wilson, 2002).
(c) Environment: Protective or strict isolation studies reveal
no significant differences in documented infections, febrile episodes, or antibiotic use for patients with CIN.
Protective isolation has no effect on the hosts endogenous flora and no impact on organisms transmitted by
water or food (Freifeld et al., 2011).
i. In general, patients with CIN do not require specific
room ventilation.
ii. Allogeneic hematopoietic stem cell transplantation
(HSCT) recipients are recommended to be placed in
rooms with HEPA filtration with > 12 air exchanges
per hour. Air pressure in these rooms should be positive when compared to surrounding areas, such as
hallways, toilets, and anterooms.
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(d) Plants and flowers: No research studies are available that


evaluate the potential harm of plants and flowers to patients with CIN (Irwin et al., 2013).
i. Because fresh or dried flowers could expose patients
with cancer to Aspergillus and Fusarium, they should be
kept out of patient rooms (Freifeld et al., 2011).
ii. If plants must be present, plant care should be done
by staff not directly caring for patients (Sehulster &
Chinn, 2003).
iii. If caregivers are unable to avoid plant care, they should
wear gloves and perform hand hygiene after removing gloves.
(e) Treatment with colony-stimulating factors (CSFs) (see Table 9)
i. Granulocyte macrophagecolony-stimulating factor
(GM-CSF) (sargramostim) (Genzyme Corp., 2009b)
ii. Granulocytecolony-stimulating factor (G-CSF) (filgrastim, pegfilgrastim [Amgen, 2012c, 2013a]). NCCN
(2013d) recommends use of these drugs when the risk
of febrile neutropenia is > 20%.
iii. The manufacturer recommends initiation of G-CSF
no earlier than 24 hours following chemotherapy.
iv. The manufacturer of G-CSF warns that safety of administration simultaneously with chemotherapy has
not been established. Rationale is the potential sensitivity of rapidly dividing myeloid cells to cytotoxic
agents (Amgen, 2012c, 2013a).
(f) Preventing trauma to the patients skin and mucous membranes (Freifeld et al., 2011; OLeary, 2010; Shelton,
2011)
i. Provide meticulous care for all indwelling devices.
ii. Prevent pressure sores and constipation.
iii. Change water in pitchers, denture cups, and nebulizers at least daily.
iv. Consider risk-benefit ratio for invasive procedures (e.g., thoracentesis, paracentesis, VAD placement).
v. Use only an electric razor for shaving.
vi. Protect skin from cuts and burns. Immediately cleanse
and treat any wound that breaks the skin.
vii. Use a soft toothbrush for frequent (minimum of three
to four times daily) oral care. Allow toothbrush to dry
before storing (Brown, 2010).
(g) Protective measures that patients can follow (Brown, 2010;
OLeary, 2010; Shelton, 2011)
i. Report fever, chills, and other signs and symptoms of
infection at onset.
ii. Personal hygiene
Wash hands frequently with soap and water or an
antiseptic hand rub. Hands may remain colonized
with microorganisms if they are not dried properly after washing.
Bathe daily.
Avoid activities that may compromise skin integrity.
Wear gloves when working in the garden.
Perform frequent (three to four times per day) oral
assessment and care.
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Chapter 9. Side Effects of Cancer Therapy

Cleanse the perineal area from front to back after


toileting.
Avoid exposure to pathogens or people who are experiencing signs and symptoms of contagious conditions.
iii. Protective measures
Do not share eating utensils.
Do not eat meat or produce that has not been either cooked or washed.
Adhere to safe food handling practices, and avoid
consuming food when safety of preparation, storage, or serving is not guaranteed.
Do not provide direct care for pets or farm animals;
avoid contact with animal excreta.
Refrain from direct or indirect contact with reptiles, fish, and birds.
Avoid exposure to fresh or dried plants and flowers because of risk of Aspergillus infection. Plant care
may be done by staff not directly providing care to
the patient.
Do not enter, travel through, or stay in an area of
construction or renovation or where construction
material or debris has been placed or where fields
have recently been plowed.
Consider vaccination for influenza and pneumonia (CDC, 2011).
Avoid contact with people who have been vaccinated with a live vaccine within the past 30
days.
(2) Management of neutropenic fever: Use of CSFs after a patient
is diagnosed with febrile neutropenia is not recommended (de
Naurois et al., 2010; Freifeld et al., 2011). To manage neutropenic fever, the clinician should take the following steps.
(a) Obtain cultures (NCCN, 2013f).
i. Urine: If symptomatic, with catheter, or if urinalysis
is abnormal
ii. Blood: Two sets (one set includes two bottles). If patient has a central VAD, options include
One peripheral and one central VAD, which may
assist in identifying central VAD as the source of
bloodstream infection
Both peripheral
Both from central VAD.
iii. Stool: For diarrhea, obtain Clostridium difficile assay
and enteric pathogen screen.
iv. Skin: Aspirate/biopsy skin lesions. Vesicular or ulcerated skin lesions require viral cultures.
v. VAD cutaneous site: Consider routine fungal/Mycobacterium culture if inflammation is present.
vi. Throat/nasopharynx: When respiratory viral symptoms are present, especially during seasonal outbreaks
(b) Conduct site-specific history and physical examination with
attention to identifying the source of infection (NCCN,
2013f).
i. Assess VADs, skin, lungs, sinus, mouth, pharynx, esophagus, bowel, rectum, and perivaginal and perirectal areas for signs and symptoms of infection.
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ii. Obtain historical data including comorbidities, date


and regimen of last chemotherapy, previous infections,
recent antibiotic therapy/prophylaxis, medications,
and human immunodeficiency virus (HIV) status. Explore exposure risks, including anyone at home with
similar symptoms, pets, travel, recent blood product
transfusion, or exposure to tuberculosis.
(c) Obtain a chest x-ray if respiratory symptoms are present.
(d) Once initial cultures have been obtained, administer empiric broad-spectrum antibiotics as ordered until organism
source is identified.
(e) Monitor blood culture reports daily and anticipate antibiotic therapy based on findings.
4. Anemia
a) Erythropoiesis: The process of erythrocyte (RBC) production in the
bone marrow (Bell et al., 2009; Dessypris & Sawyer, 2009)
(1) The kidneys are the primary producers of erythropoietin (EPO),
the growth factor that stimulates pluripotent stem cells to produce RBCs.
(2) RBC production is regulated by oxygen levels. When oxygen
levels are low, the kidney releases EPO to stimulate pluripotent
stem cells to produce more RBCs.
b) Normal physiology of erythrocytes (see Figure 21) (Bell et al.,
2009)
(1) In the bone marrow, the pluripotent stem cell becomes an
erythrocyte via a series of maturation phases that takes about
five days. The five major stages follow.
(a) The earliest identifiable stage is the pronormoblast (rubricyte). These cells take about 12 hours to divide into basophilic normoblast daughter cells.
(b) In approximately 20 hours, the normoblast cells continue maturation marked by accumulation of more RNA and
Hgb. When they divide, they become polychromatophilic normoblasts.
(c) Polychromatophilic normoblasts are smaller than their
precursor cells, and nucleoli are no longer visible. Proliferation is apparent in this phase (about 30 hours) as polychromatophilic normoblasts outnumber cells in earlier
development by 3:1. Under normal circumstances, polychromatophilic normoblasts are absent in adult peripheral blood. Small numbers are normal in the peripheral
blood of newborns.
(d) Orthochromatic normoblasts are derived in about 48 hours
from polychromatophilic normoblasts. In this phase, the
nucleus is unable to synthesize DNA, thereby ending cell
division.
(e) In the polychromatophilic erythrocyte (reticulocyte)
phase, the nucleus is phagocytized after being pushed
out of the cell. The reticulocyte either remains in the
bone marrow for several days to mature or is released
and matures in the spleen for one to two days. At this
point, the erythrocyte holds approximately two-thirds of
its Hgb content.
(2) Without a nucleus, mature erythrocytes cannot synthesize Hgb.
They are able to transport oxygen from the lungs to tissue and,
because of their flexible form, move easily through microcirculation to do so.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9. Side Effects of Cancer Therapy

(3) Iron is essential for RBC production. Iron reaches the precursor cells bound to transferrin, where it is used for heme synthesis and stored as ferritin in bone marrow reticuloendothelial cells, liver, and spleen. Dietary sources provide and maintain iron stores.
(4) RBC mass and volume: Homeostasis of erythropoiesis is a continuous process driven by oxygen levels and EPO response. The
average number of circulating RBCs in adults ranges from 4.7
6.1/mm3 in men and 4.25.4/mm3 in women but can vary by
up to 10% (Hughes, 2009).
(5) EPO is a hormone primarily (90%) produced by the peritubular cells of the kidneys and to a lesser extent in the liver. The
plasma half-life of EPO is six to nine hours. Levels vary as they
respond to internal (e.g., decreased Hgb level) and external
(e.g., high altitude) signals of low oxygen tension within kidney tissue. During anemia or hypoxemia, EPO is secreted into
the plasma and stimulates activity of erythrocyte precursor cells.
As a result, the reticulocyte count is elevated by an early and
increased number of polychromatophilic cells released from
the bone marrow.
(6) RBC life span: A typical RBC has a life span of approximately
120 days in peripheral circulation (see Table 17). It travels 200
300 miles before being removed in a systematic process by macrophages. The turnover is generally 1% per day. The duration
of RBC life span, time for maturation in the bone marrow, and
low turnover explain why anemia occurs later than neutropenia and thrombocytopenia following myelosuppressive therapy (Camp-Sorrell, 2011).
c) Pathophysiology
(1) Many causes for anemia exist in patients with cancer. Myelosuppressive therapy, bone marrow involvement, inadequate EPO
levels, and RBC destruction all may contribute to the diagnosis
of anemia (Camp-Sorrell, 2011; Miller, 2010).
(2) Classification of anemia based on RBC size: Mean corpuscular
volume, which reflects the size of RBCs, is used in the differential diagnosis of microcytic, normocytic, or macrocytic anemia (see Table 18) (Glassman, 2009; Means & Glader, 2009;
Miller, 2010).
d) Incidence
(1) Many patients (40%70%) experience some degree of anemia during or following systemic chemotherapy (Calabrich
& Katz, 2011). Severity may increase with comorbidities, concurrent radiation therapy, and insufficient nutritional intake. The incidence of anemia in patients with hematologic
malignancies has been reported as three times higher than
in those with solid tumors (Birgegrd, Gascn, & Ludwig,
2006).
(2) Cancer diagnosis, frequency of treatments, regimen, and dosing schedule all may contribute to onset, severity, and duration
of anemia (Glassman, 2009).
e) Risk factors
(1) Medications that suppress bone marrow function, interfere with
erythrocyte development and function, or suppress EPO production (Bottomley, 2009)
(a) Platinum drugs are known to be nephrotoxic (Calabrich
& Katz, 2011).
(b) Biotherapies (e.g., alemtuzumab [Genzyme Corp., 2009a])
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Table 18. Classifications of Common Cancer-Related Anemias


Anemia Type

Description

Differential Diagnosis

Microcytic

Decreased MCV (< 80 fL)


RBCs small in size

Iron deficiency
Anemia of chronic disease
Thalassemia minor
Sideroblastic anemia

Normocytic

Normal MCV (80100 fL)


RBCs normal in size

Anemia of chronic disease


Hemolytic anemia
Aplastic anemia
Renal failure

Macrocytic

Increased MCV (> 100 fL)


RBCs large in size

B12 deficiency
Folate deficiency
Myelodysplastic syndromes

Low reticulocyte
count

Decreased RBC production


< 0.5%1.5% of erythrocytes

Anemia of chronic disease


Aplastic anemia
Iron deficiency
Vitamin B12 deficiency
Folate deficiency
Bone marrow suppression or infiltration

High reticulocyte
count

Increased RBC destruction


> 0.5%1.5% of erythrocytes

Hemolysis
Chemotherapy-induced
Autoimmune

fLfemtoliters; MCVmean corpuscular volume; RBCred blood cell


Note. Based on information from Loney & Chernecky, 2000; Lynch, 2006.
From Cancer-Related Anemia: Clinical Review and Management Update, by B. Hurter and N.J. Bush,
2007, Clinical Journal of Oncology Nursing, 11, p. 350. doi:10.1188/07.CJON.349-359. Copyright 2007 by
Oncology Nursing Society. Reprinted with permission.

(c) Antituberculosis agents: Isonicotinylhydrazine (isoniazid),


pyrazinamide, and cycloserine (Bottomley, 2009)
(d) High-dose chemotherapy for HSCT
(2) Malignancies that originate or metastasize to the bone marrow
and suppress RBC precursors
(3) Radiation therapy to areas of the skeleton involved with hematopoiesis (NCCN, 2013c)
(4) Acute or chronic blood loss directly related to tumor invasion
(5) Advanced age: Places patients at risk for anemia of malignancy (Mayden, 2011)
(6) Poor nutrition: Anorexia, nausea, vomiting, stomatitis, early
satiety, and diarrhea may contribute to decreased oral intake
and absorption of nutrients. Lack of calorie, protein, vitamin,
and mineral intake, reflected in weight loss or weakness, compromises cellular functions, including erythrocyte production
(Cunningham & Huhmann, 2011; Miller, 2010).
(7) Comorbidities
(a) Renal insufficiency: Chemotherapy agents known to have
nephrotoxic properties (e.g., cisplatin, carboplatin) place
patients at risk because kidney function is essential for
EPO production. When EPO levels are low, more hypoxia is required to stimulate EPO response (Dessypris &
Sawyer, 2009).
(b) Alcohol abuse and liver dysfunction (Bottomley, 2009)
(c) Cardiopulmonary disease (Means & Glader, 2009; NCCN,
2013c)
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9. Side Effects of Cancer Therapy

(8) Female gender (Spivak, Gascn, & Ludwig, 2009)


f) Clinical manifestations (Means & Glader, 2009)
(1) Cardiopulmonary
(a) Dyspnea, hypoxia
(b) Tachycardia, heart murmurs
(c) Orthostatic hypotension
(2) Integumentary
(a) Pallor of oral mucous membranes, conjunctivae, lips, nail
beds, and palms of hands or soles of feet
(b) Hair loss, thinning, and early graying
(c) Brittle fingernails and toenails
(d) Cyanosis
(e) Hypothermia
(3) Neuromuscular
(a) Headache, dizziness
(b) Drowsiness, restlessness, inability to concentrate
(c) Paresthesias
(d) Fatigue, weakness
(4) Decreased urine output
g) Adverse outcomes (Calabrich & Katz, 2011; Spivak et al., 2009)
(1) Because low tissue oxygenation is related to reduced sensitivity of tumors to radiation therapy and some chemotherapy, hypoxia may adversely affect treatment outcomes.
(2) Low oxygen levels are directly associated with fatigue and weakness and may adversely affect QOL.
(3) Hypoxic tissue promotes angiogenic factors that may contribute to tumor growth.
(4) Postoperative mortality is increased in the presence of anemia.
(5) Survival times of anemic patients are shorter compared to those
without anemia for most tumor types.
h) Management (Mitchell, 2010a)
(1) Fatigue is an early and frequent symptom of anemia with significant negative impact on QOL. Interventions should be aimed
at identifying and managing fatigue.
(a) Encourage frequent rest periods to conserve energy.
(b) Use exercise when benefits outweigh risks.
(c) Explore complementary therapies (e.g., relaxation, massage, healing touch [Mitchell, Beck, Hood, Moore, & Tanner, 2009]) with potential to minimize fatigue.
(d) Assess nutritional intake for adequate content and quantity.
(e) Teach patients and significant others the importance of
hydration.
(2) Monitor laboratory results related to anemia (see Table 19)
and take appropriate action when abnormal (e.g., B12 and iron
deficiencies).
(3) Interventions for hypoxia
(a) Provide supplemental oxygen.
(b) Teach energy conservation.
(c) Consider measures to increase Hgb (Lemoine & Gobel,
2011).
i. Blood transfusions
ii. Erythropoiesis-stimulating agents (ESAs) (see Table 20)
iii. The manufacturers black box warning is supported
by eight randomized studies that each demonstrated decreased overall survival and locoregional conCopyright 2014 by the Oncology Nursing Society. All rights reserved.

