[Clinical pharmacology in development of new anticancer agents]

The role of clinical pharmacology in the development of new anticancer agents is discussed. In phase I studies, analysis of pharmacokinetic (PK) and pharmacodynamic (PD) relationship, in other words, the relationship among dose administered, pharmacological parameters and pharmacodynamic effects, is essential in the dose escalating process. In addition, we must pay careful attention to whether linearity between the dose administered and the pharmacological parameters is observed or not so as to assure a safe dose escalation strategy. Comparative analysis of the pharmacokinetics and pharmacodynamics between animal models and patients are also an important factor in safe dose escalation. A simple dose escalation strategy will be possible in such agents as the results of phase I are available in other countries. The concept of pharmacokinetic and/or pharmacodynamic drug interactions is essential in a combination phase I study, although this is not covered in the Good Clinical Practice (GCP) guideline. Pharmacological analysis should continue phase II studies to obtain a more accurate PK/PD relationship not only as to the side effects but also the clinical response, in order to analyze intra- or inter-patient variability in pharmacokinetics as well as pharmacodynamics. This would also be useful to establish population pharmacokinetic model or limited sampling strategy for phase III evaluation.