ManagementofSideEffectsfromChemotherapy

Dr.CarolKwok
ClinicalOncologist,DepartmentofOncology,PrincessMargaretHospital

Introduction
Chemotherapyisanimportantmodalityincancertreatment.Chemotherapydrugsactby
damaginghighproliferatingcells.Byvirtueofdifferencesinbothbiologicalandproliferation
characteristics,chemotherapycausesagreaterproportionofcelldeathamongneoplasticas
opposedtonormalcells.Damagetonormalcellsresultinchemotherapytoxicitiesandside
effects,itcanbeseenthatthoseactivelydividingtissuessuchbonemarrow,hairfolliclesand
gastrointestinalmucosaaremostvulnerable.

Side effects of chemotherapy range from mild,

likenonspecifictirednesstolifethreateningasin
neutropenic fever. They can be classified into
haematological, gastrointestinal, dermatological,
renal, pulmonary, cardiac, neurological, hepatic
and gonadal toxicities. It is important that
doctors and nurses are knowledgeable regarding
the drugs adverse effects and expected time of
occurrence, and know how to prevent, minimize
and manage them. Patients and families
education is also important, as many side effects
will occur when the patient is at home. In
managing side effects, assessment for patients

tolerancetothepriordoseandearlyintervention
playapivotalroleinapatientsoutcome.Tominimizeorpreventtoxicity,chemotherapywill
onlybeadministeredifthereisadequatebaselinebloodpicture,renalandliverfunctions,no
contraindicationwithregardtounderlyingmedicalconditions,andforcertainchemotherapeutic
agents,furtherchemotherapyisdiscontinuedifcumulativedoseshavereachedtolerancelevels.
Inthisbooklet,medicalaspectsinpreventionandmanagementofchemotherapysideeffects
willbediscussedalongwithsomenonpharmacologicalmeasures.

Haematological
Whitebloodcells(specificallyneutrophils),redbloodcellsandplateletarethethreemain
componentsofbonemarrow;theyareresponsibleforprotectingthebodyfrominfection,
transportingoxygeninthecirculationandbloodclottingmechanismrespectively.
Management of side effects from chemotherapy_________________________________________________________

___________ 1/7

Chemotherapycausesbonemarrowsuppressionresultinginneutropenia,anaemiaand
thrombocytopenia.

Neutropenia
Neutropeniaisdefinedasanabsoluteneutrophilcount(ANC)
lessthancells/mm 3 .Neutrophilcountsusuallydroptoitslowest
levelonday714postchemotherapyformajorityofthe
chemotherapyregimens,whichiscommonlyreferredasnadir.
Thereisaninverserelationshipbetweenthedegreeand
durationofneutropeniaandriskofinfection.Patientswithan
ANC<100cells/mm3orthosewithprolongedneutropenia(>7
days)areatsignificantlyhigherriskforseriousinfection.

Forafebrileneutropenicpatients,thegoalistopreventinfectiouscomplicationordetect
infectionattheearliestpossiblestageandpromptlyintervene.Patientandfamilyeducation
shouldinclude:

Explanationofthefunctionofwhilebloodcells
Meaningofnadir
Instructionsfortemperaturetaking
Signsandsymptomsofinfection(e.g.fever,malaise,thoserelatedtospecificorganssuch
ascough,urinaryfrequencywithorwithoutdysuria,etc.)
Hygienepracticesemphasizinghandwashing
Identificationandassessmentofhighriskareasforinfection(chest,urinarytract,skin)
Careofaccessdevices(e.g.Hartmanline,urinarycatheter)
Avoidanceofexposuretopersonswithcommunicableorinfectiousillnesses,stayaway
fromcrowdsandanimals
Maintainnutritionalstatusbyabalanceddiet
Specificdirectionsforaccesstohealthcaresystems(clinicorA&Eifemergency)

Febrileneutropenia(FN)
Feverisdefinedasasingleoraltemperatureof38.3 o C
(101 o F)oratemperatureof38.0 o C(100.4 o F)for1hr.
Thedevelopmentoffeverinaneutropenicpatient
representsanurgentclinicalproblemrequiringprompt
assessmentandintervention.Morethanhalfofpatients
willnotexhibitanyothersignsorsymptomsofinfection.
Besidesempiricantibiotictherapy,suggestedguidelines
forcareofthehospitalizedneutropenicpatientinclude
thefollowing:

z Washhandsfrequentlyandthoroughly;thisisthesinglemostimportantmeasurein
preventinginfection.Useclean,disposablegloveswitheachpatient
z Placepatientinaprivateroom
Management of side effects from chemotherapy_________________________________________________________

