Chemotherapy administration: doses, infusions and choice of schedule.

Oncologists are trained to make the best use of all available modes of therapy for patients with cancer. Our current armamentarium of cytotoxic drugs is, however, far from ideal, resulting in therapeutic failure in some of the common solid tumours. To make the best use of available drugs, optimum doses, schedules and routes of administration should be used for each individual patient and disease state. Existing drugs: Traditional methods of drug development have produced some active anticancer drugs, though the inflexibility and empiricism evident in the early-phase clinical trials of some drugs has seriously delayed the definition of optimum doses, schedules and routes of administration. This is illustrated by the anticancer agents, etoposide and 5-fluorouracil, both of which are still not used optimally, despite more than 20 years of clinical investigation. New drugs: It could be argued that these drugs were developed prior to our improved understanding of drug actions, pharmacokinetics and pharmacodynamics, and that such problems do not arise with new agents today. However, examples of the camptothecin derivatives (topotecan and CPT-II) show that we have progressed, but that we still have a long way to travel. This paper highlights the problems inherent in the development of new anticancer drugs. Strategies for avoiding these problems include: adoption of biological endpoints for phase I studies; the use of modern pharmacokinetic techniques to develop pharmacodynamic models; adaptive control of drug dosing.