Cancer Chemotherapy: Drug Classification and Mechanism of Action

Cancer Chemotherapy: Drug Classification and Mechanism of Action
1. Polyfunctional alkylating agents Cyclophosphamide (Cytoxan) fosfamideMechlorethamineMelphalan (Alkeran)Chlorambucil (Leukeran) Secondary agentsThiopeta (Thioplex) Ovarian cancerBusulfan (Myleran) Chronic myeloid le...ukemiaOther Alkylating Drugs Procarbazine (Matulane)Dacarbazine (DTIC)Altretamine (Hexalen)Cisplatin cisplatin (Platinol)Pharmacological Effects: Polyfunctional Alkylating Drugs Injection site damage (vesicant effects) and systemic toxicity.Toxicity: dose relatedprimarily affecting rapidly dividing cells bone marrow GI tract nausea and vomiting within less than an hour-- with mechlorethamine, carmustine (BCNU) or cyclophosphamideEmetic effects: CNS reduced by pre-treatment with phenothiazines or cannabinoids.gonadsCyclophosphamide cytotoxicity depends on activation by microsomal enzyme system. Hepatic microsomal P450 mixed-function oxidase catalyzes conversion of cyclophosphamide to the active forms: 4-hydroxycyclophosphamidealdophosphamide Major Toxicity: bone marrow suppression dose-related suppression of myelopoiesis: primary effects on megakaryocytesplateletsgranulocytesBone marrow suppression is worse when alkylating agents are combined with other myelosuppressive drugs and/or radiation (dose reduction required)If bone marrow suppression is severe, treatment may have to be suspended and then re--initiated upon hematopoietic recovery.Long-term consequences of alkylating agent treatment include: ovarian failure (common)testicular failure (common)acute leukemia (rare)Oral Route of Administration:Cyclophosphamide (Cytoxan)Busulfan (Myleran) Other Alkylating DrugsProcarbazine (Matulane) Methylhydrazine derivativeActive in Hodgkin's disease (combination therapy)Teratogenic, mutagenic, leukemogenic. Side effects: nausea, vomiting, myelosuppressionhemolytic anemiapulmonary effectsDacarbazine (DTIC) Clinical use: MelanomaHodgkin's diseasesoft tissue sarcomaSynthetic drug; requires activation by liver microsomal system.Parenteral administration Side effects: nausea, vomiting, myelosuppressionAltretamine (Hexalen) Clinical use: alkylating agent-resistant: ovarian carcinomaActivated by biotransformation (demethylation) Side effects: nausea, vomiting, central and peripheral nervous system neuropathies.relatively mild myelosuppressive effects.Cisplatin (Platinol) Clinical use: Genitourinary cancers testicularovarianbladderIn combination with bleomycin and vinblastine: curative treatment for nonseminomatous testicular cancerCarboplatin (less GI and renal toxicity; with myelosuppressive toxicity): alternative to cisplatinInhibits DNA synthesis; cross-linking; guanine N7 sitePlatinum compounds: synergistic with other anticancer agentsSite effects: major acute effect: nausea, vomitingrelatively little bone marrow effectssignificant renal dysfunction (minimized by adequate hydration/diuretics)acoustic nerve dysfunction

-------------------------------------------------------------------------------------------------------------------- 2. AntimetabolitesMethotrexatePurine antagonists Mercaptopurine (6-MP)Thioguanine (6-TG)Fludarabine PhosphateCladribine (Leustatin)Pentostatin (Nipent)Pyrimidine antagonists Fluorouracil (5-FU)Cytarabine (ARA-C)AzacitidinePlant alkaloids Vinblastine (Velban)Vincristine (Oncovin)Etoposide (VP-16,VePe-sid)Teniposide (Vumon)Topotecan (Hycamtin)Irinotecan (Camptosar)Paclitaxel (Taxol)Docetaxel (Taxotere)

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3. Antibiotics Anthracyclines Doxorubicin (Adriamycin, Rubex, Doxil) Daunorubicin (DaunoXome) Dactinomycin (Cosmegen)Idarubincin (Idamycin)Plicamycin (Mithramycin)Mitomycin (Mutamycin)Bleomycin (Blenoxane)

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4.
Hormonal agents Tamoxifen (Nolvadex)Flutamide (Eulexin)Gonadotropin-Releasing Hormone Agonists (Leuprolide and Goserelin (Zoladex))Aromatase Inhibitors AminoglutethimideAnastrozole (Arimidex)-----------------------------------------------------------------------------------------------------------------Miscellaneous anticancer drugs AmsacrineHydroxyurea (Hydrea)Asparaginase (El-spar)Mitoxantrone (Novantrone)MitotaneRetinoic Acid DerivativesBone Marrow Growth FactorsAmifostine