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Background: The objective of this study was to test the response rate and toxicity of alternating chemotherapy in previously untreated patients with extensive-stage small cell lung carcinoma (SCLC)., Methods: Patients with histologically proven, extensive-stage SCLC, with a performance status of 0-2, and who had received no prior chemotherapy were eligible. The design was a two-stage, Phase II, multicenter trial. Treatment consisted of alternating chemotherapy every 3 weeks with etoposide (100 mg/m(2) on Days 1-3) and cisplatin (30 mg/m(2) on Days 1-3) on Cycles 1, 3, 5 and with topotecan (1 mg/m(2) on Days 1-5) and paclitaxel (200 mg/m(2) on Day 5) on Cycles 2, 4, and 6. Filgrastim support was given with Cycles 2, 4, 6., Results: Forty-four patients were eligible and evaluable. The primary toxicity was myelosuppression. The median absolute neutrophil count was 300/microL with 70% Grade 4 neutropenia. The median platelet count was 58,000/microL with 23% Grade 4 thrombocytopenia. Grade 4 nonhematologic toxicities occurred in 16% of patients. Overall toxicities were not different between the two regimens. There were no treatment-related deaths. Complete or partial responses occurred in 34 patients (77%). The median time to progression was 6.9 months, with a median survival of 10.5 months and with 1-year and 2-year survival rates of 37% and 12%, respectively., Conclusions: The regimen of alternating chemotherapy was associated with substantial myelosuppression and resulted in a high response rate and good overall survival. The results were similar to those reported in prior trials and did not suggest any improvement in therapy for patients with SCLC., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11377)