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

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 1, 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.