Response rates, duration of response, and dose response effects in phase I studies of antineoplastics.
Over a period of 14 years, 7,960 patients were treated in 228 phase I trials. In these patients, there were 75 complete and 432 partial responses for an overall objective response rate of 6%. Complete responses lasted a median of six months (range 1-18), while partial responses lasted a median of three months (range 1-17). Of note is that no drug has made it to the market which has not had a response in phase I trials. Responses were noted in very diverse histologic types of tumors. Although there were responses at doses which were as low as 3-5% of the recommended dose for phase II trials, the majority of responses did occur at 80-120% of the dose recommended for phase II trials. Although the response rate in phase I trials is indeed low, responses do occur. This response rate information should help the clinician provide facts for the patient considering a phase I trial with new anticancer agents. These findings also emphasize that although phase I trials are characteristically dose-finding studies, if no responses are noted in phase I studies, it is unlikely the drug will be used routinely in the clinic.
Von Hoff
D D
DD
University of Texas, Health Science Center, San Antonio 78284.
Turner
J
J
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D006801:Humans; D015201:Meta-Analysis as Topic; D009369:Neoplasms / Q000188:drug therapy; D011379:Prognosis
D000970:Antineoplastic Agents