Trends in the use and role of biomarkers in phase I oncology trials
Trends in the use and role of biomarkers in phase I oncology trials
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DOI：
10.1158/1078-0432.ccr-06-2860
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发表时间：
2007-11-15
影响因子：
11.5
通讯作者：
Chabner, Bruce A.
中科院分区：
文献类型：
--
作者：
Goulart, Bernardo H. L.;Clark, Jeffrey W.;Chabner, Bruce A.
目的：人们对使用生物标记物来帮助评估新的抗癌药物很感兴趣。我们评估了生物标记物的使用趋势及其对第一阶段试验主要目标的贡献。实验设计：我们对1991年至2002年提交给美国临床肿瘤学会年会的摘要以及与这些摘要相关的出版物进行了系统的综述。我们分析了生物标记物的使用及其对已发表的I期试验的贡献。结果：从1991年到2002年，美国临床肿瘤学会I期论文的20%(2458篇论文中的503篇)包含了生物标记物。这一比例随着时间的推移而增加(1991年为14%，而2002年为26%；P<；0.02)。生物标志物使用的独立预测因素包括国家癌症研究所的赞助、1999年至2002年期间的提交、成年人口和药物家族(生物制剂)。来自这些摘要的87项试验中，有11项(13%)的生物标志物支持II期研究的剂量选择。然而，在这87个试验中，除了一项(1%)外，11期剂量和时间表的主要决定因素是毒性和/或疗效。在87项已发表的试验中，有34项(39%)的生物标记物研究提供了支持所提出的作用机制的证据。结论：从1991年到2002年，生物标记物在I期试验中的使用有所增加。到目前为止，生物标记物的利用对剂量选择的贡献有限，主要是支持性的，剂量选择是第一阶段研究的主要终点。需要更多的研究来确定在I期试验中哪种类型的生物标记物信息最有价值。
Purpose: There has been interest in using biomarkers that aid the evaluation of new anticancer agents. We evaluated trends in the use of biomarkers and their contribution to the main goals of phase I trials. Experimental Design: We did a systematic review of abstracts submitted to the American Society of Clinical Oncology annual meeting from 1991 to 2002 and the publications related to these abstracts. We analyzed the use of biomarkers and their contribution to published phase I trials. Results: Twenty percent of American Society of Clinical Oncology phase I abstracts (503 of 2458) from 1991 to 2002 included biomarkers. This proportion increased over time (14% in 1991 compared with 26% in 2002; P < 0.02). Independent predictors of the use of biomarkers included National Cancer Institute sponsorship, submission in the time period of 1999 to 2002, adult population, and drug family (biological agents). Biomarkers supported dose selection for phase II studies in 11 of 87 of the trials (13%) emanating from these abstracts. However, the primary determinants of phase 11 dose and schedule were toxicity and/or efficacy in all but one of these 87 trials (1%). Biomarker studies provided evidence supporting the proposed mechanism of action in 34 of 87 of the published trials (39%). Conclusions: The use of biomarkers in phase I trials has increased over the period from 1991 to 2002. To date, biomarker utilization has made a limited and primarily supportive contribution to dose selection, the primary end point of phase I studies. Additional studies are needed to determine what type of biomarker information is most valuable to evaluate in phase I trials.