Prednisone

Vincristine

Daunorubicin

Doxorubicin

Idarubicin Asparaginase

ALL, hodgkins Lympholytic and incude apoptosis in lymphocytes. Quick but shorlived remission in acute leukemias. ALL, hodkins Binds B-tubulin blocks polymerization into microtubules, blocks cells in mitosis ALL, AML Anthracycline antibiotics tetracycline attached to duanosamine sugar. Generates free radicals Forms complex with topoisomerase II and DNA apoptosis Anthracyclin Antibiotic DNA intercalation Inhibits Topoisomerase II Free Radicals and H202 Needs NADPH, Cp450 and iron AML Just Like doxorubicin Used for ALL Deprives leukemic cell of Asn (inhibition of protein synthesis) Converts Asn to Asp and ammonia ALL, CLL Alkylating Agent Crosslinks N7 of guanine Need P53 Activated to phoshphamide mustard

Glucose intolerance, Immunosuppression, osteoporosis, psychosis

Neurological, constipation, myelosuppresion, alopecia Irreversible Cardiomyopathy Cardiotoxicity Red urine

Increase levels of Pglycoprotein(efflux pump) Efflux pump glutathione peroxidase activity or mutation in topo II. ability to repair DNA

Cardiac toxicity

S.O.D. and antioxidant efflux topo II

Hper glycemia,Nausea, Fever, Hepatotoxicity, increase risk of bleeding and clotting, depression, renal tox., pancreatitis, Increases neuro toxicity of vincristine Bladder (hemmorhagic cystitis)

Induction of Asp synthetase in tumor cells

Cyclophosphamide

Cytarabine

ALL, AML: Cytidine analogs Analog of 2 deoxycytidine 2 hydroxyl hinders rotation of pyrimidine base around nucleosidic

Myelosuppressive agent Cerebellar toxicity (dementia, seizures, coma

glutathione (Carbonium ion will attack over guanine) aldehyde DH DNA repair permeability p53 mutations has to be activated by p450 enzyme to work Anabolic and catabolic enzymes cytidine deaminase deoxydytidine kinase

6 -mercaptopurine

Mitoxanthrone

bond interferes with base stacking = apoptosis ALL Purine Analog HGPRT activates to TIMP - stops de novo purine synthesis Thio-GMP incorporated into DNA and RNA Inhibits PRPP aminotransferase AML with cardiac problems, CLL Intercalates with DNA Binds to topoisomerase II to cause strand breaks Lacks 4th ring not reduced in presence of iron no oxygen radicals Not as good as the others because lacks third MOA CML Inhibits ribonucleoside diphosphate reductase blocks ribo deoxyribonucleotides CML Forms DNA crosslinks inhibition of DNA synthesis and function Used with IFN- G Suppresses granulocyte counts CML; used in combo with hydroxyurea Inhibitory activity against ABL-BCR kinase Binds to ATP site to inhibit TK CLL Purine Analog Chain terminator when incorporated into DNA and RNAactivate apoptosis Inhibits : DNA - pol, primase, ligase and ribonucleside reductase

Myelosuppr ession Bone marrow toxicity Jaundice

HGPR T 6-MP thiouric acid alkaline phosphatase drug transport

No cardiac toxicity No free radicals Good for patients with heart problems

Hydroxyurea

Busulfan

Administered orally Gastric distress Mild myelosuppression Teratogen Leg ulcers Nausea and vomiting Myelosuppressive, thrombocytopenia, pancytopenia, impotence, sterility, fetal malformation, pulmonary fibrosis Edema, cramps Neutropenia Thrombocytopenia Nauea vomiting

Mutations in ribonucleoside diphosphate reductase

Imatinib mesylate (Gleevec)

Mutations in TK domains Amplification of BCRABL Drug efflux

Fludarabine

Myelosuppression, Nausea, vomiting, chills, fever, anorexia

deoxycytidine kinase (phosphorylates the drug) resistant to deamination because of fluorine group