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Table 19. Laboratory Assessment of Anemia: Normal Values (Adults)


Laboratory Test

Normal Value

Red blood cell count

Male: 4.76 million cells/mcl; female: 4.25.4 million cells/mcl

Hemoglobin

Male: 13.518 g/dl; female: 1216 g/dl

Hematocrit

Male: 42%52%; female: 37%47%

Mean corpuscular volume

78100 fL

Mean corpuscular hemoglobin

2731 pg/cell

Red cell distribution width

11.5%14%

Reticulocyte count

0.5%1.85% of erythrocytes

Ferritin

Male: 20300 ng/ml; female: 15120 ng/ml

Serum iron

Male: 75175 mcg/dl; female: 65165 mcg/dl

Total iron-binding capacity

250450 mcg/dl

Serum erythropoietin level

Male: 17.2 mU/ml; female: 18.8 mU/ml

Coombs test (direct and


indirect)

Negative

Serum B12

190900 pg/ml

Serum folate

> 3.5 mcg/L

Note. Based on information from Cullis, 2011; Knovich et al., 2009; Van Vranken, 2010.
From Anemia of Chronic Disease, by B. Faiman in D. Camp-Sorrell and R.A. Hawkins (Eds.), Clinical Manual for the Oncology Advanced Practice Nurse (3rd ed.), in press, Pittsburgh, PA: Oncology Nursing Society.
Copyright 2014 by the Oncology Nursing Society. Reprinted with permission.

trol when ESAs were used in patients diagnosed with


advanced breast, cervical, head and neck, lymphoid,
and non-small cell lung cancer. The FDA implemented a risk management program (known as a risk evaluation and mitigation strategy, or REMS), requiring prescribers of ESAs to enroll patients in the ESA
APPRISE (Assisting Providers and Cancer Patients
with Risk Information for the Safe Use of ESAs) Oncology Program. This program has prescriber and
patient requirements aimed at ensuring safe use of
these agents (Amgen Inc., 2012a; NCCN, 2013c).
5. Thrombocytopenia
a) Normal physiology of platelets (see Figure 21) (Bell et al., 2009)
(1) The thrombocyte (platelet) precursor megakaryocyte is the largest hematopoietic cell descending from the pluripotent stem
cell. The goal of thrombopoiesis is to produce and release mature platelets so that a normal level (150,000400,000/mcl) is
circulating at any given time.
(2) The major steps in thrombopoiesis
(a) Maturation begins with megakaryoblasts that increase in
amounts of cytoplasm and nuclear components as they become promegakaryocytes.
(b) During the promegakaryocyte phase, the nucleus continues to enlarge and becomes lobulated in preparation for
the megakaryocyte phase.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 20. Growth Factors


Classification
Colonystimulating
factor

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Darbepoetin
(Aranesp)

SC, IV

Treatment of anemia associated with


chronic renal failure whether or not the
patient is receiving dialysis
Treatment of anemia in patients where
anemia is caused by concomitantly administered chemotherapy and, upon initiation, there is a minimum of two additional months of planned chemotherapy

Shortness of breath, cough,


low blood pressure during
dialysis, abdominal pain,
edema of arms and legs,
hypertension, skin rash,
urticaria, pure red cell
aplasia, myalgia, infection,
fatigue edema, diarrhea,
thrombotic events

Increased risk of death and serious


cardiovascular events exists if administered when hemoglobin is >
12 g/dl.
Ensure adequate iron stores in patients prior to and during use.
Agent may be administered every 1,
2, or 3 weeks, but dosing schedule
should be consistent.
Use lowest effective dose.
Do not shake vials or syringes containing drug.
Store in refrigerator.
Do not freeze.
(Amgen Inc., 2012a)

Stimulates erythropoiesis via the


same mechanism as endogenous erythropoietin

Epoetin alfa
(Procrit,
Epogen)

SC

Treatment of anemia associated with renal


failure whether or not the patient is receiving dialysis
Treatment of anemia associated with treatment using zidovudine in HIV-infected
patients
Treatment of anemia in patients with nonmyeloid malignancies where anemia is
caused by concomitant use of chemotherapy for minimum of two months
Treatment of anemia in patients scheduled
to undergo elective noncardiac, nonvascular surgery to reduce the need for allogeneic red blood cell transfusions
Contraindicated when goal of chemotherapy is curative

Hypertension, skin rash, urticaria, pure red cell aplasia, myalgia, infection, fatigue, edema, diarrhea,
thrombotic events

Increased risk of death and serious


cardiovascular events exists if administered when hemoglobin is >
12 g/dl.
Ensure adequate iron stores in patients prior to and during use.
Agent may be given three times
weekly or once weekly.
Use lowest effective dose.
Do not shake vials or syringes containing drug.
Store in refrigerator.
Do not freeze.
(Amgen Inc., 2012b; Janssen Products, LP, 2012)

185

(Continued on next page)

Chapter 9. Side Effects of Cancer Therapy

Stimulates erythropoiesis via the


same mechanism as endogenous erythropoietin

186

Table 20. Growth Factors (Continued)

Colonystimulating
factor (cont.)

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Regulates the
production of
neutrophils within the bone marrow

Filgrastim
(G-CSF,
Neupogen)

SC, IV

To decrease the incidence of infection in


patients with nonmyeloid malignancies
who are receiving myelosuppressive
cancer therapies associated with severe
neutropenic fever
To reduce the time to neutrophil recovery
and duration of fever following induction
or consolidation chemotherapy in patients with AML
To reduce the duration of neutropenia and
associated sequelae in patients receiving myeloablative chemotherapy prior to
marrow transplant
To mobilize hematopoietic progenitor cells
into peripheral blood for collection via
leukapheresis
For chronic administration to reduce the
incidence and duration of sequelae of
neutropenia in patients with congenital,
cyclic, or idiopathic neutropenia

Allergic reactions including


urticaria, rash, and facial
edema; acute respiratory distress syndrome, nausea, vomiting, bone pain
secondary to rapid growth
of myeloid cells in the
bone marrow, fever, severe sickle-cell crisis in patients with sickle-cell disorder; risk of rare splenic rupture

Store in refrigerator.
Do not freeze.
Agent may be diluted with 5% dextrose in water.
Do not dilute with saline solutions.
Do not shake.
Filgrastim is not to be administered in
the 24 hours prior to chemotherapy
through 24 hours after chemotherapy completion. SC dosing continues
daily up to 14 days, until postnadir
ANC > 10,000/mm3 is achieved.
(Amgen Inc., 2013a)

Regulates the
production of
neutrophils within the bone marrow

Pegfilgrastim
(Neulasta)

SC

To decrease the incidence of infection related to neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive chemotherapy

Allergic reactions including urticaria, rash, and facial edema; acute respiratory distress syndrome,
nausea, vomiting, bone
pain secondary to rapid growth of myeloid cells
in the bone marrow, fever,
sickle-cell crisis in patients
with sickle-cell disorder; injection-site reaction; risk of
rare splenic rupture

Pegfilgrastim is cleared by neutrophil


receptor binding with serum clearance directly related to number of
neutrophils. Do not administer in
the period beginning 14 days before
until 24 hours after administration of
cytotoxic chemotherapy.
Administer as a single 6 mg injection
once per chemotherapy cycle.
The 6 mg fixed dose should not be
administered to children or adolescents weighing < 45 kg.
Store in refrigerator.
Do not freeze.
Do not shake.
(Amgen Inc., 2012c)

(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 20. Growth Factors (Continued)


Classification

Mechanism
of Action

Drug

Route of
Administration

Indications

Side Effects

Nursing Considerations

Induces committed progenitor cells to divide


and differentiate in the granulocyte-macrophage pathways
including neutrophils, monocytes/macrophages, and myeloid-derived
dendritic cells

Sargramostim (GMCSF, Leukine)

SC, IV

Following induction chemotherapy in patients with AML to shorten neutrophil recovery and reduce incidence of infection
In patients for the mobilization of hematopoietic progenitor cells for collection via
leukapheresis and to speed engraftment
following autologous transplantation of
progenitor cells
To accelerate myeloid recovery following
allogeneic BMT
In patients with failure of engraftment following BMT

Edema, capillary leak syndrome, pleural or pericardial effusions, dyspnea, fever, abdominal pain, headache, chills, diarrhea, occasional transient supraventricular arrhythmia,
bone pain secondary to
rapid growth of myeloid
cells in the bone marrow

Dilute in NS solution for IV use.


Store in refrigerator.
Do not freeze.
Do not shake.
Do not administer through in-line filter.
Monitor CBC for elevated WBC and
platelet count.
Safety and effectiveness have not
been established for pediatric patients.
(Genzyme Corp., 2009b)

Leukocyte
growth factor
(short acting)

Binds to G-CSF
receptors and
stimulates proliferation of neutrophils

Tbo-filgrastim

SC

To reduce duration of severe neutropenia


in patients with nonmyeloid malignancies
receiving myelosuppressive anticancer
drugs associated with a clinically significant incidence of febrile neutropenia

Bone pain; allergic reactions including angioneurotic edema, dermatitis,


drug hypersensitivity, hypersensitivity, rash, pruritic rash, and urticaria; sickle-cell crisis; acute respiratory distress syndrome;
splenic rupture

Safety and effectiveness has not


been established in patients younger than age 18.
Administer first dose no sooner than
24 hours following chemotherapy
or within 24 hours prior to chemotherapy.
(Teva Pharmaceuticals USA, 2012d)

Thrombopoietic growth
factor

Stimulation of
megakaryocytopoiesis and
thrombopoiesis

Oprelvekin
(IL-11, Neumega)

SC

To prevent severe thrombocytopenia and


reduce the need for platelet transfusions
in patients with nonmyeloid malignancies
receiving chemotherapy with high risk of
severe thrombocytopenia

Anaphylaxis; dilutional anemia; diarrhea; dizziness;


fever; fluid retention resulting in peripheral edema,
pulmonary edema, dyspnea, capillary leak syndrome, atrial arrhythmias,
and exacerbation of preexisting pulmonary effusions; headache; nausea,
vomiting; insomnia; rhinitis; cough; injection-site reactions

Store in refrigerator.
Do not freeze.
Reconstitute with sterile water.
Should be used within 3 hours of reconstitution.
Do not shake or freeze following reconstitution.
Protect from light.
Dosing should begin 624 hours after completion of chemotherapy.
Discontinue when postchemotherapy platelet nadir > 50,000/mcl and
2 days before next chemotherapy cycle.
(Wyeth Pharmaceuticals, 2011)

187

AMLacute myeloid leukemia; ANCabsolute neutrophil count; BMTbone marrow transplantation; CBCcomplete blood count; G-CSFgranulocytecolony-stimulating factor; GM-CSFgranulocyte macrophage
colony-stimulating factor; HIVhuman immunodeficiency virus; ILinterleukin; IVintravenous; mclmicroliter; NSnormal saline; SCsubcutaneous; WBCwhite blood cell

Chapter 9. Side Effects of Cancer Therapy

Colonystimulating
factor (cont.)

188

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(c) When the cell reaches the megakaryocyte phase, invagination of the cytoplasm occurs to begin delineation of individual platelets.
(d) When the megakaryocyte completes maturation, its membrane ruptures and all of the cytoplasm separates into
platelets. One megakaryocyte is able to release thousands
of platelets.
(e) Platelets are released into circulation as the cytoplasm
extends through a basement membrane of the bone
marrow. Continued separation of the platelet-forming cytoplasm may occur after the cells reach the sinus.
The life span of circulating platelets is seven to eight
days (see Table 17). There is no reserve in the bone
marrow.
(3) When blood vessel wall integrity is damaged, platelets are
incorporated into the vessel wall and assist the endothelial cells in regaining vessel integrity by releasing platelet-derived growth factor (Harmening, Escobar, & McGlasson,
2009).
(4) Platelet plug formation involves adhesion and aggregation of
platelets in response to vascular damage. Platelets are able to
fulfill this vital role in hemostasis only when normal in number and function.
(5) Aggregation is a platelet-to-platelet interaction usually occurring 1020 seconds after loss of vascular integrity and platelet
adhesion.
(6) Secondary hemostasis is accomplished by fibrin clot formation.
If this process is flawed, decreased fibrin production and instability of the formed clot result.
b) Pathophysiology (Camp-Sorrell, 2011)
(1) Thrombocytopenia after chemotherapy is evident in approximately 814 days and is directly related to bone marrow suppression.
(2) Severity varies with drug, dose, and schedule.
(3) For some agents (e.g., gemcitabine, carboplatin, dacarbazine,
5-FU, lomustine, mitomycin C, thiotepa, trimetrexate), it is a
dose-limiting toxicity.
c) Risks and incidence: The following are known to cause thrombocytopenia (Kobos & Bussel, 2008).
(1) Myelosuppressive chemotherapy (e.g., carboplatin, gemcitabine)
or radiation therapy to marrow-producing skeletal sites
(2) Biotherapy (e.g., IFN)
(3) Comorbidities (e.g., liver disease)
(4) Destruction of platelets in the presence of autoimmune disease
(e.g., immune thrombocytopenic purpura) or disseminated intravascular coagulation (DIC)
(5) Bone marrow infiltration of primary or metastatic malignancies
(6) Drug therapy affecting platelet function (Rodriguez & Gobel,
2011)
(a) Aspirin
(b) Nonsteroidal anti-inflammatory drugs (NSAIDs)
(c) Quinine and quinidine
(d) Thiazide diuretics (e.g., furosemide)
(e) Benzene and benzene derivatives
(f) Tricyclic antidepressants
(g) Antibiotics
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9. Side Effects of Cancer Therapy

i. High-dose beta-lactam antibiotics (e.g., piperacillin,


ampicillin)
ii. Cephalosporins and moxalactam
(h) Heparin
(7) Herbal agents (e.g., ginkgo, garlic, ginger, turmeric)
d) Clinical manifestations (Camp-Sorrell, 2011; Rodriguez & Gobel, 2011)
(1) Cardiopulmonary
(a) Adverse changes in peripheral pulses, tachycardia, hypotension, orthopnea
(b) Dyspnea, tachypnea, adventitious breath sounds, hemoptysis
(2) Head and neck
(a) Petechiae of oral or nasal membranes
(b) Epistaxis
(c) Periorbital edema, subconjunctival hemorrhage, eye pain,
blurred or double vision
(3) Integumentary system
(a) Petechia, bruising, pallor, or acrocyanosis anywhere on skin
or mucous membranes
(b) Bleeding from surgical, device, or wound sites
(4) Neurologic
(a) Change in mental status, confusion, restlessness, lethargy
(b) Widening pulse pressure, abnormal change in pupil
size, diminished reflexes, loss of motor strength or coordination
(c) Headache or seizures
(5) Gastrointestinal
(a) Abdominal pain or distention
(b) Rectal bleeding, tarry stools, hematemesis
(c) Enlarged, palpable spleen
(6) Genitourinary
(a) Menorrhagia
(b) Hematuria, dysuria, low urine output
e) Management
(1) Monitor laboratory findings and take appropriate action.
(a) Obtain platelet count, prothrombin time, partial thromboplastin time, Hgb, Hct, D-dimer, fibrinogen, and fibrin.
(b) Test stool, urine, and emesis for occult blood.
(2) Maintain safe environment.
(a) Instruct patients to avoid activities that may cause injury.
(b) Assess the home environment and promote the use of nonskid rugs, nightlights, and ambulatory assistive devices to
prevent falls.
(3) Educate patients and families on ways to maintain skin integrity by (Camp-Sorrell, 2011; Rodriguez & Gobel, 2011)
(a) Using soft toothbrush
(b) Blowing nose gently
(c) Using electric razor versus straight blade razor
(d) Using emery board versus metal nail files
(e) Using water-soluble lubricants for sexual intercourse
(f) Avoiding any sexual activity that may compromise skin or
mucous membrane integrity
(g) Avoiding use of tampons
(h) Using laxatives or stool softeners to avoid constipation
(i) Refraining from using mechanical oral irrigation or aggressive dental flossing
(j) Avoiding dental and other invasive procedures.
(4) Medications and treatments (Rodriguez & Gobel, 2011)
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

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190

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(a) Administer platelet transfusions.


(b) Consider administering IL-11 (oprelvekin) (see Table
20).
B. GI and mucosal side effects
1. Nausea and vomiting: Nausea and vomiting (n/v) are two of the
most feared side effects of cancer treatment (NCI, 2011a). Healthcare providers underestimate the incidence of nausea (Grunberg,
2012). Emesis is better controlled than nausea (Basch et al., 2011).
Oncology nurses must be knowledgeable and proactive when treating
CINV.
a) Definitions
(1) Nausea is an unpleasant subjective experience that is described as a wavelike feeling occurring in the stomach and/
or back of the throat that may be accompanied by vomiting
(NCI, n.d.).
(2) The autonomic nervous system is involved in the development
of n/v. Physical manifestations include tachycardia, diaphoresis,
light-headedness, dizziness, pallor, excess salivation, and weakness (Camp-Sorrell, 2011).
(3) Retching is a rhythmic contraction involving the esophagus, diaphragm, and abdominal muscles in an attempt to eject stomach contents. Retching in the absence of vomiting is known as
dry heaves (Camp-Sorrell, 2011).
(4) Vomiting is the forceful expulsion of gastric, duodenum, or jejunum contents through the mouth (NCI, n.d.).
b) Pathophysiology
(1) Mechanisms of emesis (see Figure 23): Nausea, retching, and
vomiting are independent phenomena that can occur sequentially or as separate entities. The subjective nature of nausea
prevents a clear understanding of it; however, mechanisms of
vomiting related to chemotherapy administration are becoming better understood.
(a) Vomiting results from the stimulation of a complex process
that involves the activation of various pathways and neurotransmitter receptors (see Figures 23 and 24).
(b) Vomiting occurs when certain neural structures in the
brain stem, collectively called the vomiting center (VC),
are stimulated. The VC is activated by the visceral and
vagal afferent pathways from the GI tract, the chemoreceptor trigger zone (CTZ), the vestibular apparatus,
and the cerebral cortex. Decreased motility and reverse
motility occur when the VC is stimulated (Camp-Sorrell,
2011).
(c) Chemotherapy stimulates enterochromaffin cells, causing them to release serotonin (5-hydroxytryptamine-3
[5-HT3]). The vagus nerve plays a key role in emesis caused
by chemotherapy, radiation therapy to the epigastrium,
and abdominal distention or obstruction. Serotonin release causes the activation of the vagus nerve, which stimulates vomiting through either the CTZ or the VC (CampSorrell, 2011). Serotonin is primarily involved in acute n/v
(Rojas & Slusher, 2012).
(d) The CTZ, a highly vascular area, lies at the surface of
the fourth ventricle, close to the VC. The CTZ is not
confined within the blood-brain barrier. Therefore, it
can detect chemical stimuli in the cerebrospinal fluid
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Chapter 9. Side Effects of Cancer Therapy

191

Figure 23. Mechanics of Emesis

Sensory input (pain, smell, sight)

Higher cortical
centers

Histamine antagonists
Muscarinic antagonists
Dopamine antagonists
Cannabinoids
Neurokinin-1 receptor antagonists
Chemotherapy
Anesthetics
Opioids

Sphincter
modulators

Chemotherapy

Chemoreceptor
trigger zone
(area postrema, 4th
ventricle)

Benzodiazepines

Vomiting center
(medulla)

