Von Hoff D D, Turner J
University of Texas, Health Science Center, San Antonio 78284.
Invest New Drugs. 1991 Feb;9(1):115-22. doi: 10.1007/BF00194562.
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.
在14年的时间里,228项I期试验共治疗了7960例患者。这些患者中,有75例完全缓解和432例部分缓解,总体客观缓解率为6%。完全缓解持续的中位时间为6个月(范围1 - 18个月),而部分缓解持续的中位时间为3个月(范围1 - 17个月)。值得注意的是,没有一种在I期试验中没有反应的药物能够上市。在非常多样的肿瘤组织学类型中都观察到了反应。虽然在低至II期试验推荐剂量3 - 5%的剂量下也有反应,但大多数反应确实发生在II期试验推荐剂量的80 - 120%。虽然I期试验中的缓解率确实很低,但反应确实会出现。这种缓解率信息应该有助于临床医生为考虑使用新型抗癌药物进行I期试验的患者提供事实依据。这些发现还强调,虽然I期试验的典型特征是剂量探索研究,但如果在I期研究中未观察到反应,该药物不太可能在临床上常规使用。