Cladribine

Chlorambucil

HCL Chlorinated version of Fludarabine DNA strand breaks Apoptosis Inhibits ribo reductase Chain terminator Drug of choice for CLL Like cyclophosphamide: interferes with DNA replication and RNA transcription by alkylating and crosslinking Must be metabolized to add OH groups active Naked monoclonal Ab CLL and B-cell nonhodgkin lymphoma Targets CD 20 B-cell antigen Sensitizes lymphoma cells to apoptotic effects of alkylators. Synergistic with cyclophoshamide CLL: Targets CD52 on neuts and lymphs. Induces tumor cel death through Ab dependent cellular toxicity and complement activation Antibody against EGFR protein Used with irenotecan to colorectal cancer AML Conjugated monoclonal Ab Ab targeted against CD 33 antigen present on leukemic myeloblasts conjugated to calicheamicin cytotoxic antibiotic. Used for AML for relapsed patients; degrades the PML/RAR- protein. Induces apoptosis Hodgkins disease Nitrogen mustard

Resistant to deamination because of chlorine on ring deoxycitidine kinase (activating enzyme

Hypoplasia of Bone Marrow Myelosuppression (esp. less on megakaryocytes) Amenorrhea Pulm Fibrosis Less side effects compared with most alkylators Infusion rxn (swelling, bronchial collapse) Late onset of neutropenia and severe skin toxicity

Rituximab

*always given with cyclophoshamide or other alkylator kill by ADCC and CDC

Alemtuzumab

Infusion rxns, pancytopenia, opportunistic infections, depletion of hematopoietic cells Infusion rxn Skin rash Infusion rxn BM suppression Hepatic toxicity May lead to fatal veno occlusive disease Ab is used as a delivery vehicle. Calicheamicin is very toxic.

Cetuximab

Gemtuxumab Ozogamicin

Arsenic Trioxide

Mechlorethamine

Headache, lightheadedness, cardiac disrhythmias, fatigue, weight gain, fluid retention, dyspnea Nausea, vomiting Lacrimation

Alkylating agent

Procarbazine

Carmustine

Hodgkins disease and brain tumors Inhibit DNA, RNA, and protein synthesis Antineoplastic activity from conversion to highly reactive alkylating species which methylate DNA cyp mediated hepatic oxidative metabolism. Can cause chromosomal damage. Treats malignant glioma (Brain Cancer) only use Alkylates DNA (guanine) Carbomoylate proteins (attacks lysine) Intra and inter strand crosslinks of DNA

Myelosuppression Blocks reproductive fxn Very strong myelosuppression Always follow with peripheral stem cell rescue Leuko and thrombo cytopenia GI symptoms Carcinogenic acute leukemia Mutagenic Teratogenic Behavioral disturbances

ability to repair methylation of guanine by Guan-O6-alkyl transferase

Melphalan

Pentostatin

All trans Retinoic Acid

Multiple myeloma Direct Alkylator Similar to mechlorethamine Hairy Cell Leukemia Inhibitor of adenosine deaminase leads to buildup of adenosine and deosyadenosine nucleotides. These buildup and blocks DNA synthesis by inhibiting ribonucleotide reductase. Given in combo with cladribine Buildup of S-adenhomocysteine is toxic to lymphocytes Strand breakage Induces apoptosis in monocytoid leukema cells Acute promyelocytic

Effects DNA repair enzymes Carbamoylated protein = delayed or prolonged platelet suppression Very Severe myelosuppression Carcinogenic and mutagenic Crosses blood brain barrier (lipophilic) Hematological Nausea vomiting Alopecia at high doses Long lasting myelosuppression Fatal pulmonary toxicity with fludarabine GI symptoms Rashes Abnormal liver fxn

Fever, dyspnea,

Further mutation of

(tretinoin)

Leukemia Induces differentiation in tumor cells Displaces repressor and promotes degradation of the APL-RAR fusion gene

weightloss Cheilitis Bone tenderness Hyper lipidemia RA syndrome Hepatic enzyme abnormalities

fusion gene abolishing ATRA binding or loss of expression of fusion gene