Chiorean, E. GabrielaPorter, Jennifer M.Foster, Anne E.Omari, Amal S.H. AlYoder, Christy A.Fife, Karen L.Strother, R. MatthewMurry, Daryl J.Yu, MenggangJones, David R.Sweeney, Christopher J.2020-12-162020-12-162008-02Chiorean, E. G., Porter, J. M., Foster, A. E., Al Omari, A. S., Yoder, C. A., Fife, K. L., ... & Sweeney, C. J. (2008). A phase I and pharmacokinetic trial of erlotinib in combination with weekly docetaxel in patients with taxane-naive malignancies. Clinical cancer research, 14(4), 1131-1137.https://hdl.handle.net/1805/24627Purpose: 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.en-USAttribution 4.0 InternationalPharmacokinetic TrialErlotinibWeekly DocetaxelArticle