Phase II trial of docetaxel and vinorelbine in patients with advanced non-small-cell lung cancer

Purpose: Docetaxel and vinorelbine are active agents in advanced non-small- cell lung cancer (NSCLC) and demonstrate preclinical synergism perhaps, in part, through their inactivation of the proto-oncogene bcl-2. We show that docetaxel (60 mg/m(2)) and vinorelbine (45 mg/m(2)) can be safely combined when given on an every 2-week schedule with filgrastim, with encouraging an titumor activity observed. Patients and Methods: Thirty-five chemotherapy naive patients with advanced NSCLC received vinorelbine as an intravenous push immediately followed by docetaxel as a I-hour intravenous infusion once every 2 weeks. Prophylactic corticosteroids, ciprofloxacin, and filgrastim were used. Results: We delivered median doses of 450 mg/m(2) of vinorelbine and 600 mg /m(2) of docetaxel, The major objective response rate was 51% (95% confiden ce interval [CI], 34% to 68%). With a median follow-up of 14 months, the pr edicted median survival time wets 14 months, and the I-year survival rate w as 60% (95% CI, 44% to 80%). Febrile neutropenia occurred in five patients and five (1.3%) of 384 treatments. No dose-limiting neurotoxicity occurred. Symptomatic onycholysis and excessive lacrimation were observed after seve ral months or more of therapy. Conclusion: Docetaxel 60 mg/m(2) and vinorelbine 45 mg/m(2), both given eve ry 2 weeks, is ct highly active combination for the treatment of advanced N SCLC. Filgrastim largely obviates neutropenic fever and allows for the sing le-agent dose-intensity of both drugs to be delivered. The occurrence of ce rtain late toxicities can limit use in some cases and suggests that the com bination could also be beneficial in settings requiring briefer, fixed peri ods of treatment, such as in induction or postoperative therapy. (C) 2000 b y American Society of Clinical Oncology.