期刊
INVESTIGATIONAL NEW DRUGS
卷 30, 期 4, 页码 1493-1500出版社
SPRINGER
DOI: 10.1007/s10637-011-9682-9
关键词
PARP inhibitors; Olaparib; Topotecan; Targeted agents; Maximum tolerated dose; DNA repair
资金
- AstraZeneca
Background The aim of this phase I study was to determine the safety and tolerability and to establish the maximum tolerated dose (MTD) of orally administered olaparib (AZD2281) in combination with topotecan in patients with advanced solid tumors. Patients and methods Patients aged a parts per thousand yen18 years with histologically or cytologically diagnosed advanced solid tumors for whom no suitable effective therapy exists were included. Patients in four cohorts received topotecan (0.5 mg/m(2)/day x 3 days or 1.0 mg/m(2)/day x 3 days) intravenously in combination with oral olaparib 50, 100 or 200 mg bid for six cycles. The primary objectives were to determine the safety and tolerability and to establish the MTD of olaparib in combination with topotecan. Results Twenty-one patients were enrolled and 19 received treatment. Dose-limiting toxicities were neutropenia and thrombocytopenia. The MTD was established as topotecan 1.0 mg/m(2)/day x 3 days plus olaparib 100 mg bid. The most common adverse events (AEs) included fatigue and gastrointestinal events. There was an olaparib and topotecan dose-related increase in neutropenia which was dose limiting. Conclusions Further development of olaparib and topotecan in combination was not explored due to dose-limiting hematological AEs and the resulting sub-therapeutic MTD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据