Horstmann Elizabeth, McCabe Mary S, Grochow Louise, Yamamoto Seiichiro, Rubinstein Larry, Budd Troy, Shoemaker Dale, Emanuel Ezekiel J, Grady Christine
Department of Clinical Bioethics, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Md 20892-1156, USA.
N Engl J Med. 2005 Mar 3;352(9):895-904. doi: 10.1056/NEJMsa042220.
Previous 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.
We 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.
We 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.
Overall 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.
先前对1期肿瘤学试验的综述报告称，治疗缓解率为4%至6%，毒性相关死亡率为0.5%。这些结果可能无法反映当前1期肿瘤学试验中的发生率。
我们回顾了1991年至2002年间由美国国立癌症研究所癌症治疗评估项目赞助的所有非儿科1期肿瘤学试验。我们报告了治疗缓解率、疾病稳定率、4级毒性事件发生率和治疗相关死亡率。
我们分析了460项试验，涉及11935名参与者，所有参与者均接受了毒性评估，其中10402名接受了治疗反应评估。总体缓解率（即完全缓解和部分缓解）为10.6%，各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%，缓解率为4.4%。至少包含一种美国食品药品监督管理局批准的抗癌药物的研究占试验的46.3%，缓解率为17.8%。另外34.1%的参与者疾病稳定或缓解程度低于部分缓解。毒性事件导致的总体死亡率为0.49%。在有患者特异性4级毒性事件数据的3465名参与者中，14.3%至少发生过一次4级毒性事件。
1期肿瘤学试验的总体缓解率高于先前报告的水平，尽管经典1期试验的缓解率没有变化，且毒性相关死亡率保持稳定。然而，不同类型的1期肿瘤学试验的缓解率和毒性存在差异。