Neurokinin-1 receptor
antagonists
5-HT3-antagonists

Stomach
Small intestine

Surgery

Memory, fear, anticipation

Labyrinths

Surgery

Radiotherapy
Gastroprokinetic
agents

Neuronal pathways
Sites of action of drugs
Factors that can cause
nausea and vomiting

and the blood. The CTZ plays a role in CINV as well as


in emesis associated with other causes such as anesthetics and opioids.
(e) Substance P is found in vagal afferent neurons and binds
to neurokinin-1 (NK1) receptors, causing vomiting. Stimulation of the NK1 receptor by substance P is believed to be
the main trigger for delayed n/v, which led to the discovery of aprepitant, an NK1 receptor antagonist.
(f) Motion sickness and labyrinthitis are the most common
stimuli to the vestibular apparatus of the inner ear that induce n/v. The vestibular apparatus may play a minor role
in CINV. Surgery can induce vomiting through stimulation
of the vestibular system.
(g) Memory, fear, anticipation, pain, and an unpleasant smell
can trigger n/v at the cerebral cortex.
(h) Factors that can cause n/v include chemotherapy, biotherapy, targeted therapy, radiation therapy, surgery, opioids,
and other medications.
(i) Other potential causes of n/v (Rangwala, Zafar, & Abernethy, 2012)
i. Psychophysiologic (e.g., anxiety, anticipatory n/v)
ii. Bowel obstruction (partial or complete)
iii. Vestibular disturbance
iv. Brain metastasis
v. Hypercalcemia, hyperglycemia, or hyponatremia
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

192

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Figure 24. Neuroreceptors

Corticosteroid

Dopamine-2

Histamine

Neurokinin-1

Chemoreceptor Trigger Zone,


Vomiting and Vestibular Centers,
and GI Tract

Serotonin
(5-HT3)

Muscarinic

Cannabinoid

Opioid
Acetylcholine

Note. Based on information from National Comprehensive Cancer Network, 2013b.

vi. Uremia
vii. Gastroparesis
(2) Patterns of therapy-related emesis (NCCN, 2013b)
(a) Anticipatory n/v: A conditioned response that occurs most
commonly before treatment and can be triggered by a particular smell, taste, or sight
i. Anticipatory n/v can occur during treatment and
may last one to two days after therapy. This usually
is a result of a previous unpleasant experience with
uncontrolled n/v, and it may be worse in patients
with high levels of anxiety. Anticipatory nausea usually occurs after two or three cycles of chemotherapy. To minimize the risk of this side effect, adequate
antiemetic control with initial treatments is essential. Infants and young children usually do not experience anticipatory n/v.
ii. Incidence: Anticipatory n/v occurs in 18%57% of patients as a result of classical conditioning from stimuli associated with chemotherapy (e.g., odors, tastes
of drugs, visual cues). Nausea is more common than
vomiting (NCCN, 2013b).
iii. Risk factors that may increase susceptibility to anticipatory n/v (NCI, 2011a)
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9. Side Effects of Cancer Therapy

Having a history of poorly controlled CINV with


previous encounters
Being young or middle-aged (e.g., patients younger than age 50)
Being of female gender
Having high levels of anxiety prior to and during
treatment
Feeling warm, hot, dizzy, or sweaty after chemotherapy
Having a susceptibility to motion sickness
Having a history of pregnancy-induced n/v
Feeling generalized weakness after chemotherapy
(b) Acute n/v: Starts within minutes to hours after chemotherapy administration and may last up to 24 hours depending
upon the agent (NCCN, 2013b)
i. The type, dose, route, and administration schedule of
chemotherapy influence the severity and risk of acute
n/v (Roila et al., 2010).
ii. Combination chemotherapy may cause more n/v than
single-agent therapy. Antiemetics for combination
chemotherapy should be administered based on the
agent with the highest emetogenic potential (Basch
et al., 2011).
iii. Incidence is determined by the emetogenicity of
the chemotherapy agents (see Tables 21 and 22)
and whether pretreatment with an antiemetic agent
occurred (Basch et al., 2011; Camp-Sorrell, 2011;
NCCN, 2013b).
iv. Current treatment guidelines published by NCCN
and ASCO are based on four categories of emetogenic potential for IV antineoplastics: high, > 90%; moderate, 30%90%; low, 10%30%; and minimal, < 10%
(Grunberg et al., 2011; NCCN, 2013b).
v. Risk factors that increase susceptibility to acute n/v
(NCI, 2011a; NCCN, 2013b)
Type and dose of antitumor treatment used (see Tables 21 and 22)
Gender: Women experience more acute n/v
than men.
Age: Patients older than age 50 experience less
n/v than patients younger than 50.
Alcohol use: Patients with a history of chronic
or high alcohol intake generally have less severe
nausea than those without such a history (intake
less than four drinks per week) (Irwin, Lee, Rodgers, Starr, & Webber, 2012).
Advanced-stage disease
Fatigue
Pain
Tumor burden
Concomitant medical conditions (e.g., obstruction, pancreatitis, hepatic metastases)
Presence of strong taste disturbances during chemotherapy
High level of pretreatment anxiety
Susceptibility to GI distress
Poor performance status
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

193

194

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Table 21. Emetogenic Potential of Intravenous Antineoplastic Drugs


Incidence
High (90%100%)

Agent

Onset (hours)

Duration (hours)

Cisplatin (> 50 mg/m2)

16

2448+

Dacarbazine

13

112

Mechlorethamine

0.52

824

Melphalan: high dose

0.36

612

16

1224

14

1248

Cyclophosphamide (> 1,500 mg/m )

AC combination (doxorubicin or epirubicin + cyclophosphamide)

24

424

412

1224

Clofarabine

Arsenic trioxide

Aldesleukin (> 1215 MIU/m2)

Azacitidine

2427

Variable

46

24+

Carboplatin

Busulfan

Bendamustine

Lomustine

46

1224

Dactinomycin

25

24

Daunorubicin

Plicamycin

16

1224

Actinomycin D

112

2448

Cytarabine (> 200 mg/m2)

112

2448

Doxorubicin ( 60 mg/m2)

46

6+

612

24+

Ifosfamide (< 10 g/m2)

Interferon alfa ( 10 MIU/m2)

Irinotecan

112

2472

Ifosfamide ( 10 g/m )
2

Epirubicin (> 90 mg/m )


2

Doxorubicin (> 60 mg/m )


2

Streptozocin
Cytarabine: high dose (> 1 g/m )
2

Carmustine (> 250 mg/m )


2

Moderate (30%90%)

Carmustine ( 250 mg/m2)


Cisplatin (< 50 mg/m2)
Cyclophosphamide (< 1,500 mg/m2)

Procarbazine
Etoposide: high dose

Epirubicin ( 90 mg/m2)
Idarubicin

Melphalan
Methotrexate ( 250 mg/m )
2

(Continued on next page)

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9. Side Effects of Cancer Therapy

195

Table 21. Emetogenic Potential of Intravenous Antineoplastic Drugs (Continued)


Incidence
Moderate (cont.)

Agent
Temozolomide
Oxaliplatin

Low (10%30%)

Duration (hours)

16

24

Aldesleukin ( 12 MIU/m2)

Cabazitaxel

Cytarabine (100200 mg/m2)

46

6+

Docetaxel

Doxorubicin (liposomal)

Eribulin

5-Fluorouracil

36

24+

Mitomycin C

14

4872

Etoposide

Gemcitabine

Interferon alfa (> 510 MIU/m2)

Topotecan

612

2472

Ixabepilone

Methotrexate (> 50 mg/m2 but < 250 mg/m2)

Paclitaxel, albumin bound

Pemetrexed

Pentostatin

Pralatrexate

Romidepsin

Thiotepa

Paclitaxel

Bleomycin

36

2-Chlorodeoxyadenosine

Alemtuzumab

Asparaginase

Bevacizumab

Bortezomib

Cetuximab

Cytarabine (< 100 mg/m )

612

312

Decitabine (< 100 mg/m )

Mitoxantrone

Minimal (< 10%)

Onset (hours)

Cladribine
2

Denileukin diftitox
Interferon alfa ( 5 MIU/m )

Ipilimumab

48

6-Mercaptopurine

(Continued on next page)

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

196

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Table 21. Emetogenic Potential of Intravenous Antineoplastic Drugs (Continued)


Incidence
Minimal (cont.)

Agent

Onset (hours)

Duration (hours)

412

312

Nelarabine

Ofatumumab

Pegasparaginase

Peginterferon

48

Hydroxyurea

Teniposide

Vincristine

Vinorelbine

Fludarabine

Rituximab

Trastuzumab

Temsirolimus

Valrubicin

Methotrexate (< 50 mg/m2)

Vinblastine

ACanthracycline + cyclophosphamide; MIUmillion international units


Note. Based on information from Basch et al., 2011; Grunberg et al., 2011; National Comprehensive Cancer Network, 2013b.
From Chemotherapy Toxicities and Management (p. 473), by D. Camp-Sorrell in C.H. Yarbro, D. Wujcik, and B.H. Gobel (Eds.), Cancer Nursing: Principles
and Practice (7th ed.), 2011, Burlington, MA: Jones and Bartlett. Copyright 2011 by Jones and Bartlett. Adapted with permission.

History of hyperemesis during pregnancy or morning sickness throughout pregnancy


(c) Delayed n/v: Occurs at least 24 hours after chemotherapy
administration (NCCN, 2013b).
i. Chemotherapy metabolites may cause increased delayed n/v because of an ongoing effect on the CNS
and/or GI tract (Camp-Sorrell, 2011).
ii. Occurs commonly with cisplatin, carboplatin, cyclophosphamide, and doxorubicin
iii. Cisplatin is associated with the highest incidence of
delayed n/v and may last for up to 6 days.
iv. Patients who experience acute n/v are more likely to
have delayed n/v (Roila et al., 2010).
c) Risk factors
(1) Cisplatin-containing regimens (60%90% of patients) (Roila
et al., 2010)
(2) High-dose chemotherapy
(3) Cyclophosphamide, ifosfamide, doxorubicin
(4) Poorly controlled n/v with prior chemotherapy cycles
d) Assessment: Determine the potential causes of n/v, the specific type(s),
and the level of emetogenicity (see Tables 21 and 22). Refer to Table 23 for assessment of n/v.
(1) Chemotherapy (NCCN, 2013b)
(a) Evaluate the emetogenic potential of all chemotherapy
agents the patient will be taking and ensure the patient has
prescriptions for antiemetics.
(b) Use of oral antineoplastic therapy is increasing. It is important to consider the emetogenic potential of these
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9. Side Effects of Cancer Therapy

Table 22. Emetogenic Potential of Oral Antineoplastic Drugs


Level

Agent

High

Hexamethylmelamine
Procarbazine

Moderate

Cyclophosphamide
Temozolomide
Vinorelbine
Imatinib

Low

Capecitabine
Tegafur-uracil
Etoposide
Sunitinib
Fludarabine
Everolimus
Lapatinib
Lenalidomide
Thalidomide

Minimal

Chlorambucil
Hydroxyurea
Melphalan
Methotrexate
6-Thioguanine
Gefitinib
Sorafenib
Erlotinib
L-Phenylalanine mustard

Note. From MASCC/ESMO Antiemetic Guideline 2013 (Slide 16), by Multinational Association of Supportive
Care in Cancer, 2013. Retrieved from http://www.mascc.org/antiemetic-guidelines. Copyright 2013 by Multinational Association of Supportive Care in Cancer. All rights reserved worldwide. Reprinted with permission.

drugs and treat as appropriate (NCCN, 2013b) (see Table 22).


(2) Biotherapy (IFN or IL-2)
(a) Patients receiving biologic agents may experience n/v as
part of a flu-like syndrome (see Table 9 in Chapter 4).
(b) Biotherapy involving the infusion of mAbs may be associated with n/v during the infusion.
(3) Targeted therapies: Many targeted drugs, which are primarily
administered orally, have emerged in the past decade. Each one
is unique in terms of mechanism of action and side effects. The
majority of currently FDA-approved targeted drugs are associated with minimal to low n/v risk (Roila et al., 2010).
(4) Physical causes: Tumor obstruction, gastroparesis, constipation,
increased intracranial pressure, brain metastasis, vestibular dysfunction, uncontrolled pain
(5) Metabolic causes: Hypercalcemia, hyponatremia, hyperglycemia, uremia, increased creatinine
(6) Other medications (e.g., opioids, antibiotics)
(7) Psychological causes: Anxiety, fear, emotional distress
e) Potential complications of n/v
(1) Discomfort
(2) Delay of treatment
(3) Interference with QOL (e.g., impaired mobility, fatigue)
(4) Dehydration
(5) Metabolic disturbances
(6) Anorexia and weight loss
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Table 23. National Cancer Institutes Common Terminology Criteria for


Adverse Events: Nausea and Vomiting
Adverse Event
Nausea

Vomiting

Grade

Description

Loss of appetite without alteration in eating habits

Oral intake decreased without significant weight loss, dehydration, or malnutrition

Inadequate oral caloric or fluid intake; tube feeding, parenteral


nutrition, or hospitalization indicated

12 episodes (separated by 5 minutes) in 24 hours

35 episodes (separated by 5 minutes) in 24 hours

6 episodes (separated by 5 minutes) in 24 hours; tube feeding, total parenteral nutrition, or hospitalization indicated

Life-threatening consequences; urgent intervention indicated

Death

Note. From Common Terminology Criteria for Adverse Events [v.4.03], by the National Cancer Institute
Cancer Therapy Evaluation Program, 2010. Retrieved from http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03
_2010-06-14_QuickReference_8.5x11.pdf.

(7) Physical debilitation from malnutrition


(8) Straining of abdominal muscles
(9) Increased intracranial pressure
(10) Aspiration
f) Collaborative managementPharmacologic actions: See Table 24.
(1) The goal of antiemetic therapy is complete control of CINV
(NCCN, 2013b).
(a) Choose antiemetics appropriate to the chemotherapeutic regimen.
(b) Consider level of emetogenicity based on route of administration and dose administered. Choose antiemetic regimen based on the drug with the highest emetogenicity
along with patient-specific risk factors (Roila et al., 2010).
(c) Patient response to pharmacologic interventions for n/v
may change over time and requires frequent assessment
and modification as appropriate (Basch et al., 2011).
(d) Administer antiemetics to cover the expected emetogenic
period of the chemotherapy agent, considering the duration and pattern of emesis. Antiemetics should be administered each day of chemotherapy and for two days after
the completion of chemotherapy as appropriate (Basch et
al., 2011).
(e) Note: Steroids may be contraindicated for patients receiving biotherapy agents because of their immunosuppressive
effects. This is agent-specific and should be considered prior to use. The benefit of steroids for minimizing hypersensitivity reactions or treating n/v may outweigh the risks related to immunosuppression. Glucocorticoids are contraindicated with IL-2 and IFN therapy (NCCN, 2013b).
(2) To manage acute n/v (NCCN, 2013b)
(a) For patients receiving IV agents categorized as high risk
(> 90% frequency) of emesis: Use a three-drug combination of a 5-HT3 antagonist, an NK1 antagonist, and a corticosteroid before chemotherapy. Alternatively, an olanzapine-containing regimen may be used consisting of olanzapCopyright 2014 by the Oncology Nursing Society. All rights reserved.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 24. Commonly Used Agents for the Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting
Classification

Mechanism
of Action

Drug

Route, Dose, and Schedule

Indications

Side Effects

Nursing Considerations

Action in multiple CINV receptor sites

Olanzapine

2.55 mg PO BID

Breakthrough n/v

Dry mouth, weight gain,


dizziness, sedation

Drug is contraindicated in older adult patients with dementia.

Anxiolytic

CNS depressant,
interferes with
afferent nerves
from cerebral
cortex causing
sedation

Alprazolam

0.52 mg PO TID beginning


the night before treatment

Prevention of anticipatory n/v

Sedation, confusion,
hyperactivity, agitation, dizziness, lightheadedness, hallucinations

Decrease starting dose to 0.25 mg PO BID


or TID in older adult patients, patients with
advanced liver disease, or patients with
other pertinent comorbidities.

CNS depressant,
interferes with
afferent nerves
from cerebral
cortex causing
sedation

Lorazepam

0.52 mg PO, sublingual or IV;


every 46 hours
For anticipatory n/v: 0.52 mg
PO beginning the night before to treatment and the
morning of treatment

Prevention of anticipatory n/v


In combination with other
antiemetics as needed
for acute or delayed n/v

Sedation, confusion,
hyperactivity, agitation, dizziness, lightheadedness, hallucinations

Use with caution in older adult patients or


those with hepatic or renal dysfunction.
Give first dose the night before treatment
and the morning of chemotherapy for anticipatory n/v.

Interacts with
cannabinoid receptors

Dronabinol

510 mg PO every 3 or 6
hours.

Treatment of CINV after standard antiemetics


have failed

Sedation, vertigo, euphoria, dysphoria, dry


mouth, tachycardia,
orthostasis

Incidence of paranoid reactions or abnormal thinking increases with maximum


doses.
Use with caution in patients with history of
psychiatric illness.

Nabilone

12 mg PO BID
Maximum recommended dose
is 6 mg given in divided doses TID.

Treatment of CINV after standard antiemetics


have failed

Sedation, vertigo, euphoria, dysphoria, dry


mouth, tachycardia,
orthostasis

Incidence of paranoid reactions or abnormal thinking increases with maximum


doses.
Use with caution in patients with history of
psychiatric illness.

Cannabinoid

Corticosteroid

Antiprostaglandin synthesis activity

Dexamethasone

12 mg IV or PO day 1 of chemotherapy; 8 mg IV or PO
days 24 of chemotherapy

Prevention of n/v caused


by highly and moderately emetogenic chemotherapy
Prevention of delayed n/v

Administer slowly over


at least 10 minutes
to prevent perianal
or vaginal burning or
itching.
Insomnia, anxiety, acne

Adding a corticosteroid increases the efficacy of antiemetic regimens by 15%


25%. Add dexamethasone to 5-HT3 regimens.

Dopamine
antagonist

Blocks dopamine
receptors

Haloperidol

0.52 mg PO or IV every 46
hours

Prevention of delayed n/v


or treatment of breakthrough n/v

Sedation, extrapyramidal symptoms, dystonia, dizziness, orthostasis

Administering haloperidol with diphenhydra


mine 2550 mg PO or IV prevents extrapyramidal symptoms; occurs more commonly in younger patients.
Drug is highly sedating.

199

(Continued on next page)

Chapter 9. Side Effects of Cancer Therapy

Antipsychotic

Mechanism
of Action

Dopamine
antagonist
(cont.)

