Phase I study of docetaxel dose escalation in combination with fixed weekly gemcitabine in patients with advanced malignancies

Purpose: To determine the maximum-tolerated dose of monthly docetaxel combi ned with fixed-dose weekly gemcitabine and describe the dose-limiting toxic ities (DLTs) of the combination. Patients and Methods: Patients with refractory solid tumors were treated wi th gemcitabine days 1, 8, and 15 every 4 weeks at a fixed dose of 800 mg/m( 2). Two docetaxel administration schedules were studied, with the drug admi nistered either day 1 or day 15 at doses of 45, 60, 75, and 100 mg/m(2) per cycle. Results: Forty patients received 132 cycles of chemotherapy On the day-1 sc hedule, the maximum-tolerated docetaxel dose was the highest planned dose o f 100 mg/m(2) with two DLT episodes among 12 patients treated with 34 cycle s at this dose level. On the day-15 schedule, delivery of the planned docet axel doses was not feasible because of thrombocytopenia and hepatic dysfunc tion. Hematologic toxicities included grade 4 neutropenia in 16 patients, w ith three episodes of febrile neutropenia; grades 3 to 4 thrombocytopenia i n nine patients; and anemia that required RBC transfusions in 10 patients. For patients treated at the highest docetaxel dose level, myelosuppression was not. dose limiting and only one of 34 cycles was complicated by febrile neutropenia, The most common nonhematologic toxicities were asthenia, flu- like symptoms, and fluid retention. Antineoplastic activity was noteworthy, with partial responses in nine of 21 patients with pretreated non-small-ce ll lung cancer (NSCLC; 43%; 95% confidence interval, 22 to 66), in four of seven patients with breast cancer, and in one patient with esophageal adeno carcinoma, Conclusion: Gemcitabine 800 mg/m(2) days 1, 8, and 15 can be safely combine d with docetaxel 100 mg/m(2) day 1 of a 28-day cycle. The observed antitumo r activity warrants phase II evaluation. (C) 1998 by American Society of Clinical Oncology