Docetaxel combined with vinorelbine: phase I results and new study designs.

This was a phase I dose-finding and pharmacokinetic study of vinorelbine (Navelbine) and docetaxel (Taxotere) as first-line chemotherapy for metastatic breast cancer. Vinorelbine dose, 20 or 22.5 mg/m2, on days 1 and 5, was followed on day 1 by docetaxel every 21 days, in doses increasing from 60 to 100 mg/m2. Two maximum tolerated doses were reached, the first at 75 mg/m2 of docetaxel and 22.5 mg/m2 of vinorelbine, and the second at 100 mg/m2 of docetaxel and 20 mg/m2 of vinorelbine. Symptomatic peripheral neuropathy was not observed. The recommended doses for phase II studies are 75 to 85 mg/m2 of docetaxel on day 1 and 20 mg/m2 of vinorelbine on days 1 and 5, every 3 weeks. The treatment regimen, which included 3-day corticosteroid prophylaxis, resulted in only mild fluid retention. Responses were seen at all dose levels, with an 80% overall response rate at the higher recommended dose; the overall response rate for patients at all dose levels was 66%. A high rate of response, including a complete response, was observed in patients with liver metastases.