Neurokinin-1
antagonist

Neurokinin-1 receptor antagonist

Drug

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Route, Dose, and Schedule

Indications

Side Effects

Nursing Considerations

Metoclopramide

1040 mg PO or IV every 46
hours

Prevention of n/v caused


by moderately emetogenic chemotherapy
Prevention of delayed n/v
or treatment of breakthrough n/v

Sedation, extrapyramidal symptoms, dystonia, dizziness, orthostasis

Incidence of drowsiness is greater with high


doses.
Drug may cause diarrhea.

Prochlorperazine

Doses vary: 10 mg PO or IV
every 46 hours
Also available: 25 mg suppositories every 12 hours

Prevention of delayed n/v


or treatment of breakthrough n/v

Sedation, extrapyramidal symptoms, dystonia, dizziness, orthostasis

Drug is not used for pediatric patients.


Drug is highly sedating.

Aprepitant

Capsules: 125 mg PO day 1 of


chemotherapy, then 80 mg
PO days 2 and 3

Prevention of acute and


delayed CINV in combination with other antiemetics

Constipation, hiccups,
loss of appetite, diarrhea, fatigue

Drug is given in combination with a corticosteroid and 5-HT3 antagonist on day 1


and a corticosteroid on days 2 and 3.
Consider a 50% dose reduction of oral
methylprednisolone and dexamethasone
and a 25% dose reduction of IV methylprednisolone. (Aprepitant increases the
AUC of steroids 13-fold.)
Use with caution in patients receiving chemotherapy that is primarily metabolized
through CYP3A4.
Efficacy of oral and hormonal contraceptives during administration of aprepitant
may be compromised; use alternative or
backup contraception method.
Coadministration with warfarin may decrease INR; monitor closely.
Consider drug interactions prior to administration.

Fosaprepitant
dimeglumine

150 mg IV day 1 or 115 mg


day 1 followed by aprepitant 80 mg PO daily on days
2 and 3

Prevention of acute and


delayed CINV

Infusion-site reactions
(e.g., pruritus, induration, erythema3%),
hypersensitivity, constipation, hiccups,
loss of appetite, diarrhea, fatigue

Drug is given in combination with a corticosteroid and 5-HT3 antagonist on day 1.


Administer over 2030 minutes in a 150 ml
normal saline minibag (contraindicated
with lactated Ringers solution).
Consider a 50% dose reduction of oral
methylprednisolone and dexamethasone
and a 25% dose reduction of IV methylprednisolone. (Fosaprepitant increases
the AUC of steroids 13-fold.)
(Continued on next page)

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

200

Table 24. Commonly Used Agents for the Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting (Continued)

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 24. Commonly Used Agents for the Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting (Continued)
Mechanism
of Action

Drug

Neurokinin-1
antagonist
(cont.)

Neurokinin-1 receptor antagonist


(cont.)

Fosaprepitant
dimeglumine
(cont.)

Serotonin
antagonist

Serotonin receptor antagonist

Dolasetron

100 mg PO or 100 mg IV 30
minutes before chemotherapy

Prevention of acute CINV

Headache, diarrhea,
dizziness, fatigue, abnormal LFTs

Dolasetron precipitates with dexamethasone in D5W.


Dolasetron can be administered as a rapid IV bolus.

Granisetron

2 mg PO or 1 mg PO BID up to
1 hour before chemotherapy;
0.01 mg/kg (max 1 mg) IV 30
minutes before chemotherapy

Prevention of acute CINV

Headache, asthenia, diarrhea, constipation,


fever, somnolence,
QTc prolongation

Granisetron can be administered by rapid IV bolus.


Instruct patients to take oral formulation
with milk or food.

Granisetron
transdermal
(Sancuso)

Transdermal patch containing


34.3 mg of granisetron; one
patch delivers 3.1 mg per 24
hours. Apply a single patch
to the upper outer arm a
minimum of 2448 hours before chemotherapy.
Patch can be worn for up to 7
days (depending upon the
duration of the regimen). Remove patch a minimum of
24 hours after completion of
chemotherapy.

Prevention of n/v in patients receiving moderately and/or highly


emetogenic chemotherapy for up to 5 consecutive days

Constipation; may
mask a progressive
ileus and/or gastric
distention caused by
the underlying condition; headache, skin
rash, QTc prolongation

Drug is contraindicated in patients with


known hypersensitivity to granisetron or
any of the components of the patch.
Remove patch if severe skin reactions occur (allergic, erythematous, macular, or
papular rash or pruritus). Avoid direct exposure of application site to natural and
artificial light while wearing the patch and
for 10 days after removing it.

Ondansetron

1624 mg PO or 812 mg IV
(maximum 32 mg/day); infuse IV dose over 15 minutes; give 30 minutes before
chemotherapy.
Orally disintegrating tablet formulation: 8 mg

Prevention of n/v associated with single-day


highly and moderately
emetogenic chemotherapy in adults

Headache, diarrhea,
fever, constipation,
transient increase in
SGOT, SGPT, hypotension, QTc prolongation

Ondansetron and dexamethasone are compatible.

Classification

Route, Dose, and Schedule

Indications

Side Effects

Nursing Considerations
Use with caution in patients receiving chemotherapy that is primarily metabolized
through CYP3A4.
Efficacy of oral and hormonal contraceptives during administration of fosaprepitant may be compromised; use alternative
or backup contraception method.
Coadministration with warfarin may decrease INR; monitor closely.
Consider drug interactions prior to use.

Chapter 9. Side Effects of Cancer Therapy


201

(Continued on next page)

Serotonin
antagonist
(cont.)

Mechanism
of Action

Drug

Route, Dose, and Schedule

Indications

Side Effects

Nursing Considerations

Palonosetron

0.25 mg fixed IV dose; infuse


over 30 seconds; give 30
minutes prior to chemotherapy on day 1.
0.5 mg PO; give once, 30 minutes prior to chemotherapy
on day 1.

Prevention of acute n/v


associated with initial
and repeated courses
of moderately and highly emetogenic chemotherapy and the prevention of delayed n/v associated with initial and repeat courses of moderately emetogenic chemotherapy

Headache, constipation

Mean terminal elimination half-life is approximately 40 hours.


Palonosetron is the first 5-HT3 receptor antangonist approved for delayed n/v.
Repeat dosing within a 7-day interval is not
recommended until further evaluated.
Drug is not currently used for pediatric patients.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

AUCarea under the time-versus-concentration curve; BIDtwice daily; CINVchemotherapy-induced nausea and vomiting; CNScentral nervous system; D5W5% dextrose in water; 5-HT35-hydroxytryptamine-3; INRinternational normalized ratio; IVintravenous; LFTliver function test; n/vnausea and vomiting; POby mouth; QTcQT interval corrected; SGOTserum glutamic-oxaloacetic transaminase;
SGPTserum glutamic-pyruvic transaminase; TIDthree times daily
Note. Based on information from Camp-Sorrell, 2011; Irwin et al., 2012; Merck & Co., Inc., 2009; National Comprehensive Cancer Network, 2013b.

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Classification

202

Table 24. Commonly Used Agents for the Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting (Continued)

Chapter 9. Side Effects of Cancer Therapy

ine, palonosetron, and a corticosteroid. Lorazepam may be


used in combination with the aforementioned antiemetics
to improve control in high-risk regimens. Consider adding
an H2 blocker or proton pump inhibitor.
i. Administration of a corticosteroid with a 5-HT3 antagonist has been found to improve the control of
n/v when compared to a 5-HT3 antagonist alone and
is recommended for acute nausea in highly emetogenic regimens by NCCN (2013b), ASCO (Basch et
al., 2011), and the Multinational Association of Supportive Care in Cancer (MASCC) (Roila et al., 2010).
ii. If the antitumor regimen contains steroids (e.g., CHOP),
additional steroids are not needed (NCCN, 2013b).
iii. There is no difference in efficacy between IV and PO
5-HT3 antagonists (Basch et al., 2011).
iv. Anthracycline and cyclophosphamide regimens are
classified as highly emetogenic and should be treated
as such (Basch et al., 2011; NCCN, 2013b).
v. Oral aprepitant (days 13) and IV fosaprepitant (day
1 only) have equal efficacy (Basch et al., 2011).
vi. For patients receiving high-dose chemotherapy with
HSCT, a 5-HT3 antagonist combined with a corticosteroid is recommended (Basch et al., 2011).
(b) For patients receiving IV agents classified as moderate risk:
Use a two-drug combination of a 5-HT3 antagonist and a
corticosteroid. An NK1 antagonist and lorazepam may be
considered for select patients. Consider adding an H2 blocker or proton pump inhibitor.
i. NCCN (2013b) guidelines recommend palonosetron as
the preferred 5-HT3 antagonist. If it is not available, another 5-HT3 is acceptable. Alternatively, an olanzapinecontaining regimen may be used consisting of olanzapine, palonosetron, and a corticosteroid.
ii. Consider adding an NK1 antagonist for patients in
whom corticosteroids are contraindicated (Basch et
al., 2011).
(c) For patients receiving IV agents classified as low risk: Use
an agent such as a corticosteroid daily, metoclopramide,
prochlorperazine, or an oral 5-HT3 antagonist. Lorazepam
may be added. An H2 blocker or proton pump inhibitor
may be considered (NCCN, 2013b).
(d) For patients receiving IVs agents classified as minimal risk:
No routine prophylaxis is necessary. Ongoing assessment
for the occurrence of n/v should be performed. If n/v occurs, treat per low-risk guidelines (NCCN, 2013b).
(e) For patients receiving oral agents with high to moderate
risk: Use an oral 5-HT3 antagonist daily. Consider lorazepam oral or sublingual PRN and an H2 blocker or proton
pump inhibitor (NCCN, 2013b).
(f) For patients receiving oral agents with low to minimal risk:
Administer PRN antiemetics (e.g., metoclopramide, prochlorperazine, haloperidol), and if n/v occurs, add a 5-HT3
antagonist. Consider lorazepam and an H2 blocker or proton pump inhibitor if appropriate (NCCN, 2013b).
(g) For patients undergoing multiple consecutive days of chemotherapy: Each day, use antiemetics appropriate to the risk
category of the chemotherapy to be administered that day.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(3) To manage delayed n/v (NCCN, 2013b)


(a) Delayed n/v is a significant problem for patients with cancer who are receiving chemotherapy; prevention is the primary goal. NK1 antagonists and longer-acting 5-HT3 antagonists can help improve management of n/v in this setting.
(b) For patients at risk for delayed n/v (e.g., patients receiving
cisplatin) (NCCN, 2013b)
i. Use an NK1 antagonist in combination with a corticosteroid beginning on day 1 for delayed n/v.
ii. Use a single agent such as a corticosteroid, a 5-HT3
antagonist, or a dopamine antagonist.
iii. Consider adding lorazepam and an H2 blocker or proton pump inhibitor.
iv. Use a combination of the previously listed antiemetics
based on patient-specific needs (see Table 24).
v. Note: Metoclopramide is rarely used for pediatric patients.
(4) To manage anticipatory n/v: Use the most active antiemetic regimen appropriate to the chemotherapy being given. Such regimens must be used with the initial chemotherapy rather than
after assessment of the patients emetic response to less-effective treatment.
(a) Benzodiazepines (lorazepam or alprazolam) are the primary drugs used for the treatment of anticipatory n/v. Administer beginning the night before treatment (see Table
24) (NCCN, 2013b).
(b) Consider the addition of nonpharmacologic interventions
(e.g., relaxation, music therapy, hypnosis), which can be
helpful in this type of nausea [see g later in this section])
(NCCN, 2013b).
(5) For patients experiencing breakthrough n/v despite optimal
prophylaxis in current or prior cycles, ascertain that the best
regimen is being given based on the emetogenic potential of
the regimen (NCCN, 2013b).
(a) Conduct a careful evaluation of risk, antiemetic agents, disease, concurrent conditions, and medication factors.
(b) Consider adding an antianxiety agent to the regimen.
(c) Consider adding other antiemetic agents from different
drug classifications, using caution to avoid overlapping side
effects (see Table 24).
(d) Multiple agents used in combination may be required to
control n/v.
(e) Around-the-clock scheduling is suggested (NCCN, 2013b).
(f) Consider adding nonpharmacologic interventions in conjunction with antiemetics per patient preference.
g) Collaborative management: Nonpharmacologic interventions should
be used in conjunction with antiemetics.
(1) Music therapy is the controlled use of music to influence physiologic, psychological, and emotional responses. Music therapy may be beneficial to some patients at risk for CINV (Irwin
et al., 2012). It is often combined with other nonpharmacologic interventions. If music therapy is used, it should be in conjunction with antiemetics.
(2) The effectiveness of exercise as an intervention for n/v has not
been established. Further study is warranted (Irwin et al., 2012).
(3) Acupressure wristbands have been used with some success. Acupressure is a form of massage using pressure to localized areas
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9. Side Effects of Cancer Therapy

to reduce symptoms such as n/v (NCI, 2011a). In a Cochrane


Database systematic review (Ezzo et al., 2006), acupressure was
found to have no significant benefit for delayed n/v. This review found acupressure to have some benefit in acute nausea
but not vomiting.
(4) Acupuncture and electroacupuncture currently are being studied for the treatment of CINV.
(a) Acupuncture is the insertion of fine-gauge needles at specific points.
(b) Electroacupuncture is the use of electric pulses with acupuncture needles to increase stimulation.
(c) Research is needed to determine which of these treatments
may be more beneficial. Based on the results of studies to
date, acupuncture is likely to be effective for treatment of
CINV when combined with antiemetics. Further study is
needed to determine effectiveness in acute versus delayed
n/v when combined with currently recommended antiemetics (Ezzo et al., 2006).
(5) Behavioral interventions such as progressive muscle relaxation and guided imagery have been studied either alone or in
combination with pharmacologic agents to prevent or control
CINV. These behavioral methods have shown success and may
be used as adjunct therapies with pharmacologic interventions
(Irwin et al., 2012).
(6) Dietary interventions (NCI, 2011a)
(a) Encourage patients to eat small, frequent meals.
(b) Encourage patients to choose healthful foods.
(c) Encourage patients to avoid overeating.
(d) Medicate patients prior to meals so that the antiemetic effect is active during and immediately after eating.
(e) Consider medicating with an H2 blocker or proton pump
inhibitor to prevent dyspepsia, as it may mimic nausea.
(f) Encourage patients to avoid fatty, spicy, and highly salted
foods and foods with strong odors.
(g) Determine and repeat past measures that have been effective in controlling n/v.
(h) Encourage patients to eat cold or room-temperature foods
because these emit fewer odors than hot foods.
(i) Suggest that patients cook meals between chemotherapy regimens, when they are not nauseated, and freeze the
meals for later use, or suggest that another family member cook meals.
(j) Encourage patients to eat favorite foods when not experiencing n/v to prevent permanent dislike of these foods.
(k) Use ginger for CINV only per patient preference. Ginger is
thought to function as a 5-HT3 antagonist, NK1 antagonist,
antihistamine, and prokinetic (Haniadka, Rajeev, Palatty,
Arora, & Baliga, 2012). Effectiveness of ginger for CINV
has not been established and requires further study (Irwin
et al., 2012). Additional randomized controlled clinical trials using ginger with patients receiving chemotherapy are
needed to prove safety and benefit (Haniadka et al., 2012).
(l) Initiate dietary consult as needed.
h) Patient and family education
(1) Instruct adult patients to notify the staff if n/v persists for > 24
hours or if they are unable to maintain fluid intake. Ensure that
parents of pediatric patients know to notify staff if vomiting perCopyright 2014 by the Oncology Nursing Society. All rights reserved.

