OBJECTIVES: A prospective randomised controlled Phase III clinical trial demonstrated that three platinum-based chemotherapeutic regimens with novel agents - gemcitabine/cisplatin (Gem/Cis), paclitaxel/carboplatin (Pac/Carbo) and vinorelbine/cisplatin (Vin/Cis) - had comparable efficacy in chemotherapy-naive Italian patients with advanced non-small cell lung cancer (NSCLC): median survival times ranged from 9.5 to 9.9 months and median time to progression ranged from 4.6 to 5.5 months (Scagliotti et al. 2002). As part of the Gemzar Retrospective Economic Analysis of clinical Trials (GREAT2), we performed a retrospective cost comparison of these three chemotherapeutic regimens from the perspective of the Italian health care system. METHODS: The analysis involved costing of chemotherapy and medical resource utilisation collected prospectively during the trial published by Scagliotti et al. (2002). Direct costs were compared from four resource categories: chemotherapy acquisition, drug administration, hospitalisation associated with adverse events, and other medical resources. Italian health care unit costs were obtained from published sources. RESULTS: Lowest treatment costs were incurred by the Gem/Cis group (8,092€), followed by the Vin/Cis and Pac/Carbo groups (9,320€ and 11,203€ respectively). The cost difference between the Gem/Cis and Pac/Carbo regimens was due to the difference in chemotherapy acquisition costs (3,732€), which offset the increased costs for drug administration (499€) and other medical resources (524€) in the Gem/Cis group. The overall per-patient cost saving for Gem/Cis versus Vin/Cis (1,227€) was primarily due to reduced hospitalisations for adverse events (2,223€) despite the increased acquisition costs for Gem/Cis (1,422€). CONCLUSIONS: Based on data collected during a randomised clinical trial, first-line use of Gem/Cis offers potential cost savings compared to other platinum-based third-generation agent combinations in the treatment of advanced NSCLC in Italy. Since these savings relate primarily to chemotherapy acquisition and hospitalisation costs due to adverse events, they are likely to be transferred to the community setting.