___________ 2/7

z
z

Avoidpersonswithviralorcontagiousillnesses
Cleananddisinfectequipmentbeforepatientcontactandaftereachuse

Anaemia
Anaemiapresentswithsymptomsofdyspnoea,dizziness,headacheandpalpitation.Apartfrom
directeffectsofcytotoxicdrugs,otherfactorsthatcontributetoanaemiainacancerpatient
includediminishednutritionalstores,anaemiaofchronicdisease,bloodloss,cumulativemarrow
suppressionassociatedwithpriortreatment,decreasederythropoietinproduction,etc.A
thoroughlaboratoryassessmentisrecommendedtoidentifythecauseoftheanaemia.Red
bloodcelltransfusionorhumanrecombinanterythropoietinarethetreatmentoptions.
Generally,bloodtransfusionisindicatedforanacuteneed,suchasbloodlossorsymptom
severitythatwarrantspromptintervention.Foranaverageadult,oneunitRBCtransfusion
raisesthehaemoglobinby1g/dl.Humanrecombinanterythropoietinhasbeenshownto
decreasetheneedfortransfusionsupport,andimprovesqualityoflifeforpatientson
chemotherapy.Sincenotallpatientswillbenefit,patientsshouldbemonitoredandassessedat
regularintervalsforresponseanddecisionstocontinueordiscontinue.

Thrombocytopenia
Thrombocytopenia(plateletcountoflessthan
100,000/mm 3 ,or100x10 9 /L)isapotentialoractual
doselimitingsideeffectforanumberof
chemotherapyagents.Somecytotoxicagentse.g.
carmustine,lomustine,exhibitdelayedonset
thrombocytopeniaandhaveacumulativedoseeffect.
Increasedriskofbleedingisthemostsignificant
outcomeofareducedplateletcount.Amoderaterisk
ofbleedingexitswhentheplateletcountfallstoless
than50,000cells/mm3 ,andmajorriskisassociated
withplateletcountslessthan10,000cells/mm 3 .

Clinicalmanifestationsincludeeasybruising,petechiae,purpura,gumbleedingand
hypermenorrhoea.Topreventorminimizebleedinginpatientswithamoderatetosevererisk,
thefollowingguidelinesforpracticearerecommended:
Avoidintramuscularinjections
Avoidtrauma
Decreasethepatientslevelofactivity
Avoiddrugsthatalterplateletfunctionorclotting(e.g.aspirinandnonsteroidalanti
inflammatorydrugsandanticoagulants;certainherbs)
PressureshouldbeappliedforatleastfiveminuteswithapressurebandageforallIV
injections,venipunctures,andbonemarrowprocedures
Patientsshouldavoidblowingtheirnosesandsneezing.Forshaving,anelectricrazoris
recommended

Management of side effects from chemotherapy_________________________________________________________

___________ 3/7


Gastrointestinal
Gastrointestinal side effects include nausea and vomiting, anorexia and taste changes, oral
mucositis,diarrhoeaandconstipation.

Nauseaandvomiting

Nauseaandvomitinghavebeenrankedthefirstand
secondworstsideeffectsofchemotherapyfromthe
patientspointofview.Indeed,somepatientsfear
vomitingsomuchthattheyarereluctanttoundergo
chemotherapy.Therefore,controlofemesismustbea
priorityforallpatientsundergoingchemotherapy.
Female,especiallywithhistoryofemesisinpregnancy,
youngage,nondrinkerandpooremeticcontrolduring
priortreatmentareriskfactorsforchemotherapyinduced
nauseaandvomiting.

Therearethreepatternsofnauseaandvomitingassociatedwithchemotherapy:acute,delayed,
andanticipatory.Acutenauseaandvomitingoccurswithinthefirst24hoursoftherapy(usually
within1to2hours)andisgenerallymostsevereduringtheinitial4to6hours.Theincidenceand
severityofnauseaandvomitingarerelatedtotheemetogenicpotentialofthedrug(Table1).
Knowledgeofemetogenicpotentialofdrugsisthebasisforchoosingtheappropriate
antiemeticsforpatients.Delayedemesishasbeenarbitrarilydefinedasoccurring24ormore
hoursafterchemotherapyandmaylastfromonetosevendays.Itismostcommonlyassociated
withcisplatin,carboplatin,cyclophosphamide,anddoxorubicin.Delayedorresidualnauseaand
vomitingoccursevenwhenantiemeticsareeffectiveinpreventingacutesymptomswithinthe
first24hours.Anticipatoryemesisistheexperiencingofnauseaand/orvomitingbefore
receivinganotherchemotherapytreatment.Itisaconditionedorlearnedresponsetoprevious
effectsfromtherapyandassociatedenvironmentalstimuli,inmostinstances,itwasassociated
withapriorexperiencewhentherewasinadequatecontrolofemesis.Therefore,patientsmust
begivenoptimalantiemeticregimenwiththeirinitialcourseofchemotherapytopreventacute
anddelayedemesis,and,consequently,anticipatoryemesis.Breakthroughemesisrefersto
nauseaorvomitingdespiteoptimalprophylacticpretreatmentand/ordelayedtherapy.

