[Current status of phase I and phase II trials--experience in Habikino from 1988 to 1994]

Introduction of a new agent in the treatment for cancer will require usually three phases of investigation. A new drug will be tested in a small series of patients for toxicity and feasibility; the main objective of a phase I trial is to determine the maximum tolerated dose with a specific type of administration. Demonstration of activity is the major goal of phase II trials, which will place some confidence interval on the efficacy of the new agent. Information obtained from phase I and II studies should be the basis for phase III trials. Based upon our experience with the clinical development of CPT-11, this paper reviews the two factors which influence the quality of the phase I and II trials. Firstly, adequately designed and prepared plans for every clinical trial are essential minimum requirement. Another issue which has been frequently overlooked has been variation from the planned protocol treatment. Such variations can be due to the intolerance of the patient to toxicity as well as the individual physician's poor perceptions and the physician's intolerance of toxicity.