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PURPOSE: This meta-analysis was performed to compare the activity, efficacy and toxicity of platinum-based versus non-platinum-based chemotherapy in patients with advanced non-small-cell lung cancer. METHODS: Randomized phase II and III clinical trials comparing first-line palliative platinum-based chemotherapy with the same regimen without platinum or with platinum replaced by a nonplatinum agent were identified by electronic searches of Medline, Embase, and Cancerlit, and hand searches of relevant abstract books and reference lists. Response rates, 1-year survival, and toxicity were analyzed. Subgroups of trials using third-generation agents were compared. RESULTS: Thirty-seven assessable trials were identified including 7,633 patients. A 62% increase in the odds ratio (OR) for response was attributable to platinum-based therapy (OR, 1.62; 95% CI, 1.46 to 1.8; P < .0001). The 1-year survival rate was increased by 5% with platinum-based regimens (34% v 29%; OR, 1.21; 95% CI, 1.09 to 1.35; P = .0003). No statistically significant increase in 1-year survival was found when platinum therapies were compared to third-generation-based combination regimens (OR, 1.11; 95% CI, 0.96 to 1.28; P = .17). The toxicity of platinum-based regimens was significantly higher for hematologic toxicity, nephrotoxicity, and nausea and vomiting, but not for neurotoxicity, febrile neutropenia rate, or toxic death rate. CONCLUSION: Response is significantly higher with platinum-containing regimens. One-year survival was not significantly prolonged when platinum-based therapies were compared with third-generation-based combination regimens. Toxicity is generally higher for platinum-based regimens.