Pharmacologically based phase I trials in cancer chemotherapy.

Recent developments in Phase I trial methodology are reviewed. Preclinical pharmacological studies can be used in Phase I trials to improve patient selection, starting dose identification, and dose escalation. Establishing pharmacokinetic-pharmacodynamic relationships is also an important new aspect of Phase I trial methodology; these relationships can be exploited in subsequent efficacy studies. Finally, the inclusion of molecular pharmacodynamic studies in Phase I trials is increasing with a view to identifying the mechanism of action of a new agent in patients.