Lessons Learned: Dose Selection of Small Molecule-Targeted Oncology Drugs

被引：42

作者：

Bullock, Julie M. ^{[1
]}

Rahman, Atiqur ^{[2
]}

Liu, Qi ^{[2
]}

机构：

[1] d3 Med LLC, Parsippany, NJ USA

[2] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20901 USA

来源：

CLINICAL CANCER RESEARCH | 2016年 / 22卷 / 11期

关键词：

EFFICACY; OPTIMIZATION; DESIGN; AGENTS;

D O I：

10.1158/1078-0432.CCR-15-2646

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Evaluation of dose plays a critical role in a successful oncology development program. Typically for oncology agents, the first-in-man phase I dose-escalation trials are conducted to determine a maximum tolerated dose (MTD). This MTD is taken forward into subsequent trials to establish the safety and efficacy of the drug product. Although this approach was appropriate historically for cytotoxics, the application of MTD as the recommend phase II dose has been problematic for the newer small molecule-targeted oncology agents. Promising alternative approaches using dose and exposure exploration, including lessons learned from recent targeted oncology agent development and approvals, are summarized and discussed.

引用

页码：2630 / 2638

页数：9