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

sists for more than two hours. In children, just a few hours of
vomiting can cause dehydration.
(2) Remind patients as necessary to take antiemetics before arriving for treatment. Ensure that antiemetics have been taken prior to administration of chemotherapy.
(3) Follow up 2448 hours after outpatient treatment to ensure adherence to and effectiveness of the antiemetic regimen (CampSorrell, 2011).
(4) Refer patient to educational resources such as NCIs Eating
Hints: Before, During, and After Cancer Treatment (NCI, 2009).
2. Diarrhea
a) Definition: Diarrhea is defined as loose or watery stools. Diarrhea resulting from administration of chemotherapy or specific biotherapy
agents is a frequent problem. Left untreated or inadequately treated,
diarrhea can lead to severe dehydration, hospitalization, treatment delays, dose reductions, and even death (Stein, Voigt, & Jordan, 2010).
b) Pathophysiology: The pathophysiology and etiology of diarrhea in
patients with cancer can be multifaceted. All possible causes of diarrhea need to be considered to treat the patient appropriately. The
most common mechanisms of chemotherapy-induced diarrhea are
osmotic, secretory, and exudative (NCI, 2012a).
(1) Osmotic diarrhea: Osmotic diarrhea usually is related to injury
to the gut, dietary factors, or problems with digestion. Water is
drawn into the intestinal lumen, resulting in increased stool volume and weight. Lactose intolerance is an example of this type
of diarrhea. New-onset lactose intolerance can occur in patients
undergoing cancer treatment (Andreyev, Davidson, Gillespie, Allum, & Swarbrick, 2012; Roy, Komanapalli, Shojamanesh, Bashir,
& Choudhary, 2013). Osmotic diarrhea is associated with large
stool volumes and sometimes is improved with fasting or elimination of the causative factor (e.g., lactose, sorbitol).
(2) Secretory diarrhea: The small and large intestines secrete more
fluids and electrolytes than can be absorbed. Infection and inflammation of the gut; damage to the gut caused by chemotherapy, radiation, or GVHD; and certain endocrine tumors
can cause secretory diarrhea. The imbalance between absorption and secretion leads to production of a large volume of fluid and electrolytes in the small bowel. This type of diarrhea is
associated with large volumes and may require a period of bowel rest with parenteral nutrition following by slow diet progression as tolerated (Muehlbauer, 2014).
(3) Exudative diarrhea: This type is caused by alterations in mucosal integrity, epithelial loss, enzyme destruction, and defective
absorption of the colon. Mucosal inflammation and ulceration
caused by inflammatory diseases, cancers, and cancer treatment
may result in the outpouring of plasma, proteins, mucus, and
blood into the stool, all of which can result in exudative diarrhea. This type of diarrhea is characterized by more than six
stools per day (Field, 2003).
c) Chemotherapy agents presenting the highest risk of diarrhea (Stein
et al., 2010)
(1) Irinotecan
(2) 5-FU
(3) Paclitaxel
(4) Dactinomycin
(5) Capecitabine
d) Examples of chemotherapy agents that may cause diarrhea
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9. Side Effects of Cancer Therapy

(1) Fludarabine
(2) Cytarabine
(3) Idarubicin
(4) Mitoxantrone
(5) Pentostatin
(6) Floxuridine
(7) Topotecan
(8) Cisplatin
(9) Oxaliplatin
(10) Docetaxel
(11) Pemetrexed
(12) Hydroxyurea
e) Biotherapy agents that may cause diarrhea
(1) IL-2
(2) IFNs
f) Targeted agents that may cause diarrhea
(1) mAbs: Ipilimumab is associated with diarrhea (32%, all grades),
abdominal pain, mucus or blood in stool, and immune-mediated enterocolitis. Loperamide and corticosteroids are used for
treatment. Discontinuation of ipilimumab may be necessary.
Evaluate abdominal pain with diarrhea for perforation or peritonitis, which has been reported with ipilimumab (Bristol-Myers
Squibb Co., 2013; Rubin, 2012) (see Table 10 in Chapter 4).
(2) Bortezomib
(3) Dasatinib
(4) Erlotinib
(5) Gefitinib
(6) Imatinib mesylate
(7) Lapatinib
(8) Lenalidomide
(9) Sunitinib
(10) Temsirolimus
(11) Thalidomide
(12) Vorinostat
g) Incidence of diarrhea following cytotoxic therapy
(1) The incidence of diarrhea varies greatly depending upon the
agent(s) used.
(2) The specific agent, dose, schedule, and combination with other
anticancer therapies all influence the severity of chemotherapyinduced diarrhea.
h) Clinical manifestations and consequences: If manifestations are severe, the course of action may be to modify or hold the causative
agent, which could compromise the benefit of the regimen. The clinical manifestations of diarrhea include the following (NCI, 2012a).
(1) Dehydration: Diarrhea dehydrates pediatric patients very quickly.
(2) Orthostasis
(3) Life-threatening hypokalemia, metabolic acidosis, hypercalcemia, malnutrition
(4) Cardiovascular or renal compromise
(5) Impaired immune function following frequent episodes of chemotherapy-induced diarrhea
(6) Perianal skin breakdown, discomfort, or infection
(7) Reduced absorption of oral medications
(8) Pain (abdominal cramping)
(9) Anxiety
(10) Exhaustion
(11) Decreased QOL
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i) Risk factors
(1) Radiation therapy to the pelvis, abdomen, or lower thoracic and
lumbar spine can lead to destruction of the cells of the lumen
of the bowel and can be an acute or chronic toxicity.
(2) 5-FU in combination with high-dose leucovorin (500 mg/m2)
or 5-FU administered as a weekly bolus (versus continuous infusion) (Goldberg et al., 2004)
(3) Irinotecan is associated with both acute and delayed diarrhea.
Irinotecan combined with bolus 5-FU and leucovorin is associated with increased morbidity and mortality related to diarrhea
(Pfizer Inc., 2012a; Stein et al., 2010).
(4) EGFR-targeted therapies (Stein et al., 2010)
(a) Grade 3 and 4 CTCAE (NCI CTEP, 2010) is < 10%.
(b) Cetuximab or panitumumab: Grade 2 is approximately 21%
and grade 3 is 1%2%.
(c) Small molecule EGFR tyrosine kinase inhibitors (e.g., erlotinib, gefitinib, lapatinib): All grades of diarrhea may occur in up to 60% of patients.
(5) Multitargeted tyrosine kinase inhibitors (Stein et al., 2010)
(a) Sorafenib and sunitinib: 30%50% incidence (all grades)
(b) Imatinib, a Bcr-Abl protein tyrosine kinase inhibitor: 30%
incidence although severe diarrhea is rare
(6) Immunosuppression
(7) Intestinal resection or gastrectomy
(8) Manipulation of bowel during surgery, which may cause diarrhea or ileus
(9) Intestinal infection secondary to mucositis and neutropenia
(e.g., infection with Rotavirus, Escherichia coli, Shigella, Salmonella, Giardia, or Clostridium difficile)
(10) GVHD
(11) Dietary causes (e.g., lactose intolerance; ingestion of caffeine, alcohol, or spicy or fatty foods; use of hyperosmotic dietary supplements)
(12) Inflammatory conditions, such as diverticulitis, irritable bowel
syndrome, or ulcerative colitis
(13) Malabsorption, partial bowel obstruction, bowel edema, motility disruption
(14) Anxiety and stress
j) Assessment: Accurate assessment is vital in determining the cause
and type of diarrhea; knowing the cause and type can be crucial to
proper treatment.
(1) Mistakenly using an antidiarrheal to treat diarrhea caused by
infection can intensify diarrhea severity and infectious complications (Curry, 2013).
(2) Irinotecan causes two distinct forms of diarrhea (early and late
onset), and each requires a different management strategy (see
Table 7 in Chapter 3).
(3) Fluoropyrimidine-induced diarrhea (e.g., 5-FU) risk factors
(Stein et al., 2010)
(a) Female gender
(b) Caucasian race
(c) Presence of diabetes
(4) Assess stool.
(a) Assess the pattern of elimination and stool character in relation to treatments (e.g., onset, duration, frequency, consistency, amount, odor, color).
(b) Assess for presence of nocturnal diarrhea, which can be
associated with diabetic autonomic neuropathy or infecCopyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9. Side Effects of Cancer Therapy

tions. Loss of sleep or interrupted sleep during the night


may increase fatigue.
(c) Grade diarrhea according to CTCAE criteria (NCI CTEP,
2010). See Table 25.
(d) Check for presence of blood or mucus in the stools.
(e) Monitor the patient for incontinence.
(5) Conduct a physical examination: The presence of fever, blood in
the stool, abdominal pain, weakness, or dizziness warrants medical
attention to rule out infection, bowel obstruction, and dehydration
(Benson et al., 2004). The steps of a physical examination follow.
(a) Auscultate for bowel sounds.
(b) Palpate and assess the abdomen.
(c) Assess for fecal impaction. Avoid manual rectal assessment
in patients who are thrombocytopenic or neutropenic.
(d) Look for signs of malnutrition, dehydration, electrolyte imbalance, and infectious process.
(e) Ask about pain experienced during or after defecation.
(f) Assess for fever, weakness, and dizziness.
(g) Determine if blood has been present in the stool (occult
or gross).
(h) Assess perianal area for skin breakdown and signs and symptoms of infection.
(6) Take a diet history (Engelking, 2008).
(a) Determine if dietary habits have changed. Be especially
aware of clues that indicate rapidly increased amount of
fiber in the diet.
(b) Assess for intake that could contribute to diarrhea (e.g., irritating foods, alcohol, coffee, fiber, fruit, lactose-containing foods/fluids, sorbitol-based gum, candy, herbal teas
that may contain laxatives).
(c) Assess for food or lactose intolerance or allergies.
(7) Take a medication history: Assess for use of the following (Micromedex, 2013; Muehlbauer, 2014).
(a) Antacids (especially those containing magnesium)
(b) Antibiotics
(c) Antihypertensives
Table 25. National Cancer Institutes Common Terminology Criteria
for Adverse Events: Diarrhea
Grade

Description

Increase of < 4 stools/day over baseline; mild increase in ostomy output compared
to baseline

Increase of 46 stools/day over baseline; moderate increase in ostomy output compared to baseline

Increase of 7 stools/day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self-care ADL*

Life-threatening consequences; urgent intervention indicated

Death

* Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications,
and not bedridden.
ADLactivities of daily living
Note. From Common Terminology Criteria for Adverse Events [v.4.03], by the National Cancer Institute
Cancer Therapy Evaluation Program, 2010. Retrieved from http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03
_2010-06-14_QuickReference_8.5x11.pdf.

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(d) Potassium or calcium supplements


(e) Diuretics
(f) Caffeine
(g) Theophylline
(h) NSAIDs
(i) Antiarrhythmic drugs
(j) Laxatives or stool softeners
(k) Promotility agents (metoclopramide)
(l) Magnesium oxide
(8) Assess for other possible contributing factors.
(a) Travel history (outside the United States)
(b) Use of alternative therapies (e.g., dietary supplements,
herbal remedies)
(c) Opioid withdrawal
(9) Take objective measurements (Engelking, 2008).
(a) Monitor intake and output.
(b) Monitor weight.
(c) Monitor laboratory data.
i. Check stool culture results for presence of infection.
ii. Check serum chemistries for electrolyte imbalance,
specifically potassium. Albumin may be decreased
with diarrhea.
iii. Assess complete blood count (CBC) to determine if
neutropenia or infection is present.
(d) Check skin turgor.
(e) Check vital signs.
k) Collaborative management
(1) Monitor number, amount, and consistency of bowel movements. For patients with colostomies, an increase in the number of loose stools daily should be monitored to assess for chemotherapy-induced diarrhea.
(2) Replace fluid and electrolytes, including potassium. Electrolytes
and fluids are absorbed in the small intestine. When diarrhea
occurs, these substances quickly pass through the small intestine without being absorbed. This can cause severe fluid and
electrolyte disturbances.
(3) Administer antidiarrheal medication as appropriate once infection has been ruled out. This will reduce stool frequency,
volume, and peristalsis. Reassess the severity of chemotherapyinduced diarrhea at the appropriate interval after antidiarrheal
medication. Table 26 lists antidiarrheal medications.
(a) NCCN currently does not have a guideline for management
of chemotherapy-induced diarrhea.
(b) Loperamide and octreotide are the only drugs that have established efficacy in chemotherapy-induced diarrhea. Further study is warranted to define the role of other pharmacologic interventions (Muehlbauer et al., 2009).
(4) Consider the use of antibiotics for patients with persistent diarrhea and signs of infection (Benson et al., 2004).
(5) Probiotics: The role of probiotics in chemotherapy-induced
diarrhea is an area of investigation. The appropriate strain(s),
dosage, and administration schedules need to be determined
(Guandalini, 2011; Muehlbauer et al., 2009).
(6) See Figure 25 for an example of chemotherapy-induced diarrhea treatment guidelines.
l) Patient and family education (Muehlbauer, 2014; NCI, 2012a): Provide the following instructions.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Table 26. Common Antidiarrheal Medications


Classification

Mechanism of Action

Drug

Route, Dose, and Schedule*

Side Effects*

Nursing Considerations*

Antimotility
agents

Slows GI transit time


and promotes reabsorption of water from
bowel; antiperistaltic

Diphenoxylate HCl
with atropine sulfate (Lomotil)

Adults: Individualize dosage. Initial


dose is 10 mg followed by 5 mg PO
QID; maximum dose is 20 mg/day.

Dry mouth, urinary retention, confusion, sedation, restlessness

Invasive bacterial diarrhea, pseudomembranous


colitis
In patients with advanced liver disease, drug may
precipitate hepatic coma.
Do not use in children younger than age 2.

Loperamide
(Imodium A-D)

Adults: 4 mg PO initially, followed by


2 mg PO after each unformed stool;
do not exceed 16 mg/day. Exception:
Doses are higher for late-onset irinotecan-induced diarrhea (2 mg every
2 hours).

Constipation, fatigue,
urinary retention,
drowsiness, dizziness

Invasive bacterial diarrhea


Do not use in children younger than age 2.

Inhibits growth hormone, glucagon, and


insulin; prolongs intestinal transit time; increases sodium and
water absorption

Octreotide (Sandostatin)

Adults: 100150 mcg SC or IV TID.


Doses may be escalated to 500 mcg
SC or IV TID or by continuous IV infusion 2550 mcg/hr.

Abdominal discomfort,
flatulence, constipation,
diarrhea, nausea, dizziness, headache, cardiac dysrhythmias, bradycardia

Drug may interact with insulin, oral hypoglycemic


medications, beta-blockers, or calcium channel
blockers. Insulin requirements may be decreased.
Observe for hyperglycemia/hypoglycemia.
Drug may decrease levels of cyclosporine when
given concurrently.
Drug may increase risk of developing gallstones.
Recommended after failure of Imodium or in patients with complicated diarrhea. Complicated diarrhea is defined as involving abdominal cramping, nausea and vomiting, fever, sepsis, neutropenia, or bleeding.
Sandostatin LAR Depot is under investigation for
the treatment of chemotherapy-induced diarrhea.

Anticholinergic

Antagonist of acetylcholine

Atropine

Adults: Used for early-onset cholinergic diarrhea (e.g., irinotecan induced),


0.251 mg PO or SC

Dry mouth, blurred vision, photophobia, constipation, xerostomia,


tachyarrhythmia

Antacids interfere with absorption of atropine.


Drug is contraindicated in patients with closedangle glaucoma.

Chapter 9. Side Effects of Cancer Therapy

Somatostatin
analog

* Consult product information for complete list of contraindications, drug interactions, and dosage ranges.
GIgastrointestinal; IVintravenous; POoral; QIDfour times daily; SCsubcutaneous; TIDthree times a daily

211

Note. Based on information from Benson et al., 2004; Engelking, 2008; Gibson & Stringer, 2009; Micromedex, 2013; Stein et al., 2010; and manufacturers prescribing information.

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Figure 25. Proposed Algorithm for the Assessment and Management of Treatment-Induced Diarrhea
EVALUATE
Obtain history of onset and duration of diarrhea
Describe number of stools and stool composition (e.g., watery, blood in stool, nocturnal)
Assess patient for fever, dizziness, abdominal pain/cramping, or weakness (i.e., rule out
risk for sepsis, bowel obstruction, dehydration)
Medication profile (i.e., to identify diarrheogenic agents)
Dietary profile (i.e., to identify diarrhea-enhancing foods)
UNCOMPLICATED
CTC grade 12 diarrhea
with no complicating
signs or symptoms

ADDED RISK FACTORS

MANAGEMENT
Stop all lactose-containing products, alcohol, and high-osmolar supplements
Drink 810 large glasses of clear liquids a day (e.g., Gatorade or broth)
Eat frequent small meals (e.g., bananas, rice, applesauce, toast, plain pasta)
Instruct patient to record the number of stools and report symptoms of life-threatening sequelae
(e.g., fever or dizziness upon standing)
For grade 2 diarrhea, hold cytotoxic chemotherapy until symptoms resolve and consider dose
reduction

COMPLICATED
CTC grade 3 or 4 diarrhea or grade
1 or 2 with one or more of the following signs or symptoms
Cramping
Nausea/vomiting ( grade 2)
Decreased performance status
Fever
Sepsis
Neutropenia
Frank bleeding
Dehydration

TREATMENT
Administer standard dose of loperamide: initial dose of 4 mg followed by 2 mg every 4 hours or
after every unformed stool
Consider clinical trial

Reassess 1224 hours later

Diarrhea resolving
Continue instruction for dietary modification
Gradually add solid foods to diet
Discontinue loperamide after 12-hour diarrheafree interval
RT-induced: Continue loperamide

Diarrhea unresolved

Progression to severe diarrhea


(NCI grades 34 with or without
fever, dehydration, neutropenia,
and/or blood in stool)

Persistent diarrhea (NCI grades 12)


Administer loperamide 2 mg every 2 hours
Start oral antibiotics
Observe patient for response
RT-induced: Oral antibiotics not generally recommended

Reassess 1224 hours later


Diarrhea resolved
Continue instructions for dietary modification
Gradually add solid foods to diet
Discontinue loperamide after 12-hour diarrheafree interval
RT-induced: Continue loperamide

Progression to severe diarrhea


(NCI grades 34 with or without
fever, dehydration, neutropenia,
and/or blood in stool)

Diarrhea unresolved

Persistent diarrhea (NCI


grades 12) (no fever, dehydration, neutropenia,
and/or blood in stool)

EVALUATE IN OFFICE/OUTPATIENT CENTER


Check stool workup (blood, fecal leukocytes, Clostridium difficile, Salmonella, Escherichia coli,
Campylobacter, infectious colitis)
Check CBC and electrolytes
Perform abdominal exam
Replace fluids and electrolytes as appropriate
Discontinue loperamide and begin second-line agent
Octreotide (100150 mcg SC TID with dose escalation up to 500 mcg TID)
Other second-line agent (e.g., tincture of opium)
RT-induced: Continue loperamide or other oral agent; no workup required

ADMIT TO HOSPITAL*
Administer octreotide (100150 mcg SC
TID or IV [2550 mcg/hr] if dehydration
is severe with dose escalation up to 500
mcg TID)
Start IV fluids and antibiotics as needed
(e.g., fluoroquinolone)
Stool workup, CBC, and electrolyte profile
Discontinue cytotoxic chemotherapy until
all symptoms resolve; restart chemotherapy at reduced dose

* For radiation-induced cases and select patients with chemotherapy-induced diarrhea consider intensive outpatient management, unless the patient has
sepsis, fever, or neutropenia.
CBCcomplete blood count; CTCCommon Toxicity Criteria; NCINational Cancer Institute; RTradiotherapy; SCsubcutaneous; TIDthree times
daily
Note. Based on information from Benson et al., 2004.
From Management of Cancer TreatmentRelated Diarrhea Issues and Therapeutic Strategies, by S. Kornblau, A.B. Benson III, R. Catalano, R.E. Champlin, C. Engelking, M. Field, S. Wadler, 2000, Journal of Pain and Symptom Management, 19, p. 125. Copyright 2000 by U.S. Cancer Pain Relief Committee. Adapted with permission.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9. Side Effects of Cancer Therapy

