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Chemotherapy Drugs

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Drug Class Drug Name(s) Cell Cycle Mecanism of Action Specific Indications Important Side Resistance

Specificity (if any) Effects Mechanisms

Antimetabolites (folate Methotrexate, S Phase Inhibits DHFR (blocks Multiple Myelosuppression Drug efflux pump

antagonists) Pemetrexed DNA synthesis by malignancies (give Leucovorin to (MDR)

inhibiting THF (choriocarcinoma, alleviate severe BM

production). ALL, breast cancer, suppression),

Pemetrexed also lung cancer, NHL), hepatotoxicity, renal

inhibits thymydilate autoimmune toxicity.

synthase. disorders, abortion *IT Admin: Causes

arachnoiditis and

chronic demyelinating

encephalopathy.

Pyrimidine antagonist 5-FU, Capecitabine S Phase Inhibits thymydilate Liver, head/neck, Myleosuppression. In

synthase to prevent Ovarian, Cervical those with

nucleotide synthesis cancers dihydropyrimidine

and therefore DNA dehydrogenase

synthesis deficiency, life

threatening toxicity

can occur

Pyrimidine Antagonist Cytarabine (Ara-C) S Phase Competitively inhibits AML, ALL, CML, CNS Myelosuppression,

DNA polymerase and leukemia, NHL cerebellar dysfunction

terminates DNA (with high doses)

elongation by

incorporation

Pyrimidine Antagonist Gemcitabine S Phase Incorporates into the Bladder, breast, Myelosuppression

DNA strand and ovarian,

prevents elongation mesothelioma,

and repair NSCLC

Pyrimidine Antagonist Azacitidine, S Phase Hypomethylation of MDS Myelosuppression,

Decitabine DNA with some direct cardiac complications

toxicity on abnormal (decitabine)

cells

Purine Antagonist Fludarabine, S Phase Adenosine analogs CLL, NHL, AML, Hairy Myelosuppression

Cladribine, that inhibit DNA Cell Leukemia w/OI, tumor lysis

Pentostatin synthesis and repair syndrome, peripheral

& RNA function neuropathy

(fludarabine),

Purine Antagonist 6-mercaptopurine, 6- S Phase Converted to active ALL, CML, AML, NHL Myelosuppression. HGPRT Deficiency

TG form by HGPRT When given with

(purine salvage allopurinol can cause

enzyme) Inhibits de- overdose. VOD

novo purine (severe liver failure)

synthesis.

Antimetabolites Hydroxyurea S Phase Inhibits AML, sickle cell Myelosuppression

ribonucleotide anemia

reductase leading to

decreased DNA

synthesis

Antimicrotubules/ Vincristine, Metaphase Binds to tubulin and Multiple Peripheral Efflux Pump

vinca alkaloids. Vinblastine, inhibits microtubule hematologic neuropathy, (MDR), alterations

(Metabolized by Vinorelbine assembly which leads malignancies and myelosuppression, if in  and β tubulin

CYP450) to cell arrest some solid tumors given IT causes severe

fatal ascending

paralysis.

Taxanes Paclitaxel, docetaxel, Metaphase Enhances tubulin Multiple solid Hypersensitivity Efflux Pump

(Metabolized by abraxane (albumin cross linking which tumors Reactions (decreased (MDR)

CYP450) bound paclitaxel) blocks normal cell with use of abraxane),

reproduction fluid retention,

peripheral

neuropathy

Epothilones-LOW Ixabepilone G2-M Binds B tubulin to Multidrug resistant Peripheral LOW

SUSCEPTIBILITY TO Arrest promote proliferation metastatic breast neuropathy, alopecia SUSCEPTIBILITY

RESISTANCE and prevent cancer TO MDR

breakdown of mitotic

spindles

Asparaginase G1 Hydrolyzes L- ALL Hypersensitivity

asparagine causing reactions, decreased

dysfunctional protein clotting factors

synthesis

Topoisomerase Irinotecan, G2 Stabilizes a cleavable Ovarian cancer Myelosuppression, Topoisomerase

Inhibitor topotecan topoisomerase1-DNA (topotecan), dose limiting diarrhea. alterations, MDR.

