Clinical pharmacology of anticancer drugs has made significant progress in the last two decades and plays an important role in drug development, clinical study design, and in the rational use of cancer chemotherapy. Among the important factors contributing to the integration of clinical pharmacology into cancer chemotherapy was the introduction of highly sensitive and specific analytical methods for the determination of the drugs and their metabolites in the physiological fluids and the tumor tissues. In the Phase I clinical studies elucidation of pharmacokinetic variables such as absorption, distribution metabolism and excretion (ADME) contribute to the rational design of dose schedule, escalation procedure and better understanding of drug related toxicities. The elucidation of the major elimination routes enables recommendation of the dose adjustments in patients with impaired renal or liver functions. In the clinical pharmacodynamics the biochemical studies have the potential for elucidation and prevention of dose limiting toxicities and enhancement of the antitumor effect. Despite the progress achieved clinical pharmacokinetics of anticancer drugs fall behind other classes of drugs where routine monitoring of drug levels has become a part of regular treatment. With the exception of methotrexate, where plasma level monitoring is required for its use in the high dose regimen routine plasma level monitoring has not yet been found clinically useful for the majority of anticancer drugs. Rapid progress in the analytical methodology and emphasis on the clinical pharmacokinetic studies should lead to further enhancement of the role of clinical pharmacology in cancer chemotherapy, particularly in the treatment of individual patients.
The role of clinical pharmacology in cancer chemotherapy