(1) Start antidiarrheal medications at the specified time. With


certain chemotherapeutic agents, antidiarrheal medication
should be provided so that patients can self-administer at
the onset.
(2) Avoid foods high in insoluble fiber (e.g., raw fruits and vegetables), greasy or fried foods, lactose, skins, seeds, legumes, caffeine, alcohol, and hyperosmotic liquids (Muehlbauer et al.,
2009). These may be stimulating or irritating to the GI tract.
(3) Include foods high in soluble fiber or pectin in their diets and
low insoluble fiber foods such as rice noodles, bananas, white
toast, skinned turkey or chicken, fish, and mashed potatoes
(Muehlbauer et al., 2009).
(4) Maintain fluid intake by drinking 810 large glasses each day of
clear fluids (e.g., bouillon; weak, tepid decaffeinated tea; gelatin; sports drinks). Water alone lacks the needed electrolytes
and vitamins. Carbonated and caffeinated drinks contain relatively few electrolytes and may worsen diarrhea. Fluids with glucose are useful because glucose absorption drives sodium and
water back into the body.
(5) Limit the use of sugar-free candies or gum made with sugar alcohol (sorbitol) (NCI, 2012a).
(6) Eat food at room temperature if not tolerated otherwise. Hot
and cold foods may aggravate diarrhea.
(7) Limit or avoid milk and dairy products.
(8) Avoid hyperosmotic supplements (e.g., Ensure), which can contribute to the production of loose, high-volume stools (Muehlbauer et al., 2009).
(9) Clean the rectal area with mild soap and water after each bowel
movement, rinsing well, and patting dry with a soft towel. Cleaning decreases the risk of infection and skin irritation.
(10) Apply moisture-barrier ointment to protect perianal skin.
(11) Take warm sitz baths to relieve pain related to perianal inflammation. Anesthetic creams or sprays may help to relieve pain
related to inflammation.
(12) Understand when diarrhea can be self-managed and when to
seek help.
(13) Report excessive thirst, fever, dizziness or light-headedness, palpitations, rectal spasms, excessive cramping, watery or bloody
stools, and continued diarrhea despite antidiarrheal treatment.
These symptoms can be life threatening.
3. Mucositis: Mucositis is a common complication of both systemic cytotoxic therapy and radiation therapy. Severe mucositis is reported in > 90%
of patients with head and neck cancer who are receiving concurrent chemotherapy and radiation (Sonis, 2011) and in the majority of patients
undergoing HSCT (Raber-Durlacher, Elad, & Barasch, 2010). It is associated with decreased QOL and increased risk of infections, hospitalizations, opioid use, parenteral nutrition, and dose reductions and delays
(Murphy, 2007; Rosenthal, 2007).
a) Definitions
(1) Mucositis: A general term referring to inflammation of any mucosal membranes, including the oral cavity
(2) Stomatitis or oral mucositis: Any inflammatory condition of oral
tissue including mucosa, dentition, periapices, and periodontium (Eilers & Million, 2011). Stomatitis includes oral infections.
(3) Alimentary tract mucositis: Inflammation and mucosal damage
occurring in the mouth (stomatitis) and extending the entire
length of the alimentary tract
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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

b) Pathophysiology: Oral mucositis traditionally has been attributed to


the direct effects of cytotoxic drugs or radiation on epithelial stem
cells. More recently, evidence has suggested that microvascular injury and connective tissue damage in the submucosa precede epithelial damage. Oral mucositis is now described as having five phases
(Sonis, 2011).
(1) Initiation: Stomatotoxic drugs and radiation therapy generate
reactive oxygen species that damage DNA, resulting in cell, tissue, and blood vessel damage in the mucosa.
(2) Upregulation and generation of messenger signals: Chemotherapy and radiation therapy activate nuclear factor-B
(NF-B). This results in upregulation of a large number of genes
and release of proinflammatory cytokines, such as TNF-alpha
(TNF-), IL-1 beta (IL-1), and IL-6. These and other cytokines
are responsible for tissue injury and apoptosis.
(3) Signaling and amplification: In addition to causing direct tissue damage, proinflammatory cytokines activate the production
of tissue-damaging TNF-, IL-1, and IL-6, and other cytokines
that alter mucosal tissues.
(4) Ulceration: Tissue injury in the oral mucosa appears as ulcers
that penetrate through the epithelium to the submucosa. Bacteria penetrate the submucosa and stimulate macrophage activity, which increases the release of proinflammatory cytokines.
Angiogenesis also is stimulated.
(5) Healing: Signals from extracellular tissues stimulate epithelial
proliferation until the mucosa returns to its normal thickness.
Tissues do not return completely to normal, however, placing
them at increased risk for future injury.
c) Incidence of oral mucositis
(1) Incidence varies based on type of chemotherapy, dose, and schedule. Radiation therapy directed at mucosa increases the risk,
and incidence varies depending on the dose, field, and whether chemotherapy is used concurrently. Overall, 30%100% of
patients treated for cancer will develop some degree of mucositis (Brown, 2011).
(2) HSCT recipients
(a) Up to a 100% risk
(b) Factors such as intensity of treatment regimen, transplant
type, and use of total body irradiation can affect incidence
(Raber-Durlacher et al., 2010).
(3) Incidence in patients undergoing head and neck radiation therapy is 65%90% (Sonis, 2011).
d) Risk factors
(1) Mucosal cells have a rapid mitotic rate and are susceptible to
chemotherapy and radiation (Raber-Durlacher et al., 2010).
The following classes of chemotherapy agents are associated
with mucositis.
(a) Antimetabolites: Increased risk noted with bolus delivery
of 5-FU
(b) Antitumor antibiotics
(c) Alkylating agents: Increased risk noted with high-dose melphalan
(d) Plant alkaloids
(e) Rapamycin (mTOR) inhibitors
(2) Biologic agents, particularly IL-2 and IFN
(3) Neutropenia
(4) Drugs or therapies that alter mucous membranes (Wujcik, 2014)
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9. Side Effects of Cancer Therapy

(a) Oxygen therapy: Dries out the mucosal lining


(b) Anticholinergics: Decrease salivary flow
(c) Phenytoin: Causes gingival hyperplasia
(d) Steroids: Can result in fungal overgrowth
(5) Total body irradiation or radiation therapy to the head or neck
(6) Dental disease and poor oral hygiene (Brown, 2011)
(7) Ill-fitting dentures: Irritate the mucosa and break integrity
(8) Advanced age and youth (Brown, 2011)
(a) Older adult patients may be at risk because of degenerative changes, decreased salivary flow, diminished keratinization of mucosa, and increased prevalence of gingivitis.
(b) Younger patients are prone to develop oral mucositis more
frequently than older patients because of their increased
rate of basal cell turnover (Treister & Woo, 2013).
(9) History of alcohol and tobacco use: Alcohol and tobacco irritate the mucosa. Tobacco affects microcirculation, which may
delay healing (Eilers & Million, 2011).
(10) Poor nutrition: Reduced nutritional intake delays healing.
(11) Consumption of irritating foods: Acidic or spicy foods may inflame and traumatize mucosa (Wujcik, 2014).
(12) Dehydration alters mucosal integrity.
(13) Patients with head and neck cancer are at especially high risk if
they have surgery followed by radiation therapy. Patients with
cancers of the mouth and oropharynx are at highest risk (>
90%) (Sonis, 2011).
(14) Leukemia, lymphoma, and HSCT put patients at risk because
treatment involves drugs with a great potential to produce oral
mucositis and cause prolonged neutropenia.
(15) Methotrexate for prophylaxis of GVHD following HSCT (Brennan, von Bltzingslwen, Schubert, & Keefe, 2006; Cutler et
al., 2005)
(16) Hepatic or renal impairment: Inadequate metabolism or excretion of certain mucotoxic cytotoxic agents
(17) Combined chemotherapy and radiation is associated with a
greater risk of mucositis (Eilers & Million, 2011).
e) Clinical manifestations
(1) The pattern of mucositis varies both by drug regimen and
by individual. Intensity and duration vary by type of drug,
dose, and frequency of administration (Raber-Durlacher et
al., 2010).
(a) Chemotherapy-induced oral mucositis develops most often four to seven days following standard-dose chemotherapy and peaks within two weeks (Raber-Durlacher et al.,
2010).
(b) HSCT recipients experience mucositis three to five days
following the conditioning regimen.
(c) Patients receiving head and neck radiation therapy experience mucositis during week two of therapy, and it can last
for weeks to months (Raber-Durlacher et al., 2010).
(2) Intensity increases with higher doses of cytotoxic drugs. Drugs
that are not usually stomatotoxic at standard doses (e.g., cyclophosphamide) can cause cellular damage to the mucosa at high
doses (Keefe et al., 2007).
(3) Signs and symptoms (Eilers & Million, 2011)
(a) Changes in taste and ability to swallow
(b) Hoarseness or decreased voice strength
(c) Pain when swallowing or talking
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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(d) Changes in the color of the oral mucosa (e.g., pallor, erythema of varying degrees, white patches, discolored lesions or ulcers)
(e) Changes in oral moisture (e.g., amount of saliva, quality
of secretions)
(f) Edema of oral mucosa and tongue
(g) Mucosal ulcerations
f) Assessment
(1) Use a standardized assessment tool or scale when performing a
physical examination. Scales designed for clinical use take into
account symptoms, signs, and functional disturbances associated with oral mucositis and assign an overall score. The following are three common tools.
(a) Oral Assessment Guide: This tool contains eight categories
that reflect oral health and function (Eilers, Berger, & Peterson, 1988) (see Table 27).
(b) WHO (1979)
(c) CTCAE: This tool consists of a 15 grading index that is associated with descriptions of oral mucosal changes (see Table 28) (NCI CTEP, 2010).
(2) After removing dental appliances, examine the outer lips, teeth,
gums, tongue, soft and hard palate, and buccal mucosa for color, moisture, integrity, and cleanliness (Brown, 2011).
(3) Assess for changes in taste, voice, ability to swallow, pain, and
discomfort.
(4) Examine the saliva for amount and quality.
g) Collaborative management: Currently, no standard of care exists for
the prevention and treatment of oral mucositis. MASCC, in collaboration with the International Society for Oral Oncology, issued clinical
practice guidelines in 2004 with suggestions and recommendations
based on literature published between 1966 and 2001. The guidelines
were revised in 2005 and again in 2007 (Keefe et al., 2007). ASCO has
published guidelines as well (Hensley et al., 2009).
(1) Oral care protocols, including patient education, should be instituted to reduce the severity of oral mucositis from chemotherapy and radiation therapy (Brown, 2011). Patient education may improve compliance with oral care, frequency, and
ability to cope with mucositis.
(a) Provide patient education, which is essential in promoting
good oral hygiene (Dodd, 2004).
(b) Benefits of oral care may include decreased risk of infection, decreased pain, and elevated microbial flora
(Brown, 2011).
(c) Conduct a pretreatment dental evaluation with attention
to potentially irritating teeth surfaces, underlying gingivitis, periodontal infection, and ill-fitting dentures. Crucial
dental work should be done before chemotherapy begins.
Removing braces may be necessary in adult and pediatric
patients if they are to undergo transplantation or if prolonged periods of neutropenia are anticipated.
(d) Emphasize intake of high-protein foods and increased fluid intake (> 1,500 ml/day).
(2) Prevention of oral mucositis (Keefe et al., 2007; Peterson et
al., 2012)
(a) Oral cryotherapy (ice chewing) is recommended for patients receiving bolus 5-FU for GI malignancies, bolus edatrexate, or high-dose melphalan.
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9. Side Effects of Cancer Therapy

217

Table 27. Oral Assessment Guide


Numeric and Descriptive Ratings
Category

Tools for
Assessment

Voice

Auditory

Converse with patient.

Normal

Deeper or raspy

Difficulty talking or
painful

Swallow

Observation

Ask patient to swallow.


To test gag reflex, gently place
blade on back of tongue and
depress.
Observe result.

Normal swallow

Some pain on swallowing

Unable to swallow

Lips

Visual/palpatory

Observe and feel tissue.

Smooth and pink


and moist

Dry or cracked

Ulcerated or bleeding

Tongue

Visual and/or
palpation

Feel and observe appearance


of tissue.

Pink and moist


and papillae
present

Coated or loss of papillae with a shiny


appearance with or
without redness

Blistered or cracked

Saliva

Tongue
blade

Insert blade into mouth, touching the center of the tongue


and the floor of the mouth.

Watery

Thick or ropy

Absent

Mucous
membranes

Visual

Observe appearance of tissue.

Pink and moist

Reddened or coated
(increased whiteness) without ulcerations

Ulcerations with or
without bleeding

Gingiva

Tongue
blade and visual

Gently press tissue with tip of


blade.

Pink, stippled,
and firm

Edematous with or
without redness

Spontaneous bleeding or bleeding with


pressure

Teeth or
dentures (or
denturebearing area)

Visual

Observe appearance of teeth


or denture-bearing area.

Clean and no debris

Plaque or debris in
localized areas
(between teeth if
present)

Plaque or debris
generalized along
gum line or denture-bearing area

Methods of Measurement

Note. Table courtesy of June Eilers, PhD, APRN-CNS, BC, The Nebraska Medical Center. Used with permission.

(b) Chlorhexidine is not recommended for treatment of mucositis (Harris, Eilers, Harriman, Cashavelly, & Maxwell, 2008;
Keefe et al., 2007; Worthington et al., 2011).
(c) Consider use of a keratinocyte growth factor to reduce the
severity and duration of oral mucositis in patients with hematologic malignancies undergoing high-dose chemotherapy and total body irradiation for autologous HSCT (Keefe
et al., 2007; Raber-Durlacher et al., 2013).
(3) Prevention of GI mucositis (Keefe et al., 2007)
(a) Either ranitidine or omeprazole is recommended for the
prevention of epigastric pain after treatment with cyclophosphamide, methotrexate and 5-FU, or 5-FU with or
without levcovorin.
(b) Amifostine has been suggested for reducing the severity
of esophagitis caused by the combination of chemotherapy and radiation therapy for non-small cell lung cancer (Keefe et al., 2007). However, ASCO does not recommend the routine use of amifostine for the prevention of
esophagitis in patients receiving concurrent chemotherapy because of insufficient evidence (Hensley et al., 2009).
In a 2011 Cochrane review, amifostine was found to have
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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Table 28. National Cancer Institutes Common Terminology Criteria


for Adverse Events: Oral Mucositis
Grade

Description

Asymptomatic or mild symptoms; intervention not indicated

Moderate pain, not interfering with oral intake; modified diet indicated

Severe pain, interfering with oral intake

Life-threatening consequences; urgent intervention required

Death

Note. From Common Terminology Criteria for Adverse Events [v.4.03], by the National Cancer Institute Cancer
Therapy Evaluation Program, 2010. Retrieved from http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010
-06-14_QuickReference_8.5x11.pdf.

weak evidence of benefit for prevention of any mucositis


(Worthington et al., 2011).
(c) Other agents that have been studied include sucralfate,
aloe vera, glutamine, G-CSF, honey, and antibiotic lozenges
containing polymyxin, tobramycin, and amphotericin. Evidence of benefit was weak in small studies that included these
agents. Further study is required (Worthington et al., 2011).
(d) Low-level laser therapy is recommended for the prevention
of oral mucositis in adult patients receiving HSCT conditioned with high-dose chemotherapy with or without total
body irradiation. It is also recommended for patients with
head and neck cancer undergoing radiation without concurrent chemotherapy (Migliorati et al., 2013).
(4) Treatment: Currently, no evidence-based recommendations exist for the treatment of established oral mucositis. Interventions
are aimed at symptom relief and preventing further tissue damage. These interventions may include the following (Harris et
al., 2008; Keefe et al., 2007).
(a) Encourage the use of oral agents to promote cleansing,
moisture, and comfort (see Table 29).
(b) Encourage patients to brush, floss, and rinse to maintain
mucosal health.
(c) Administer systemic pain medications for mucositis pain.
MASCC guidelines recommend the use of patient-controlled
analgesia in HSCT recipients experiencing oral mucositis
pain (Keefe et al., 2007).
(d) Culture mucosal lesions so that appropriate antimicrobial
agents can be prescribed. Candidal lesions look like whitish or cream-colored plaques on the mucosa and often are
treated while cultures are pending.
h) Patient and family education: Stress the goals of keeping the oral cavity clean, moist, and intact to prevent further damage to the mucosa during mucotoxic therapy (Harris et al., 2008; Keefe et al., 2007).
To do this, patients should
(1) Perform a daily oral self-examination, and report signs and
symptoms of mucositis.
(2) Comply with an oral hygiene program. Oral hygiene should be
performed after every meal and at bedtime. If mild to moderate
dysfunction is present, the frequency of oral hygiene should be
increased to every two to four hours. If the condition progresses to a more severe dysfunction, hourly care may be indicated.
The program should include the following.
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Chapter 9. Side Effects of Cancer Therapy

219

Table 29. Commonly Used Agents for Mucositis Management


Agent

Efficacy

Comments

Bland rinses
0.9% saline
solution

Formal evaluation is lacking.

Inexpensive rinsing solution

Sodium bicarbonate

Formal evaluation is lacking.

Creates an alkaline environment that promotes bacterial microflora


Unpleasant taste may affect adherence.
Recommended by NCI

0.9% saline/sodium bicarbonate

Formal evaluation is lacking.

Inexpensive rinsing solution


teaspoon salt mixed with 2 tablespoons sodium bicarbonate with 32 ounces of water
Unpleasant taste may affect adherence.
Recommended by NCI

Rinse, multiagent

Data demonstrating efficacy are lacking for prevention


and treatment of mucositis.

Various agents include antihistamines, lidocaine, and


Mylanta.
Agents may be useful for pain or discomfort only.
Patients may experience numbness, which can cause
potential injury.
Alcohol-based elixirs should be avoided.
Discontinue if patient experiences discomfort related
to rinse (e.g., nausea and vomiting)

Coating agents, mucosal protectants


Sucralfate
suspension

Most data demonstrate no statistically significant difference in oral mucositis severity, pain intensity scores,
and other subjective symptoms (e.g., taste alteration, dry mouth). Not recommended for practice (Harris et al., 2008). A Cochrane review published in 2011
found that some benefit may exist for the reduction of
oral mucositis. Further studies are needed (Worthington et al., 2011).

