THERAPEUTIC RESPONSE AND POTENTIAL PITFALLS IN PHASE-I CLINICAL-TRIALS OF ANTICANCER AGENTS CONDUCTED IN JAPAN

The published reports of phase I clinical trials of anticancer agents conducted in Japan from 1981 to 1991 were reviewed. A total of 56 clin ical studies that evaluated 38 different agents were reviewed. An aver age of five agents were studied each year. A total of 2200 patients ha d been recruited into the 56 clinical trials conducted during this per iod. A total of 91 patients (4.1%) responded to the treatment, with 23 showing a complete response (1.1%) and 48, a partial response (2.2%). In all, 62% of the responses were observed when patients were treated with doses ranging from 76% to 125% of the recommended doses for phas e II studies. The response rates obtained for hematological malignanci es were higher than those reported for other malignancies. The past st atus of phase I clinical trials in Japan can be summarized as follows. (1) A median of seven institutes participated in a single trial. The number of institutes participating correlated with the number of patie nts enrolled. However, too many institutes participated in a single ph ase I clinical trial in some studies. (2) The median duration of study for the clinical trials was 14 months. The duration of study was too long in some studies, considering the small number of patients enrolle d. In conclusion, the methodology of phase I clinical trials of antica ncer agents conducted in Japan should be improved in an efficient and scientific manner, especially for the testing of imported agents.