09O6-苄基鸟嘌呤和 BCNU——生化调节试验-猫眼课题宝

09O6-苄基鸟嘌呤和 BCNU——生化调节试验

批准号：

6305441

负责人：

TIMOTHY P SPIRO

金额：

$1.92万

依托单位：

CASE WESTERN RESERVE UNIVERSITY

依托单位国家：

美国

项目类别：

财政年份：

1999

资助国家：

美国

项目状态：

已结题

起止时间：

1999-12-01 至 2000-11-30

来源：

https://reporter.nih.gov/project-details/6305441

关键词：

antineoplastics carmustine clinical research clinical trial phase I combination cancer therapy dosage drug adverse effect drug screening /evaluation guanine human subject human therapy evaluation

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英文摘要

Early phase evaluation of anticancer drugs has traditionally used toxicity (usually hematological) rather than efficacy end points to establish appropriate dosing schedules. To establish a biochemical efficacy end point for overcoming alkylguanine DNA alkyltransferase (AGT)-mediated tumor cell resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea, we performed a novel dose escalation clinical trial for the AGT-depleting agent 06-benzylguanine (BG). The dose of BG required to deplete AGT to undetectable levels (BMD(T) in sequential computed tomography-guided tumor tissue biopsies before BG and 18 h after BG was determined. Thirty patients received doses of BG ranging from 10 to 120 mg/m2 on the GCRC.

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