Mucosal coating agent


Poor tolerability and potential for GI side effects (e.g.,
nausea and rectal bleeding) (Harris et al., 2008)

Gelclair

Bioadherant oral gel forms a coating to make a barrier.


Provides moisture and is flavorful
Not recommended for prevention or treatment of oral
mucositis

May be helpful for improvement of swallowing and


pain scores

MuGard

Mucoadhesive oral wound rinse that forms a protective coating over the oral mucosa. Indicated for the
management of mucositis/stomatitis (which may be
caused by radiation therapy or chemotherapy) and all
types of oral wounds.

Dose is 5 ml. Rinse in mouth for at least 1 minute.


Coat entire oral cavity. If necessary, up to 10 ml may
be used to coat entire oral cavity.

Recommended for reduction of esophagitis induced by


simultaneous chemotherapy and radiation therapy in
patients with non-small cell lung cancer (Keefe et al.,
2007). However, ASCO does not recommend the routine use of amifostine for the prevention of esophagitis in patients receiving concurrent chemotherapy because of insufficient evidence (Hensley et al., 2009).

Tissue protector
Studies needed to determine role in prevention of oral
mucositis

Overall, data demonstrate no significant change in


oral mucositis severity or suppression of any type of
oral microflora. A 2011 Cochrane review found no
benefit over placebo for the prevention of mucositis
(Worthington et al., 2011).

Contains alcohol
Reports of rinse-induced discomfort, taste alteration
Not recommended for oral mucositis (Keefe et al.,
2007)
Can turn teeth brown

Tissue protectants
Amifostine

Antiseptic agents
Chlorhexidine

(Continued on next page)

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220

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

Table 29. Commonly Used Agents for Mucositis Management (Continued)


Agent

Efficacy

Comments

Hydrogen
peroxide

Mixed results: Linked to exacerbation or dryness, stinging, pain, and nausea; some reports of intensification
of symptoms as a result of glossodynia (burning sensation)

Repeated use as a rinse is not recommended; longterm use is discouraged.


At full potency, it may break down new granulation tissue and disrupt normal oral flora due to damage of
fibroblasts and keratinocytes.

Povidone-iodine

Possesses antiviral, antibacterial, and antifungal efficacy; less tolerable than normal saline
No evidence that this agent is more effective than placebo (Worthington et al., 2011)

Potency limits use in patients with new granulation tissue. Swallowing is contraindicated.

Antimicrobial agents
Acyclovir (and its
analogs)

Antiviral
Not recommended for prevention of oral mucositis

Antimicrobial
lozenges

Not recommended for prevention of radiation-induced


oral mucositis

More research is needed.

Anti-inflammatory agents
Kamillosan liquid
rinse

Unfavorable results in clinical trials

Most patients appear to develop mucositis despite


treatment.

Chamomile

Lacks data demonstrating its efficacy

Anti-inflammatory, antipeptic properties reported


Inexpensive, readily available, and innocuous

Oral corticosteroids

No significant difference in degree of mucositis compared to placebo

Data are limited; definitive conclusions cannot be


drawn.

Benzydamine

Nonsteroidal anti-inflammatory analgesic


Antitumor necrosis factor activity

Only recommended for the prevention of oral mucositis in patients with solid tumors of the head and
neck receiving radiation therapy (Keefe et al., 2007).
In a 2011 Cochrane review, this agent was found to
have weak, unreliable evidence for the reduction of
mucositis (Worthington et al., 2011).

Topical lidocaine

Limited data; may provide significant relief of limited duration

Requires frequent application; may lead to decreased


sensitivity and additional trauma and impair taste
perception
Prophylaxis is not recommended.

Topical capsaicin

Pilot data demonstrated marked reduction in oral pain.

Clinical potential possibly linked to reepithelialization


and elevation of pain threshold
Further study is warranted.

Morphine

Topical morphine has limited utility. Patient-controlled


analgesia using morphine is recommended for patients undergoing HSCT.

Oral alcohol-based formulations may cause burning.


Comprehensive pain assessments should be performed to adequately treat pain associated with mucositis.

Analgesics

Antiproliferative, mucosal protectant, cytokine-like agents and growth factors


GM-CSF

Some data indicate reduction in oral mucositis severity


and pain; others do not.
No evidence of benefit with duration or severity of oral
mucositis (Worthington et al., 2011)

Oral mouthwashes are not recommended.


High rate of drug discontinuation because of intolerable side effects, including local skin reaction, fever,
bone pain, and nausea when administered subcutaneously.

G-CSF

Weak, unreliable evidence of benefit for prevention of


mucositis (Worthington et al., 2011)

Further study is needed to draw any conclusion.

(Continued on next page)

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Chapter 9. Side Effects of Cancer Therapy

221

Table 29. Commonly Used Agents for Mucositis Management (Continued)


Agent
Keratinocyte
growth factor-1:
Palifermin

Efficacy

Comments

Approved for prevention of oral mucositis in patients undergoing autologous HSCT receiving high-dose chemotherapy or total body irradiation

60 mcg/kg/day IV for 3 days prior to the preparatory


regimen and for 3 days post-transplant
Further study is needed in other patient populations.

Cryotherapy (ice
chips)

Demonstrates consistent reduction in incidence and severity of oral mucositis among patients receiving bolus 5-FU
Also recommended for bolus edatrexate chemotherapy
infusion and high-dose melphalan infusions in HSCT

Not recommended in patients with head and neck


cancers
Apply ice chips to mouth 5 minutes before bolus 5-FU
therapy and continue for 30 minutes after (Peterson
et al., 2012).
Not recommended in patients receiving capecitabine
or oxaliplatin because of potential discomfort with
exposure to coldness (Harris et al., 2008)

L-Glutamine

Essential amino acid, poorly absorbed


Not recommended systemically for prevention of GI mucositis

Has not been shown to prevent mucositis


IV formulation under investigation

Other

ASCOAmerican Society of Clinical Oncology; 5-FU5-fluorouracil; G-CSFgranulocytecolony-stimulating factor; GIgastrointestinal; GM-CSFgranulocyte macrophagecolony-stimulating factor; HSCThematopoietic stem cell transplantation; IVintravenous; NCINational Cancer Institute
Note. Based on information from Bensinger et al., 2008; Brown, 2011; Harris et al., 2008; National Cancer Institute, 2012b; Peterson et al., 2013; RaberDurlacher et al., 2013; Worthington et al., 2011.
From Nursing Interventions and Supportive Care for the Prevention and Treatment of Oral Mucositis Associated With Cancer Treatment, by J. Eilers, 2004,
Oncology Nursing Forum, 31(Suppl. 4), pp. 1920. Copyright 2004 by the Oncology Nursing Society. Adapted with permission.

(a) Floss the teeth with dental tape at least once daily or as advised by the clinician (Harris et al., 2008). However, patients
who do not regularly floss should not do so while immunosuppressed (Eilers & Million, 2011).
(b) Brush all tooth surfaces with a soft toothbrush for at least
90 seconds at least twice daily. Allow toothbrush to air dry
before storing, and replace toothbrush frequently (Harris et al., 2008). Sponge swabs are not as effective as toothbrushes and should be avoided when cleaning the teeth except in patients who cannot tolerate a toothbrush because
of severe pain with mucositis. However, sponge swabs may
be beneficial for cleaning the mucous membranes of the
oral cavity (Eilers & Million, 2011).
(c) Cleanse the oral cavity after meals, at bedtime, and at other times by vigorously swishing the mouth with an appropriate cleansing rinse (see Table 29). Oral rinsing should
be done to remove excess debris, hydrate the oral mucosa,
and aid in the removal of organisms (Eilers & Million, 2011;
Harris et al., 2008). Patients should use one tablespoon of
rinse to swish in the oral cavity for 30 seconds and then expectorate (Harris et al., 2008).
(d) Apply water-based moisturizers to lips.
(e) Maintain hydration
(f) Consider the use of oral moisturizers to promote comfort
if xerostomia exists (Eilers & Million, 2011).
(g) Avoid irritating agents, including commercial mouthwashes containing phenol, astringents, or alcohol; highly abrasive toothpastes; acidic, hot, or spicy foods and beverages; rough foods; alcohol; tobacco; poorly fitting dentures;
braces; and lemon-glycerin swabs and solutions (Harris
et al., 2008).
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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(h) Recommendations for patients with dentures (NCI,


2012b)
i. Clean dentures twice a day and rinse them well.
ii. Soak dentures in an antibacterial solution when they
are not being worn.
iii. Clean denture soaking cups and change soaking solution daily.
iv. Remove dentures and other oral devices when cleaning the mouth. If mouth sores are present, or if the
mouth is inflamed or painful, avoid using removable
oral devices to prevent further irritation.
(i) Instruct patients to report pain associated with mucositis.
Treat pain with oral topical agents or systemic opioids or
nonopioids. Avoid oral topical agents that contain alcohol
(Eilers & Million, 2011).
4. Anorexia
a) Definitions
(1) Anorexia: Loss of a desire to eat (NCI, n.d.) (see Table 30)
(2) Cachexia: Cancer cachexia is defined as a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass
(with or without loss of fat mass) that cannot be fully reversed
by conventional nutritional support and leads to progressive
functional impairment. The pathophysiology is characterized
by a negative protein and energy balance driven by a variable
combination of reduced food intake and abnormal metabolism (Fearon et al., 2011, p. 490) (see Figure 26).
b) Pathophysiology
(1) The two entities are interrelated. Lack of food intake is only
one factor that contributes to weight loss, muscle wasting, and
malnutrition.
(2) Anorexia/cachexia results from a complicated process involving numerous physiologic and psychological factors.
(a) Tumor effect (Inui, 2002)
i. Obstruction of the GI tract can lead to nutrient malabsorption, nausea, vomiting, and pain.
ii. Proinflammatory cytokines such as IL-6, IL-1, TNF-,
and IFN alfa may be released by the tumor and cause
satiety and metabolic abnormalities. These agents may
serve as tumor promoters and contribute to a negative
prognosis (MacDonald, 2007; Tisdale, 2010).
Table 30. National Cancer Institutes Common Terminology Criteria
for Adverse Events: Anorexia
Grade

Description

Loss of appetite without alteration in eating habits

Oral intake altered without significant weight loss or malnutrition; oral nutritional
supplements indicated

Associated with significant weight loss or malnutrition (e.g., inadequate oral caloric
and/or fluid intake); tube feeding or total parenteral nutrition indicated

Life-threatening consequences; urgent intervention indicated

Death

Note. From Common Terminology Criteria for Adverse Events [v.4.03], by the National Cancer Institute
Cancer Therapy Evaluation Program, 2010. Retrieved from http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03
_2010-06-14_QuickReference_8.5x11.pdf.

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9. Side Effects of Cancer Therapy

Figure 26. Cancer Cachexia


Diagnostic Criteria
Weight loss > 5% over the past 6 months; or
Body mass index < 20 and any degree of weight loss > 2%
Appendicular skeletal muscle index consistent with sarcopenia (another wasting syndrome)
and weight loss of > 2%
Stages of Cancer Cachexia
Precachexia: Weight loss of < 5%, along with other symptoms such as impaired glucose tolerance or anorexia
Cachexia: Weight loss > 5% or other symptoms and conditions consistent with the diagnostic criteria for cachexia
Refractory cachexia: Patients experiencing cachexia who are no longer responsive to cancer
treatment, have a low performance score, and have a life expectancy of < 3 months
Note. Based on information from Fearon et al., 2011.

iii. Metabolic abnormalities may lead to elevated blood


glucose, amino acid, and free fatty acid levels, resulting in early satiety and appetite suppression.
iv. Neurohormonal abnormalities may directly affect the
hypothalamic appetite center.
v. Hypercalcemia secondary to bony involvement or
paraneoplastic syndrome may lead to nausea, vomiting, and anorexia.
(b) Treatment effects (Cunningham & Huhmann, 2011)
i. Surgery may result in malabsorption, obstruction, and
fluid and electrolyte abnormalities.
ii. Chemotherapy and radiation therapy side effects include nausea, vomiting, mucositis, taste changes, xerostomia, constipation, and diarrhea.
iii. Combination therapy results in a greater number of
adverse effects.
(c) Psychosocial effects
i. Cancer-related depression often coexists with anorexia and cachexia, especially with patients who
are at a late stage or have multiple symptoms (Jimnez et al., 2011).
ii. The prevalence of depression among patients with
cancer is estimated to be 10%30%, compared to
5%10% in the general medical population (Illman
et al., 2005).
iii. Anxiety, fear, grief, fatigue, pain, and the patients
reaction to body image changes may contribute to
anorexia.
(3) Cachexia results in decreased survival and adherence to chemotherapy and increased treatment toxicity (Blum & Strasser, 2011).
c) Incidence: Historical data demonstrated an overall incidence of anorexia/cachexia in patients with cancer of 50%, increasing to 80%
before death (Inui, 2002).
d) Risk factors (Cunningham & Huhmann, 2011; Del Fabbro, Dalal, &
Bruera, 2006)
(1) Advanced cancer
(2) Solid tumor: Most common types are head and neck, GI, and lung.
(3) Chronic illness such as pulmonary disease and congestive heart
failure
(4) Increased prevalence in the very young and older adults
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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

(5) Surgery, radiation, chemotherapy, biotherapy, and targeted


therapies
(6) Multimodal therapies
e) Clinical manifestations (Cunningham & Huhmann, 2011; Strasser
& Bruera, 2002)
(1) Involuntary weight loss of > 5% of usual weight
(2) Changes in appetite
(a) Changes in taste and smell
(b) Early satiety
(3) Changes in GI tract function
(a) Dysmotility
(b) Inactivation of bile salts or pancreatic enzymes
(c) Partial or complete obstruction
(4) Loss of muscle mass
(5) Loss of adipose tissue
(6) Fatigue and weakness
(7) Immune system impairment
(8) Metabolic dysfunction
(9) Hypoalbuminemia
f) Assessment
(1) Monitor weight: Compare with pretreatment weight.
(2) Obtain a diet history or have patient complete a food diary for
several days.
(3) Measure body composition.
(a) Triceps skinfold thickness estimates body fat.
(b) Mid-arm muscle circumference estimates muscle mass.
(4) Laboratory results
(a) Laboratory tests generally are nonspecific for malnutrition
(Cunningham & Huhmann, 2011). The practitioner will
evaluate patient labs for the presence of contributing factors that may be corrected.
(b) Assess for endocrine abnormalities (e.g., thyroid dysfunction, metabolic abnormalities, hypogonadism) (NCCN,
2013e).
(5) Assess functional status (Chang, Xia, & Kasimis, 2005; Ottery,
1994).
(a) The Patient-Generated Subjective Global Assessment and
the Functional Assessment of Anorexia/Cachexia Therapy are easy-to-use tools that patients complete in the clinical setting.
(b) Functional status tools include symptom distress and QOL
questions.
(c) Validated cachexia assessment tools based on updated definitions are being investigated (Blum & Strasser, 2011).
g) Collaborative management: The extent of nutrition intervention depends on the cause of weight loss and overall goals of the patient,
family, and healthcare team.
(1) Treatment of the cancer is the primary objective.
(2) Symptom management: Management of symptoms such as n/v,
mucositis, oral candidiasis, diarrhea, constipation, taste changes, dysphagia, xerostomia, fatigue, pain, and depression may
improve anorexia. (See the discussion of management in the
specific sections of this publication.)
(3) Pharmacologic intervention: Progestins and corticosteroids are
the only two classes of drugs to have demonstrated effectiveness as appetite stimulants (Adams et al., 2009; NCCN, 2013e).
(a) Progestins (Berenstein & Ortiz, 2012; Dy & Apostol, 2010)
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Chapter 9. Side Effects of Cancer Therapy

i. Megestrol acetate is most commonly used.


ii. Improves appetite and weight gain in patients with
cancer; however, it does not improve QOL.
iii. Mechanism of action is not well established.
iv. Optimal dose is not defined but ranges from 100
1,600 mg/day.
v. Side effects include deep vein thrombosis, edema, impotence in men, and GI disturbances.
(b) Corticosteroids (Adams et al., 2009; NCCN, 2013e)
i. Mechanism of action is unknown but may be related
to euphoric and anti-inflammatory effects.
ii. Effects are short-lived.
iii. Many side effects, both short and long term, can occur, including immunosuppression, hyperglycemia,
and muscle wasting.
(4) Nonpharmacologic interventions (Adams et al., 2009; NCCN,
2013e)
(a) Interventions may not increase weight or length of survival but may improve QOL.
(b) Refer to a dietitian for nutritional counseling. This has been
shown to improve dietary intake.
(c) Provide high-calorie/high-protein oral supplements as
needed and tolerated.
(d) Enteral or parenteral nutrition: Consider if the disease or
treatment interferes with the patients ability to eat or to
absorb nutrients (NCCN, 2013e).
i. Enteral: Patients must have a functioning bowel. Complications include aspiration pneumonia, electrolyte
abnormalities, diarrhea, and infection.
ii. Parenteral: Includes central parenteral nutrition,
which requires a central VAD, and peripheral parenteral nutrition. Complications include high infection rate.
h) Patient education
(1) Provide written handouts, stressing high-calorie/high-protein
foods.
(2) Monitor and record weight weekly, using the same scale at the
same time of the day.
(3) Encourage small, frequent meals.
(4) Provide an attractive setting for meals.
(5) Encourage physical activity.
(6) Use measures to control n/v, mucositis, dry mouth, taste changes, and other side effects of treatment.
(7) Include patients in family activities to avoid isolation, even if patients have no appetite. Do not force patients to eat.
(8) Remind families that patients lack of appetite is caused by the
effects of the disease and treatment and is not their fault.
(9) Refer to community resources as needed, such as home care
and Meals on Wheels.
(10) Refer patients for psychosocial interventions and emotional
support.
5. Constipation
a) Definition: Excessively hard, dry bowel movements that are infrequent and a result of decreased rectal emptying or filling (CampSorrell, 2011). Constipation may be a presenting symptom of the
cancer diagnosis, a side effect of therapy, the result of tumor progression, or unrelated to the cancer or therapy. Depression and
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

