4.4 Article

Phase Ia study of a hypoxic cell sensitizer doranidazole (PR-350) in combination with conventional radiotherapy

期刊

ANTI-CANCER DRUGS
卷 12, 期 1, 页码 1-6

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00001813-200101000-00001

关键词

doranidazole; hypoxic cell sensitizer; phase I; radiosensitizer

向作者/读者索取更多资源

A phase la study of a 5-nitroimidazole nucleoside analog radiosensitizer doranidazole was conducted to evaluate its toxicity and pharmacokinetics in patients undergoing conventional external beam radiotherapy. Twenty-nine patients, aged 40-74 years, with a WHO performance status of 0-2 and with adequate organ functions, were entered in the study. Single administration of doranidazole was investigated first with 13 patients and then a course of five consecutive daily administrations was tested In 16 patients. Doranidazole was given I.v. 25 min before irradiation. Doranidazole doses of 400, 800, 1300 and 2000 mg/m(2) were evaluated in the former study, and daily doses of 800, 1300 and 2000 mg/m(2) were investigated in the latter study. All patients tolerated doranidazole administration. Although a transient decrease in the 24-h creatinine clearance rate was observed in five patients tone in the single administration study and four in the repeat administration study), this was not considered to be the dose-limiting toxicity. Other toxicities (hematological and gastrointestinal), which may not be related to doranidazole administration, were also mild and were not dose limiting. No neurotoxicity was observed. The average maximum concentration, area under the time-concentration curve and half-life of doranidazole in serum were 172-194 mug/ml, 502-582 mug.h/l and 4.2-4.6 h, respectively, at 2000 mg/m2. At the tested doses, administration of doranidaozle was tolerable and achieved serum concentrations at which reasonable radiosensitization could be expected. A phase Ib/II study to evaluate the feasibility and efficacy of up to 30 repeat administrations seems to be warranted. [(C) 2001 Lippincott Williams & Wilkins.].

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。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据