1. C. The most likely reason for resistance to 5-fluorouracil or other agents that require activation is that tumors can no longer activate the drug. There is no evidence that 5-fluorouracil becomes unable to penetrate tumor cells. There may be an increase in P-glycoprotein, but this is not usually associated with 5-fluorouracil. There may be an induction in the drug metabolism for some antineoplastic drugs, but this does not appear to be the case for 5-fluorouracil. Increased metallothionein content has been associated with resistance in the case of cisplatin but not 5-fluorouracil.

2. C. The dose-limiting toxicity of bleomycin is pulmonary toxicity and that of cisplatin is renal. Doxorubicin produces cardiotoxicity; hematoxicity is dose limiting for methotrexate.

3. E. Dactinomycin is a class 3 agent, that is, an agent that kills proliferating cells in preference to resting cells. Hydroxyurea and cytarabine are class 2 agents that specifically kill cells in S-phase. Bleomycin is a class 2 agent that is specific for cells in G2 and early M-phase. Mechlorethamine (class 1) appears to kills normal and malignant cells to about the same extent.

4. A. Carmustine and mechlormethamine kill both normal and malignant cells to the same extent. Hydroxyurea and bleomycin kill cells preferentially in specific phases of the cell cycle. Hydroxyurea is specific for S-phase, while bleomycin is most toxic to cells in G2- and early M-phase. Flurouracil is cy-totoxic in G1 and G2 phases.

5. E. Intensive intermittent schedules allow time for recovery from the acute toxic effects of the antineo-plastic agents. If a drug has no activity by itself, it is not likely to be beneficial in a combination. It is important not to include two drugs with the same dose-limiting toxicity. Most curable tumors require at least six to eight cycles of therapy.

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