The practical benefits of pharmacokinetics in the use of antineoplastic agents

Clinical pharmacokinetics has clearly had an important impact on the use of antineoplastic agents, but this influence has primarily been the result of comprehensive analyses conducted at the time of initial clinical trial. Such studies have often determined the dose, schedule, and route of administration, and have provided general guidelines for dose adjustment in patients with organ dysfunction. On the other hand, routine pharmacokinetic monitoring, while a highly effective adjunct to drug therapy in clinical specialties other than cancer, has not yet had an important effect on clinical oncology, with the obvious exception of high-dose methotrexate therapy. A number of potentially important applications of routine monitoring are pointed out in this paper, and will certainly be examined in the future as a means of dealing with pharmacokinetic variability. However, major impediments in this effort are posed by complexity of antineoplastic pharmacology and the lack of suitably sensitive, specific, and rapid assays for routine clinical use. Radioimmunoassays and competitive binding methods offer considerable hope in this effort, but the widespread application of these methods has not yet been realized in clinical practice.