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Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (Fourth Edition)

anxiety caused by cancer treatment or pain can lead to constipation, either alone or with other functional and physiologic disorders. The most common causes are inadequate fluid intake and use
of pain medications.
b) Pathophysiology: Infrequent and difficult bowel evacuation, which
can be associated with abdominal bloating, pain, and discomfort. Decreases in fluid and fiber intake and in exercise/activity contribute to
the severity of constipation (Connolly & Larkin, 2012).
(1) Common contributing factors include advanced age, autonomic nervous system dysfunction, spinal cord compression from
tumor, metabolic effects, dehydration, immobility, cancer treatment, and medications such as opioids and tricyclic antidepressants (Woolery et al., 2008).
(2) Certain chemotherapy agents that cause n/v may contribute
to constipation, as n/v may result in decreased oral intake or
slowed peristaltic movement in the GI tract. In the absence of
food intake, fewer stools are produced, transit time increases,
and the stool becomes hard and difficult to eliminate.
(a) Agents that decrease motility include vinca alkaloids. Autonomic nervous system dysfunction can result in upper
colon impaction, colicky abdominal pain, and paralytic ileus. Rectal emptying is decreased when nonfunctional afferent and efferent pathways from the sacral cord are interrupted (Camp-Sorrell, 2011).
(b) Vincristine, vinorelbine, and vinblastine can cause neurotoxicity that affects the smooth muscles of the GI tract, leading to decreased peristalsis or paralytic ileus.
(c) Vincristine may damage the mesenteric plexus of the colon.
(3) Opioids profoundly affect the bowels ability to maintain appropriate motility. They are the primary cause of medicationinduced constipation (Bohnenkamp & LeBaron, 2010).
c) Incidence
(1) Clinically, constipation is a common problem for patients with
cancer occuring in 50%95% of patients. Patients receiving opioids are at highest risk (Woolery et al., 2008).
(2) Constipation has been reported in 20%35% of patients receiving vinblastine, especially in high doses or after prolonged
treatment (Engelking, 2008).
(3) Constipation, abdominal pain, and paralytic ileus are common
side effects of vincristine (Chu & DeVita, 2012).
(4) Vinorelbine may cause severe constipation, with an overall incidence of all grades of 35% (Sagent Pharmaceuticals, 2009).
(5) Constipation occurs in up to 55% of patients receiving thalidomide (Celgene Corp., 2013b) and approximately 38% of patients receiving lenalidomide (Celgene Corp., 2013a).
(6) Bortezomib causes constipation in 42% of patients (Millennium Pharmaceuticals, 2012).
d) Clinical consequences
(1) Abdominal or rectal discomfort or pain
(2) Nausea and/or vomiting
(3) Anorexia
(4) Impaction/obstruction
(5) Ileus
(6) Anal fissures
(7) Hemorrhoids
(8) Ruptured bowel and life-threatening sepsis
e) Risk factors (Woolery et al., 2008)
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Chapter 9. Side Effects of Cancer Therapy

(1) Advanced age


(2) Mechanical pressure on the bowel (e.g., bowel obstruction secondary to tumor in the GI tract, pressure from ascites)
(3) Damage to the spinal cord from T8 to L3, which causes compression of nerves that innervate the bowel
(4) Decreased mobility
(5) Dehydration
(6) Poor nutritional intake
(7) Low dietary fiber intake
(8) Metabolic and endocrine disorders
(a) Hypercalcemia
(b) Hypothyroidism
(c) Hypokalemia
(d) Diabetes mellitus
(9) Use of certain medications (Woolery et al., 2008)
(a) Neurotoxic chemotherapy drugs
(b) Anticholinergic medications
(c) Diuretics
(d) Opioids
(e) Aluminum- and calcium-based antacids
(f) Calcium and iron supplements
(g) Tricyclic antidepressants
(h) Antihypertensives
(i) Antispasmodics
(j) 5-HT3 antagonists
(k) NSAIDs
(l) Barbiturates
(10) Overuse of laxatives
f) Assessment
(1) Assess patterns of elimination, including the amount and frequency of elimination and the urge to defecate, character and
volume of the stool, and use of laxatives, stool softeners, or
other measures to enhance bowel function. Note that small
amounts of loose stool may indicate constipation as the liquid
stool passes around a stool mass. Small, pellet-like stool indicates slow colonic transit time, and long, thin pieces of stool
may indicate stenosis or hemorrhoids (Bohnenkamp & LeBaron, 2010).
(2) Assess patients usual dietary patterns, focusing on fluid and fiber intake.
(3) Assess mobility, activity level, and functional status.
(4) Assess for abdominal pain, distention, and presence or absence
of bowel sounds.
(5) Assess for the presence of straining, rectal pressure, excessive
flatulence, or cramping.
(6) Determine facts about the patients last bowel movement (e.g.,
when it occurred, amount, consistency, color, presence of blood).
(7) Determine current medication usage.
(8) Use laboratory results to assist in metabolic evaluation.
(9) Perform abdominal palpation and rectal examination if appropriate. A rectal examination is not routinely performed in pediatric patients. Rectal or stoma manipulation for examinations,
enemas, or suppositories should be avoided in myelosuppressed
patients because of the risk for bleeding, fissures, or abscesses
(NCI, 2012a; Woolery et al., 2008).
(10) Use radiographic imaging to differentiate between mechanical
obstruction and decreased motility from an ileus.
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g) Collaborative management: No evidence has shown any one laxative to be more efficacious than another (Woolery et al., 2008). The
cause of the constipation should be considered prior to beginning
treatment. NCCN (2013e) palliative care guidelines offer guidance
for the treatment of constipation.
(1) Pharmacologic interventions
(a) Bulk-forming laxatives (e.g., methylcellulose, psyllium,
calcium polycarbophil): Cause water to be retained in the
stool. Must be taken with at least 200300 ml of water to
avoid intestinal obstruction and are of limited use in patients who cannot tolerate fluids (Bohnenkamp & LeBaron, 2010; Woolery et al., 2008). Side effects include flatulence, abdominal distention and bloating, mechanical obstruction, and anaphylactic reactions (Woolery et al., 2008).
(b) Lubricant laxatives (e.g., mineral oil, glycerin suppositories): Coat and soften the stool. Excessive doses can lead
to malabsorption of fat-soluble vitamins and rectal seepage with perianal irritation (Bohnenkamp & LeBaron,
2010).
(c) Saline laxatives (e.g., magnesium salts, sodium phosphate):
Contain magnesium or sulfate ions. Act by drawing water
into the gut. Are of little use in a daily prevention program
and are used most often for acute evacuation of the bowel. Hypermagnesemia or hyperphosphatemia can occur
with renal insufficiency (Bohnenkamp & LeBaron, 2010).
(d) Osmotic laxatives (e.g., lactulose, sorbitol, polyethylene glycol [PEG]): Attract and retain water in the bowel, resulting
in softer stool. Side effects include abdominal pain, distention, and gas (Bohnenkamp & LeBaron, 2010).
(e) PEG with or without electrolytes is considered a hyperosmotic laxative and increases the water content of stool.
NCCN (2013e) recommends PEG for persistent constipation. Woolery et al. (2008) recommended that electrolytes not be administered with PEG when kidney function
is compromised.
(f) Detergent laxatives (e.g., docusate sodium): Have a direct
action on the intestines by allowing water and fats to penetrate into dry stool and decreasing electrolyte and water
absorption from the colon. Appropriate for short-term use
when straining is to be avoided.
(g) Stimulant laxatives (e.g., bisacodyl, senna): Act directly on
the colon to stimulate motility and are activated by bacterial degradation in the intestine. Most commonly used in a
prophylactic plan. Side effects include abdominal discomfort, electrolyte abnormalities, and hepatotoxicity (Woolery et al., 2008).
(h) Suppositories: Stimulate the intestinal nerve plexus and
cause rectal emptying. Not indicated for long-term bowel management.
(i) Prokinetic agents (e.g., metoclopramide, 1020 mg by
mouth every six hours): Promotes motility in the upper
GI tract and hastens gastric emptying and intestinal transit time. Exhibits antiemetic properties, which are the result of central and peripheral dopamine receptor inhibition. Doses are higher when used for CINV (Micromedex,
2013). Consider adding a prokinetic agent for constipation that is not associated with obstruction (NCCN, 2013e).
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9. Side Effects of Cancer Therapy

(j) Methylnaltrexone is approved for opioid-induced constipation in patients with advanced illness who are receiving
palliative care. It is a peripherally acting opioid receptor
antagonist that has shown efficacy in preventing opioidinduced constipation without diminishing pain, palliation,
or precipitating opioid withdrawal. Dosing is 0.15 mg/kg SC
every other day, not more often than once a day (NCCN,
2013e). Most common adverse effects reported were flatulence, abdominal pain, dizziness, diarrhea, nausea, and
hyperhidrosis. This drug is contraindicated with known or
suspected mechanical GI obstruction (Salix Pharmaceuticals, Inc., 2012).
(k) Use a combination laxative-stool softener prophylactically for patients receiving vinca alkaloids (Engelking, 2008).
(2) Other
(a) Include increased physical activity or passive exercise as appropriate in a bowel retraining regimen. This promotes the
urge to defecate by helping to move feces into the rectum.
(b) Help patients to maintain usual bowel habits during hospitalization. Provide privacy and comfort. Avoid use of a bedpan when constipation exists.
(c) Increase fluid and fiber intake and obtain a nutritional consult (Woolery et al., 2008).
(d) Begin management with oral medications.
(e) Rotating opioids may decrease constipation (e.g., switching
from a long-acting oral morphine to a transdermal fentanyl patch) (Woolery et al., 2008).
(f) Patient and family education
i. Increase fluid intake: Encourage patients to drink at
least eight 8-oz glasses of fluid daily unless medically contraindicated. Drinking warm or hot liquids before a defecation attempt may help to stimulate bowel movement (Woolery et al., 2008).
ii. Increase fiber in diet: Fiber causes feces to pass through
intestines more rapidly and decreases the occurrence
of fecal impaction.
High-fiber foods include 100% whole-grain cereals, breads, and bran; fruits such as prunes, peaches, apples, raisins, and dates; and vegetables such as
squash, broccoli, carrots, and celery (NCI, 2012a).
Advise patients that they may experience abdominal
discomfort, flatulence, or a change in bowel habits
in the first few weeks after increasing fiber intake.
Fiber tolerance will develop, and such effects can
be minimized by slowly titrating fiber consumption.
Adults should consume 2530 g/day total if tolerated (NCI, 2012a). This approach is contraindicated in patients who are at risk for bowel obstruction
(NCI, 2012a).
Fiber should not be recommended in patients with
cancer who have inadequate fluid intake (NCI,
2012a).
(3) Encourage patients to exercise regularly. Regular exercise stimulates GI motility.
(4) Teach diaphragmatic breathing and abdominal muscle exercises; these help to increase muscle tone, which assists with defecation (Engelking, 2008).
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(5) Help patients to develop a regular bowel program.


(6) Instruct patients to report constipation and to be aware of the
complications associated with constipation, such as fecal impaction.
(7) Stress that patients should call a physician to initiate a bowel
program if three days pass without a bowel movement.
(8) Ensure that all patients who are prescribed opioids are started
on pharmacologic and nonpharmacologic interventions to prevent constipation and maintain bowel program until opioids are
discontinued (Bohnenkamp & LeBaron, 2010).
6. Perirectal cellulitis
a) Definition: Inflammation and edema of the perineal and rectal area
b) Pathophysiology
(1) Minimal tears of the anorectal mucosa allow infection. The
most common anaerobic organisms include Bacteroides fragilis,
Peptostreptococcus, Prevotella, Fusobacterium, Porphyromonas, and
Clostridium. The most common aerobic bacteria include Staphylococcus aureus, Streptococcus, and Escherichia coli. Communityacquired methicillin-resistant Staphylococcus aureus (known as
MRSA) has been implicated in rectal abscess infections (Valesky
& Kifaieh, 2012).
(2) Infection starting as a local abscess can lead to systemic sepsis.
c) Incidence: Overall incidence has decreased in the past decade, presumably because of the early use of empiric antibiotics in febrile neutropenic patients. Perirectal abscesses are more common in patients
with anorectal cancer or hematologic malignancies and may be present at initial diagnosis (Valesky & Kifaieh, 2012).
d) Risk factors
(1) Chronic neutropenia or thrombocytopenia
(2) Constipation: The passage of hard stool causes trauma to the
rectal mucosa.
(3) Diarrhea: Caustic fluid irritates and breaks down perirectal tissue.
(4) Perirectal mucositis caused by chemotherapy and/or radiation therapy
(5) Any rectal trauma, such as rectal stimulation or the use of rectal thermometers, enemas, or suppositories
(6) Hemorrhoids or anal fissures/abscesses
e) Assessment
(1) Ask patients if they are experiencing perineal and/or rectal discomfort. Fear of defecation related to pain may not be reported and may increase risk of constipation. A large majority of patients with anal abscess will complain of dull, aching, or throbbing pain, which may worsen when sitting or before defecation.
(2) Monitor for the presence of fever.
(3) Perform a physical examination of the perineal area. The entrance site for the infective agent may be a small tear that shows
minimal irritation. Conversely, localized tenderness, gross swelling, fluctuance, erythema, and drainage may be observed if an
abscess is present. An abscess of the perirectal area may produce bloody, purulent, or mucoid drainage. Obtain a culture,
if possible, for identification of infectious organisms (Valesky
& Kifaieh, 2012).
(4) Consider abdominal/pelvic CT (NCCN, 2013f) if an abscess
is suspected. MRI and ultrasound are also used for diagnosis
of an abscess. Look for and document tissue sloughing and
necrosis.
f) Collaborative management (NCCN, 2013f)
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chapter 9. Side Effects of Cancer Therapy

(1) Ensure that antibiotic coverage includes a specific antianaerobic


agent in addition to broad-spectrum aerobic coverage. Consider
Enterococcus or Candida coverage if appropriate (NCCN, 2013f).
(2) Administer antipyretic medications to relieve fever.
(3) Teach and encourage patients to take sitz baths or use gentle
external perineal irrigation.
(4) Administer stool softeners, and encourage patients to eat a lowbulk diet. Consult a dietitian as needed.
(5) Inspect the perirectal mucosa frequently for any signs of irritation or skin breakdown.
g) Patient and family education
(1) Teach patients and significant others to
(a) Maintain meticulous perineal hygiene, especially in the
presence of neutropenia.
(b) Apply appropriate barrier creams and medicated creams.
(c) Monitor carefully for any signs of infection or worsening
of tissue integrity.
(2) Ensure that patients and significant others are able to
(a) Identify the risk factors for perirectal cellulitis.
(b) Implement measures that minimize the risk of developing
perirectal cellulitis.
(c) Identify situations that require prompt professional intervention.
i. Pain, redness, or swelling in the affected area
ii. Body temperature > 100.4F (38C)
C. Cutaneous toxicity: Chemotherapy and its cutaneous side effects are an increasingly common source of injury to the skin, hair, and nails. For years,
the cutaneous side effects from conventional cytotoxic chemotherapeutic
agents have been observed and described in detail. More recently, the emergence of targeted chemotherapy drugs has widened the spectrum of adverse
cutaneous side effects seen in patients with cancer (Choi, 2011). See Table
31 for cutaneous reactions and management of toxicities from chemotherapy, biotherapy, and targeted agents.
1. Over the past decade, cancer therapy has increasingly shifted toward targeting specific pathways involved in the pathogenesis of malignancy. The
EGFR inhibitors (EGFRIs) are one of the best known examples of targeted therapy that are used both as first-line and adjuvant chemotherapy for solid organ cancers. These agents are less likely than traditional
cytotoxic chemotherapeutics to cause myelosuppression, infection, nausea, vomiting, and diarrhea. However, dermatologic adverse events from
EGFRIs, small molecule inhibitors, and mAbs such as gefitinib, erlotinib,
cetuximab, lapatinib, and panitumumab are significantly more common
than with cytotoxic agents, are symptomatic, and manifest in cosmetically sensitive areas (Wu, Balagula, Lacouture, & Anadkat, 2011). As the
number of agents and uses for targeted therapies increase, so does the
need to recognize and treat the dermatologic side effects of these agents.
2. Pathophysiology
a) EGFR is normally expressed in the epidermis, sebaceous glands, and
hair follicular epithelium, where it plays a number of important roles
in the maintenance of normal skin health, including control of differentiation, protection against damage induced by ultraviolet radiation, inhibition of inflammation, and acceleration of wound healing (Melosky et al., 2009).
b) Although not fully understood, inhibition of EGFR is believed to
cause follicular occlusion and rupture because of premature epithelial differentiation and an increase in the expression of genes that
Copyright 2014 by the Oncology Nursing Society. All rights reserved.

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Table 31. Cutaneous Reactions to Antineoplastic Agents


General Comments

Copyright 2014 by the Oncology Nursing Society. All rights reserved.

Chemotherapy

Biotherapy and Targeted Therapy

A number of chemotherapy drugs can cause hair changes and


Hair changes:
hair loss. Dose, route of administration, combination of drugs,
Alopecia, hirand other individual characteristics will influence occurrence as
sutism, hypertriwell as degree of hair loss.
chosis
Hair changes may occur 23 months after initiation of EGFRI
therapy, with hair thinning and developing a dry, brittle, or curly
texture (Segaert & Van Cutsem, 2005).
Hirsutism is characterized by excess hair growth in women in anatomic sites where growth is typically a male characteristic (beard,
mustache, chest, and abdomen) (Lacouture et al., 2010).
Hypertrichosis is characterized by hair density or length beyond
the accepted limits of normal in a particular body region or a
particular age or race (Lacouture et al., 2010).

Hair changes: Bexarotene, carboplatin,


cisplatin, cyclophosphamide, dactinomycin, doxorubicin, etoposide, hexamethylmelamine, ifosfamide, paclitaxel, vincristine
Alopecia: Carboplatin, cisplatin, cyclophosphamide, Ara-C, dacarbazine,
dactinomycin, daunorubicin, doxorubicin, etoposide, 5-FU, hydro