Generalprinciplesforsuccessfulantiemetictherapyforchemotherapyinducednauseaand
vomitinginclude:

Aggressivetherapyforchemotherapynavepatients
Adequatedurationofcoveragewithantiemeticsforthepredictedriskperiodof
symptoms
Appropriateselectionofagentsanddosingaccordingtotheemeticpotentialofthe
chemotherapy

Management of side effects from chemotherapy_________________________________________________________

___________ 4/7

Oralmucositis
Theonsetoforalmucositisorstomatitistypicallyoccurs5to7daysafterchemotherapy,and
healingoccurs10to14daysaftercessationoftherapy.Indirecteffectsontheoralmucosa
occur12to14daysafterchemotherapy,duringthegranulocytenadir.Patientsmaybeatrisk
forlocalinfection.Mucositiscausesmildtoseverediscomfort,affectsfluidandnutritional
intake,andinterfereswithspeech.
Thegoalofcareforpatientatriskorwith
mucositisistomaintaintheintegrityofthe
oralmucosa,preventsecondaryinfection,
providepainreliefandmaintaindietary
intake.Dietaryguidelinesformaintain
nutritionalstatusforpatientswithoral
mucositisare:
z Avoidfoodsthatareirritatingtooral
mucosa,especiallyspiced,acidic,or
saltedfoods
z Useblenderizedfoodsifnecessary.
Avoidextremelyhotorcoldfoods
z Takeextracalorieswithpowdered

milkordietarysupplements
Patientsshouldmaintainahighproteindiet

Encouragefluids.Fruitjuicesmaybesoothingtooralmucosaandaddextracalories

Diarrhoea
TheGItractissusceptibletochemotherapytoxicitybecauseoftherapidturnoverofthe
mucosalcells.Theagentsmostcommonlyassociatedwithdiarrhoeaarecapecitabine,5
fluorouracil(especiallyinhighdoseorincombinationwithleucovorinoroxaliplatin),irinotecan,
methotrexateandtopotecan.Irinotecanisspecificallyassociatedwithearly(within24hours)
andlateonset(3to11daysposttherapy)diarrhoea.Earlyonsetdiarrhoea,oftenprecededby
diaphoresisand/orabdominalcramping,canbeamelioratedbytheadministrationofatropine.

Anorexiaandtastechanges
Cytotoxicdrugtherapycancauseanorexia.Patientmayexperiencemetallictasteafterdrug
therapy,agenerallossoftasteforfood.Forpatientswhoexperiencealossofsenseoftaste,a
varietyofsimpleinterventionscanbehelpfulsuchassuckingonsourcandies,usingaromato
improveappealoffood,useofplasticutensilsiffoodtastesmetallic,andchewingsugarfree
gum.Dietitianadviceandnutritionalsupportaregiventopatientswithanorexia.The
importanceofeatingdespiteanorexiashouldbeemphasized,withfoodintakeidentifiedasa
componentofthetreatmentplan.

Management of side effects from chemotherapy_________________________________________________________

___________ 5/7

Dermatological
Dermatologicaltoxicitycanbelocalandsystemic.Local
toxicityoccursinthetissuessurroundingthesiteofdrug
administrationandisdescribedbyavarietyofvenousand
cutaneousresponses:phlebitis,urticaria,pain,erythema,
veindiscoloration,andtissuenecrosissecondaryto
extravasationofadrug.Hairlossisthemostcommon
systemicmanifestation.Othersystemicdermatological
effectsincludedermatitis,nailchanges,hyperpigmentation,
urticaria,photosensitivityreactions,handfootsyndrome,
andradiationrecallreactions.

Alopecia
Theactualexperienceofcompleteornearlycompletehairloss
hasoftenbeendescribedbypatientsasthemostdevastating
sideeffectofchemotherapy.Hairisanintegralpartofphysical
appearance,anditslossmaynegativelyaffectselfimage,body
image,copingskills,andsocialinteractions.Thedegreeof
distressmaybeminimizedbyadequatepreparationfortheloss,
possibleinterventions,andongoingsupportfromhealthcare
professionalsandfamilymembers.

