Schedules of Administration

Although the effects of various schedules are not always predictable, drugs that are rapidly metabolized, excreted, or both, especially if they are phase specific and thus act on only one portion of the cell cycle (e.g., cytarabine), appear to be more effective when administered by continuous infusion or frequent dose fraction-ation than by high-dose intermittent therapy. On the other hand, intermittent high-dose treatment of Burkitt's lymphoma with cyclophosphamide is more effective than fractionated treatment, since cyclophos-phamide acts on all phases of the cell cycle and almost all of the tumor cells in that disease are actively proliferating.

The classic example of schedule dependency is cytarabine, a drug that specifically inhibits DNA synthesis and is cytotoxic only to cells in S-phase. Continuous infusion or frequent administration of cytarabine hy-drochloride is superior to intermittent injection of the drug. Bleomycin is another drug for which continuous infusion may increase therapeutic efficacy.

Administration of some anticancer drugs by continuous infusion has been shown to improve their therapeutic index through selective reduction of toxicity with retained or enhanced antitumor efficacy.

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