Risks and benefits of phase 1 oncology trials, 1991 through 2002
Risks and benefits of phase 1 oncology trials, 1991 through 2002
复制标题
DOI：
10.1056/nejmsa042220
复制
发表时间：
2005-03-03
影响因子：
158.5
通讯作者：
Grady, C
中科院分区：
文献类型：
--
作者：
Horstmann, E;McCabe, MS;Grady, C
先前对1期肿瘤学试验的回顾报告说，对治疗的反应率为4%至6%，与毒性相关的死亡率为0.5%。这些结果可能不反映率在目前的1期肿瘤学trials.METHODSWe审查了所有非儿科1期肿瘤学试验赞助的癌症治疗评价计划在美国国家癌症研究所1991年和2002年之间。我们报告了治疗反应率、病情稳定率、4级毒性事件率和治疗相关死亡率。我们分析了460项试验，涉及11，935名参与者，所有参与者都进行了毒性评估，其中10，402人进行了治疗反应评估。总体响应率（即，完全和部分反应）为10.6%，试验之间存在相当大的差异。单一研究性化疗药物的“经典”1期试验仅占试验的20%，反应率为4.4%。包括至少一种由食品和药物管理局批准的抗癌药物的研究占试验的46.3%，应答率为17.8%。另有34.1%的参与者病情稳定或部分缓解。中毒事件导致的总死亡率为0.49%。在3465名参与者中，有14.3%的参与者至少有一次4级毒性事件的发作。CONCLUSIONSOverall反应率1期肿瘤学试验高于以前报道的，虽然他们没有改变经典的1期试验，毒性相关的死亡率保持稳定。然而，在不同类型的1期肿瘤学试验中，反应率和毒性反应率各不相同。
BACKGROUNDPrevious reviews of phase 1 oncology trials reported a rate of response to treatment of 4 to 6 percent and a toxicity-related death rate of 0.5 percent. These results may not reflect the rates in current phase 1 oncology trials.METHODSWe reviewed all nonpediatric phase 1 oncology trials sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute between 1991 and 2002. We report the rates of response to treatment, of stable disease, of grade 4 toxic events, and of treatment-related deaths.RESULTSWe analyzed 460 trials involving 11,935 participants, all of whom were assessed for toxicity and 10,402 of whom were assessed for a response to therapy. The overall response rate (i.e., for both complete and partial responses) was 10.6 percent, with considerable variation among trials. ``Classic'' phase 1 trials of single investigational chemotherapeutic agents represented only 20 percent of the trials and had a response rate of 4.4 percent. Studies that included at least one anticancer agent approved by the Food and Drug Administration constituted 46.3 percent of the trials and had a response rate of 17.8. An additional 34.1 percent of participants had stable disease or a less-than-partial response. The overall rate of death due to toxic events was 0.49 percent. Of 3465 participants for whom data on patient-specific grade 4 toxic events were available, 14.3 percent had had at least one episode of grade 4 toxic events.CONCLUSIONSOverall response rates among phase 1 oncology trials are higher than previously reported, although they have not changed for classic phase 1 trials, and toxicity-related death rates have remained stable. Rates of response and toxicity vary, however, among the various types of phase 1 oncology trials.