Hairlossfromchemotherapyisreversible.Manytimeshair
beginstoregrowdespitecontinuedtherapy,anditisnot
unusualfornewhairtoreappeartwotothreemonthslater.
Nursesanddoctorsshouldmakeeveryefforttoprovide
accurateinformationandsupporttopatientsatriskforhair

loss.Patientsareshockedwhentheyexperiencehairlossunexpectedly,andthepurchaseofa
wigorheadcoveringbeforelossofmorethan50%ofhairoccurs,maydecreasethedistress.
Interventionstohelpmaximizepatientadjustmentandminimizethedistressassociatedwith
hairlossincludethefollowing:
z Explaintopatienttherationalefortheoccurrenceofalopecia,therelativeincidence,and
thedegreeofhairlossexpectedspecifictothechemotherapydrug(s)prescribed
z Encouragethepatienttoexpressemotionsregardingtheinformationprovided
z Reiteratethefactthathairregrowsandthatchangesincolourandtexturemayoccur(e.g.
curlyorgray)
z Discouragetheuseofdryers,hotrollers,andcurlingirons,sincetheymayfacilitate
increasedhairloss
z Protecttheheadfromthesunwithahatorsunscreenforcompleteornearlycomplete
alopecia
z Maintainscalpcleanlinessandconditioningaftertotalalopecia
z Suggesttocutthehairshortbeforechemotherapy,oruseofwigs,capsorscarvesifwish

Management of side effects from chemotherapy_________________________________________________________

___________ 6/7

Extravasationanditsmanagement
Potentiallocaltoxiceffectsfromchemotherapeutic
drugsrangefromtransientlocaldiscomfortduring
administrationtoseveretissuenecrosiswithpotential
damagetotendonsandnerves.Chemotherapeutic
drugshavebeendescribedasirritantandvesicant.An
irritantisadrugthatcauseslocalvenousresponse,
patientmaycomplaintendernessalongtheveinand
maybeaccompaniedbyerythema,whichareusually
shortlivedandsubsequenttissuedamageisuncommon,andnecrosisdoesnotoccur.

Gonadal
Chemotherapycausesgonadaldysfunction,resultinginsterilizationordecreasedfertility.In
men,cytotoxicdrugsinducereductioninspermcountsduringchemotherapy,whichcanbe
temporaryorprolonged,dependingonthenatureofthecytotoxicagentanddose.Inwomen,
chemotherapycancausedestructionofoocytes,whichcanleadtoovarianfailureand
prematuremenopause.Thechanceofhavingearlymenopauseincreasesastheageincreases.

Beforeinitiatingchemotherapy,patientsshouldbeinformedofthepotentialriskofsterility
fromtheplannedcytotoxictherapyandsemencryopreservationisofferedtoallmalepatients
interestedinhavingchildrenafterthecompletionofcytotoxictherapy.

Duringtreatment,sexualrelations
betweenpartnersmaycontinue,but
reliablecontraceptivemethodsshouldbe
used.Ifconceptiondoesoccurduringthe
courseoftreatment,thecoupleshould
beinformedoftheriskandevaluatethe
continuationofpregnancy.Itis
recommendedthatpatientswait6
monthsaftertheendoftherapybefore
attemptingtoconceive.Iffertilityispreserved,thepatientsshouldbeinformedofthehigh
probabilityofhavinghealthychildren.Althoughtherearetheoreticalconcernsaboutcongenital
malformationsandgeneticdiseaseinoffspring,thelimiteddataforhumansindicateno
measurableexcessriskabovethebackgroundlevelof4%,butsmall(lessthantwofold)increases
couldhaveescapeddetection.Anypregnancyaftertherapyshouldbemonitored(with
ultrasoundandpossiblyamniocentesis)becauseofthepotentiallyincreasedgeneticrisk.
Womenshouldalsobetoldabouttherisksofchemotherapyinducedprematuremenopause.If
thisdoesoccur,itisimportanttopresentabalanceddiscussionofpotentialbenefitsofprompt
initiationofhormonereplacement(increasedbonemineraldensityandreducedincidenceof
fracture)aswellasrisk(cardiovasculardiseaseandbreastcancer)sothatanindividually
appropriatedecisionmaybereached.Ifawomanhasanintactuterus,estrogenshouldbe
combinedwithprogesteronetopreventendometrialhyperplasiaandcancer.

Management of side effects from chemotherapy_________________________________________________________

___________ 7/7