The impact of drug administration sequence and pharmacokinetic interaction in a phase I study of the combination of docetaxel and gemcitabine in patients with advanced solid tumors
作者:
H Dumez,
M Louwerens,
A Pawinsky,
ASTh Planting,
MJA de Jonge,
AT Van Oosterom,
M Highley,
G Guetens,
M Mantel,
G De Boeck,
E de Bruijn,
J Verweij,
期刊:
Anti-Cancer Drugs
(OVID Available online 2002)
卷期:
Volume 13,
issue 6
页码: 583-593
ISSN:0959-4973
年代: 2002
出版商: OVID
关键词: Gemzar;Taxotere;therapeutic drug monitoring;toxicity
数据来源: OVID
摘要:
Our objective was to determine the maximum tolerated dose (MTD) of two administration sequences of docetaxel and gemcitabine in cancer patients, and to describe the pharmacokinetics of both drugs. Patients were treated in a 4-weekly schedule at two dose levels: gemcitabine 800 mg/m2on days 1, 8 and 15, and docetaxel 85 or 100 mg/m2on day 15 (levels I and II). The protocol was amended to a 3-weekly schedule, testing gemcitabine 800 or 1000 mg/m2on days 1 and 8, with docetaxel 85 mg/m2on day 8 given initially (dose levels IIIa and IV). At the recommended dose, an extra cohort of patients initially received gemcitabine (dose level IIIb). Eleven patients were treated with the 4-week schedule; 29% of cycles were delayed predominantly because of hematological toxicity. Four patients developed dose-limiting toxicities (DLTs), predominantly hematological. In the 3-week schedule, 14 patients were treated. At level IV, three of four patients developed DLTs, defining the MTD. With the reverse sequence, three patients received a total of 10 cycles. Overall, nine partial remissions were observed. We conclude the recommended dose for phase II studies is gemcitabine 800 mg/m2on days 1 and 8, combined with docetaxel 85 mg/m2on day 8, on a 3-weekly schedule. Gemcitabine distribution is significantly altered upon docetaxel administration.
点击下载:
PDF
(142KB)
返 回