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STUDY OBJECTIVES: Prospective randomized trials (PRTs) have suggested that third-generation agents (eg, gemcitabine, the taxanes, and vinorelbine) improve the survival time of patients with non-small cell lung cancer (NSCLC). However, < 30% of unselected NSCLC patients fulfill the eligibility criteria of such trials. We analyzed the outcomes of all consecutive and unselected patients with inoperable NSCLC in a single institution to determine whether there was an improvement in survival over time, and if so, to identify the factors that were associated with improved survival. METHODS: A total of 230 documented patients with NSCLC at the Basel University Hospital treated after 1990 were analyzed retrospectively. Break points by year of treatment were determined using sequential Cox proportional hazards regression models and the Kaplan-Meier estimator. Multivariate analysis was used to determine which factors were associated with improved survival over time. RESULTS: A marked improvement of survival was found since the introduction of the third-generation agents in 1997. The 1-year (40% vs 19%, respectively) and 2-year survival rates (23% vs 5%, respectively, p < 0.0001) of patients in whom NSCLC had been diagnosed since 1997 were significantly better than those prior to 1997. The two cohorts did not differ significantly in sex, stage, performance status, weight loss, and lactate dehydrogenase levels. The improvement since 1997 was due to better best supportive care (p < 0.025), better first-line chemotherapy (median overall survival [OS] time (9.2 vs 6.9 months, respectively; p < 0.0016), and better second-line chemotherapy (p < 0.0001). Finally, patients who received therapy with platinum plus a third-generation drug had significantly better outcomes than those who received an older therapy regimen (median OS time, 9.3 vs 6.7 months, respectively; p < 0.027). CONCLUSIONS: A significant improvement of survival in patients with NSCLC was observed in the last decade. The results of PRTs for palliative treatment of NSCLC seem to be applicable to an unselected group of patients with NSCLC, and therapeutic nihilism in the palliative setting seems not to be justified.