BACKGROUND A randomized phase II trial was conducted to determine if two non-platinum protocols are able to yield a similar efficacy and toxicity profile as compared to two platinum-based doublets in advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS A total of 61 patients were randomly assigned to a reference regimen of carboplatin and paclitaxel (repeated every 3 weeks) or to one of three experimental regimens: paclitaxel plus vinorelbine (repeated every 3 or 4 weeks) and carboplatin plus paclitaxel (repeated every 4 weeks). RESULTS The objective remission rate for all the patients was 34.1%. The median progression-free survival for all the patients was 3 months. The median overall survival and one-year overall survival were 6 months and 21.5%, respectively. Toxicity was moderate and manageable. Response, survival and toxicity did not significantly differ between the four treatment groups. CONCLUSION The efficacy and toxicity profile of platinum-free combinations is comparable to that of platinum-based doublets.