The Drugs

For a complete understanding of the use of individual and combination regimens, a brief description of the more commonly used drugs is presented. Cisplatin (P) and carboplatin are platinum-based compounds. These agents differ in that carboplatin has fewer side effects (especially renal failure and hematogenesis) and is slightly less efficacious. Their mechanism of action is by binding to DNA strands and causing multiple chain breaks in dividing cells, eventually leading to cell death. Major toxicities include acute renal failure, neuropathy, ototoxicity, severe emesis, and occasional myelosuppression.1'2

The antimetabolites include methotrexate (a folate antagonist), 5-fluorouracil (5-FU), and gemcitabine (pyrimidine analogues), and 6-mercaptopurine (a purine analogue). They exert their action by disrupting DNA chain elongation, either by directly incorporating into the chain or by depleting the cells of necessary enzymes. Toxicities include myelosuppression, thrombocytopenia, nausea and vomiting, and mucositis.1,2

The most commonly used antibiotics (anthracyclines) are doxorubicin (Adriamycin), bleomycin (B), and mitomycin C (Mito). These agents act by producing intracellular free radicals (requiring a well-oxygenated tumor), damaging the DNA chain in association with topoisomerase. Cardiac and pulmonary side effects predominate, particularly pulmonary fibrosis and arrhythmias and, with larger doses, congestive heart failure.1,2 Vincristine, vinblastine, and the newer agent, vinorelbine, are plant alkaloids that bind to tubulin, interrupting the mitotic spindle and preventing the cell from completing meiosis. Partially irreversible peripheral neuropathy, gastrointestinal cramping, and mild myelosuppression are side effects noted with these agents.1,2 The newest group is the taxoid family, consisting of pacli-taxel (Taxol) and docetaxol (Taxotere). In contrast with the vinca alkaloids, these drugs stabilize the microtubules, eventually causing the cells to accumulate arrays of disorganized microtubules, leading to cell death. As with the vinca alkaloids, they are active during the S phase of the cell cycle. Myelosuppression is the most common side effect, and irreversible toxicity may be seen with doses above 250 mg/m2.3

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