Principles of Chemotherapy - Experimental Oncology Graduate Study

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Mechlorethamine (nitrogen mustard)Louis Goodman and AlfredGilman in San Francisco, 1955.• The first drug used for modern cancer CT, it is now used mainly to treatHodgkin's lymphoma as part of the MOPP regimen (combinedMechlorethamine-vincristine (Oncovin)-Procarbazine-Prednisone).• Problems with clinical use because of its high reactivity.• Because of its rapid reaction rate, mechlorethamine must be given i.v.• As with all alkylating agents, bone marrow function is depressed.12
Melphalan (LMelphalan(L-phenylalanine mustard)• One of several modified mustards thatwere synthesized in an attempt toproduce a drug that would preferentiallylocalize in a particular tumor.• Phenylalanine is a precursor of melanin; a phenylalanine mustard derivativemight accumulate in melanomas and produce a selective toxicity.• Although this effect was not achieved, melphalan is a very useful drug.• The presence of the electron-withdrawing aromatic ring next to the nitrogenslows the rate of cyclization (immonium ion formation) and thus of alkylation,making melphalan much less reactive than mechlorethamine.• This allows time for absorption and wide distribution before extensivealkylation occurs.• It also means that the drug can be given orally.• Melphalan crosslinks DNA in a manner similar to mechlorethamine.• Principally used to treat multiple myeloma; also ovarian/breast tumors.• Major toxicity is bone marrow suppression.13
Page 1 and 2: ONCOLOGY 520CHEMOTHERAPYLecturer: D
Page 3 and 4: Combination CT• Improvements in C
Page 5 and 6: Therapeutic Index, contd.• Such d
Page 7 and 8: Relationship between remission and
Page 9 and 10: Classes of anticancer drugs• “C
Page 11: a. Nitrogen mustards• Bifunctiona
Page 15 and 16: . Chloroethyl nitrosoureas• The 2
Page 17 and 18: 2. AntimetabolitesDrugs that resemb
Page 19 and 20: Antimetabolites, contd.Cytosine ara
Page 21 and 22: Natural products, contd.Actinomycin
Page 23 and 24: Natural products, contd.VP-16 and V
Page 25 and 26: 4. “Platinating” agents: Cispla
Page 27 and 28: 1. Transport• Mutation/altered ex
Page 29 and 30: Nucleoside analog responsiveness an
Page 31 and 32: 2. Glutathione and associated enzym
Page 33 and 34: 4. Tolerance to DNA damage• In ma
Page 35 and 36: 5. Drug-specific mechanisms• Ctx:
Page 37 and 38: Cell-cycle phase specificity of CT
Page 39 and 40: [2] Use of high-dose CT through ove
Page 41 and 42: Bone marrow transplantation and gen
Page 43 and 44: Gleevec (imatinib mesylate), former
Page 45 and 46: Hypoxic-cell cell cytotoxins: Tirap

Principles of Chemotherapy - Experimental Oncology Graduate Study

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