Phase I trial of weekly docetaxel and gemcitabine in patients with refractory malignancies

Abstract

BACKGROUND: A Phase I study using weekly docetaxel and gemcitabine was conducted to investigate toxicity; to determine the maximum tolerated dose (MTD) of each agent; and, in a preliminary fashion, to determine the antitumor activity of the combination. METHODS: Docetaxel and gemcitabine were administered intravenously on Days 1, 8, and 15 every 28 days. The dose levels of docetaxel and gemcitabine were as follows: Level I, docetaxel 20 mg/m(2)and gemcitabine 400 mg/m(2); Level II, docetaxel 30 mg/m(2)and gemcitabine 400 mg/m(2); Level III, docetaxel 30 mg/m(2)and gemcitabine 600 mg/m(2); Level IV, docetaxel 36 mg/m(2)and gemcitabine 600 mg/m(2); and Level V, docetaxel 36 mg/m(2)and gemcitabine 800 mg/m(2). RESULTS: Thirty-three eligible patients were entered. The diagnoses were as follows: Eleven patients had nonsmall cell lung carcinoma, 3 patients had carcinoma of the bladder, 3 patients had renal carcinoma, 2 patients had adrenal carcinoma, 5 patients had unknown primary tumors, and 9 patients had miscellaneous malignancies. Fifty-nine percent of patients had received prior chemotherapy. The median age was 62 years (range, 27-77 years), and the median Eastern Cooperative Oncology Group performance status was 1 (range, 0-1). Five patients were treated at Dose Levels I and II, 6 patients were treated at Dose Levels III and V, and 11 patients were treated at Dose Level IV. Grade 3-4 toxicities during Cycle I included neutropenia, thrombocytopenia, mucositis, and diarrhea. Dose-limiting toxicity, consisting of neutropenia and thrombocytopenia, occurred in three of six patients at Dose Level V. The combination of docetaxel 36 mg/m(2) and gemcitabine 600 mg/m(2) (Dose Level IV) was determined as the MTD and was the recommended Phase II dose. Two patients had a partial response: one patient with bladder carcinoma (Dose Level II) and one patient with nonsmall cell lung carcinoma (Dose Level III). CONCLUSIONS: Overall, weekly docetaxel and gemcitabine were well tolerated. Further studies using this combination are planned, including a Phase II trial in patients with advanced nonsmall cell lung carcinoma.