(camptothecin complex (ATP colorectal cancer

analogs) independent) leading (irinotecan)

to SS DNA strand

breakage upon

replication

Topoisomerase Etoposide G2 Inhibits Multiple Dose limiting

Inhibitor topoisomerase II (ATP malignancies myelosuppression,

(Epipodophyllotoxins- dependent) leading to secondary AML

plant alkaloid) DS DNA strand

breakage

Topoisomerase Mitoxantroene G2 Inhibits Refractory prostate Bluish sclera, urine,

Inhibitor topoisomerase II cancer, AML and fingernails

causing cross linking

and DS DNA breaks

Anthracyclines Doxorubicin, Doxil G2 Inhibits Dano: ALL, AML Arrhythmias, Efflux Pump

(topoisomerase (liposomal topoisomerase II, Doxo: Multiple cardiomyopathy, (MDR), point

inhibitor) doxorubicin) intercalates between hematologic and pericarditis, CHF. mutations on

Danorubicin, base pairs disrupting solid tumors Cardiac sideFx be topoisomerase II,

Epirubicin, Idarubicin DNA and RNA decreased by inactivation of

synthesis, produces administration of superoxide free

oxygen radicals, and dexrazoxane. radicals

disrupts ion and fluid

balance

Alkylating Agents Cisplatin, Nonspecific Alkylating agent that Multiple solid Peripheral Impaired influx or

(Platinums) Carboplatin, cross links and tumors (primarily neuropathies, enhanced efflux

Oxaliplatin alkylates DNA. Causes genitourinary and tinnitus, renal failure, pumps, cytosolic

fragmentation by gastric malignancies) SIADH, metallic taste drug inactivation,

repair enzymes and DNA repair,

prevention of DNA & altered apoptotic

RNA synthesis. processes

Alkylating Agents Cyclophosphamide, Nonspecific Alkylating agent that Breast, Ovarian, NHL, Hemorrhagic cystitis,

(Nitrogen Mustards) Ifosfamide, cross links and CLL, MM, myelosuppression

Melphalan, alkylates DNA. Causes Lymphomas

Chlorambucil fragmentation by

repair enzymes and

prevention of DNA &

RNA synthesis.

Alkylating Agents Carmustine Nonspecific Alkylating agent that Brain tumors Myelosuppression,

(nitrosureas) can cross the BBB pulmonary fibrosis

Alkylating Agents Busulfan Nonspecific Alkylating agent Bone marrow Myelosuppression,

transplant hepatotoxicity,

pulmonary fibrosis

Non-classical Temozolomide Nonspecific Methylates guanine GBM Leukopenia,

Alkylating Agent residues preventing thrombocytopenia

DNA and protein

synthesis

Antitumor Antibiotic Bleomycin G2 Causes production of Testicular cancers Pulmonary fibrosis

oxygen free radicals

that damage DNA

Arsenic Trioxide Arsenic Trioxide Nonspecific Causes apoptosis of APL Prolonged QT

cells syndrome

All-trans retinoic acid ATRA N/A Induces maturation of APL Vitamin A toxicity

(ATRA) blasts in APL

Hormonal Agents Tamoxifen N/A Competitive estrogen Estrogen receptor + Endometrial cancer,

receptor antagonist breast cancers, thromboembolism,

that blocks the effects osteoporosis hot flashes, vaginal

of estrogen in tumor bleeding

cells while

potentiating normal

estrogen function

elsewhere in the body

Hormonal Agents Fulvestrant N/A ER antagonist Metastatic ER+ Hot flashes,

breast cancer arthralgias, headache

Hormonal Agents Anastrozole, N/A Aromatase inhibitor ER+ breast cancer Hot flashes,

Letrozole, blocks the arthralgias, headache

Exemestane transformation of

testosterone into

estrogen

Hormonal Agents Leuprolide, Goserelin N/A GHRH Antagonists Breast and prostate Hot flashes,

cancers impotence, decreased

libido,

Hormonal Agents Bicalutimide, N/A Androgen receptor Prostate cancer Decreased libido,

Nilutamide, blocker gynecomastia,

Flutamide myalgias,

hepatotoxicity

Topoisomerases are enzymes that unwind and wind DNA, in order for DNA to control the synthesis of proteins, and to facilitate DNA replication

Topoisomerase I Topoisomerase II

 Acts on one strand of DNA  Acts on both strands of DNA

 Removes negative supercoils  Removes positive supercoils

 No involvement in DNA replication  Involved in DNA replication

 Expression is continuous during G2 phase of the cell cycle and in  Expression increases during S phase of the cell cycle & is almost absent in qu

quiescent cells cells

 ATP independent  ATP dependent



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