Combinations of vinorelbine with other nonplatinum agents show promising results in phase I and phase II trials in non-small cell lung cancer (NSCLC). In two phase II studies the efficacy and safety of vinorelbine/gemcitabine in patients with advanced NSCLC were assessed. In the first study, 32 chemotherapy-naive patients were treated with gemcitabine 1,250 mg/m2 and vinorelbine 25 mg/m2 on days 1 and 8 every 21 days The overall response rate was 25% (all partial responses) and median survival time was 8.3 months, with a 1-year survival rate of 38%; patients with performance status 0-1 had median survival of 11.7 months and a 1-year survival rate of 48%. In the second study, previously untreated and treated patients received gemcitabine/vinorelbine on days 1, 8, and 15 of a 28-day cycle. Because myelosuppression was observed in the first eight patients treated sequentially with 1,000 mg/m2 gemcitabine and 30 mg/m2 vinorelbine, the doses were subsequently reduced to 900 and 25 mg/m2, respectively. Of the 23 evaluable treatment-naive patients, in this preliminary analysis (presented at the 1999 American Society of Clinical Oncology meeting) 43% had partial responses, 31% had stable disease, and 22% experienced disease progression; estimated median survival was 11 months. Of 29 evaluable previously treated patients, 14% had partial responses, 28% had stable disease, and 41% experienced disease progression; estimated median survival was 9.2 months. Vinorelbine/gemcitabine is an active and well-tolerated regimen for patients with advanced NSCLC, with response and survival rates at least comparable to those with standard platinum-based regimens. Future directions for vinorelbine in the treatment of NSCLC include combinations with other agents and with radiation therapy in the treatment of locally advanced disease.