Dose escalation methods in phase I cancer clinical trials.
Dose escalation methods in phase I cancer clinical trials.
复制标题
DOI：
10.1093/jnci/djp079
复制
发表时间：
2009-05-20
期刊：
影响因子：
--
通讯作者：
Siu LL
中科院分区：
文献类型：
--
作者：
Le Tourneau C;Lee JJ;Siu LL
一期临床试验是开发抗癌药物的重要步骤。这些研究的主要目的是为II期试验确定新药或药物组合的推荐剂量和/或时间表。I期临床试验中剂量递增的指导原则是避免过多患者暴露于亚治疗剂量，同时保持安全性并保持快速累积。在这里，我们回顾了用于I期试验的剂量递增方法，包括基于规则和基于模型的剂量递增方法，这些方法已被开发用于评估新的抗癌药物。毒性传统上是涉及细胞毒性药物的I期试验的主要终点。然而，随着分子靶向抗癌药物的出现，描述最佳生物活性的潜在替代终点，如血浆药物浓度和肿瘤或替代组织中的靶标抑制，已被提出与新的试验设计一起。我们还描述了药物组合的特定方法，以及使用事件时间终点或毒性和有效性作为终点的方法。最后，我们介绍了各种剂量递增方法的优缺点，并讨论了这些方法在发育性肿瘤治疗中的具体应用。
Phase I clinical trials are an essential step in the development of anticancer drugs. The main goal of these studies is to establish the recommended dose and/or schedule of new drugs or drug combinations for phase II trials. The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual. Here we review dose escalation methods for phase I trials, including the rule-based and model-based dose escalation methods that have been developed to evaluate new anticancer agents. Toxicity has traditionally been the primary endpoint for phase I trials involving cytotoxic agents. However, with the emergence of molecularly targeted anticancer agents, potential alternative endpoints to delineate optimal biological activity, such as plasma drug concentration and target inhibition in tumor or surrogate tissues, have been proposed along with new trial designs. We also describe specific methods for drug combinations as well as methods that use a time-to-event endpoint or both toxicity and efficacy as endpoints. Finally, we present the advantages and drawbacks of the various dose escalation methods and discuss specific applications of the methods in developmental oncotherapeutics.
登录
查看更多内容
影响因子：
2.1
作者：
Bekele, B. Nebiyou;Ji, Yuan;Thall, Peter F.
通讯作者：
Thall, Peter F.
影响因子：
45.3
作者：
Baselga, J;Rischin, D;Albanell, J
通讯作者：
Albanell, J
影响因子：
2
作者：
GOODMAN, SN;ZAHURAK, ML;PIANTADOSI, S
通讯作者：
PIANTADOSI, S
影响因子：
45.3
作者：
Gordon, MS;Margolin, K;Adelman, DC
通讯作者：
Adelman, DC
影响因子：
0.9
作者：
Chu, Pei-Ling;Lin, Yong;Shih, Weichung Joe
通讯作者：
Shih, Weichung Joe