Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: Results of a phase II trial

BACKGROUND. Single-agent gemcitabine and vinorelbine have activity in treatment of patients with soft-tissue sarcomas. The combination of gemcitabine plus vinorelbine has activity against several forms of metastatic carcinoma with acceptable toxicity. This study evaluated the efficacy and tolerability of gemcitabine plus vinorelbine in advanced soft-tissue sarcoma. METHODS. A single academic center performed this phase II trial. Eligible patients had unresectable or metastatic soft-tissue sarcomas, Eastern Cooperative Group performance status of 0-2, adequate organ function, and ≤1 prior regimen. Gemcitabine 800 mg/m² was given over 90 minutes on Days 1 and 8 of a 21-day cycle after administration of vinorelbine 25 mg/m². Dosing schedule was modified for toxicity (doses constant but administered on Days 1 and 15 of a 28-day cycle). Dose reductions were allowed if unacceptable toxicities recurred. RESULTS. The study accrued 40 patients, and 248 dosing cycles were administered (range, 1-32). No treatment-related deaths occurred. Of 9 episodes of grade 4 toxicities, 8 were hematologic. Of 38 episodes of grade 3 toxicity, 24 were hematologic. Clinical benefit was seen in 25% of patients and was defined as complete response (CR), partial response (PR), or stable disease (SD) at >4 months. There has been 1 CR lasting >1 year in a patient with high-grade pleomorphic spindle-cell sarcoma. CONCLUSIONS. Gemcitabine given by a fixed-dose rate of infusion combined with vinorelbine was associated with clinically meaningful rates of disease control in patients with advanced soft-tissue sarcoma. Toxicity was acceptable. This study contributed to data that have supported the administration of fixed-dose rate gemcitabine-based drug regimens in soft-tissue sarcomas.