A phase I and pharmacokinetic trial of erlotinib in combination with weekly docetaxel in patients with taxane-naive malignancies

被引:20
作者
Chiorean, E. Gabriela [1 ]
Porter, Jennifer M. [1 ]
Foster, Anne E. [1 ]
Al Omari, Amal S. H.
Yoder, Christy A. [1 ]
Fife, Karen L. [1 ]
Strother, R. Matthew [1 ]
Murry, Daryl J. [3 ]
Yu, Menggang [2 ]
Jones, David R.
Sweeney, ChristopherJ. [1 ]
机构
[1] Indiana Univ, Dept Med, Indianapolis, IN 46202 USA
[2] Indiana Univ, Dept Biostat, Indianapolis, IN 46204 USA
[3] Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA
关键词
D O I
10.1158/1078-0432.CCR-07-0437
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: This study aimed to define the maximum tolerated dose of weekly docetaxel combined with daily erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor. Experimental Design: Patients with any solid tumor received 150 mg erlotinib with escalating doses of docetaxel (20, 25, 30, and 35 mg/m(2)) on days1, 8, and 15 every 28 days. The pharmacokinetics of docetaxel and erlotinib was determined on cycle 2, day 1. Erlotinib was given for a maximum of U cycles and docetaxel was given for up to 6 cycles. Results: Twenty-five patients (17 males and 8 females) were enrolled with a median age of 56 years (range, 34-76); Eastern Cooperative Oncology Group performance status of 0/1 was 20/5. One patient had a dose-limiting toxicity in cycle 1 at the 25 mg/m(2) level (grade 3 enterocolitis). At 35 mg/m(2) clocetaxel dose level, 6 of 10 patients required dose reductions to 30 mg/m(2) beyond cycle 1 due to neutropenia (3 patients) and mucositis, increased bilirubin, and diarrhea (1 patient each). The clearance of docetaxel and erlotinib of 61.7 and 8.16 L/h, respectively, did not seem to differ from historical controls. Responses were seen in non-small cell lung cancer, prostate cancer, and hepatobiliary cancers, including a complete response lasting 36+ months in a patient with hepatocellular carcinoma. Conclusion: Although no maximum tolerated dose was reached in cycle 1 with 35 mg/m(2) clocetaxel, repetitive dosing proved intolerable in a substantial number of patients; thus, the recommended phase II dose of weekly docetaxel is 30 mg/m(2) when combined with 150 mg of daily erlotinib.
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收藏
页码:1131 / 1137
页数:7
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