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A Phase I and Pharmacokinetic Trial of Erlotinib in Combination with Weekly Docetaxel in Patients with Taxane-Naive Malignancies

Authors' Affiliations: Departments of ¹ Medicine and ² Biostatistics, Indiana University, Indianapolis, Indiana and ³ University of Iowa College of Pharmacy, Iowa City, Iowa

Requests for reprints: Christopher J. Sweeney, Indiana University, 535 Barnhill Drive, Room 473, Indianapolis, IN 46202. Phone: 317-274-3515; E-mail: chsweene{at}iupui.edu.

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/m²) on days 1, 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 12 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/m² level (grade 3 enterocolitis). At 35 mg/m² docetaxel dose level, 6 of 10 patients required dose reductions to 30 mg/m² 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/m² docetaxel, repetitive dosing proved intolerable in a substantial number of patients; thus, the recommended phase II dose of weekly docetaxel is 30 mg/m² when combined with 150 mg of daily erlotinib.