Background: Randomized trials in extensive disease (ED) small cell lung cancer (SCLC) comparing the camptothecins to standard etoposide based chemotherapy have reached conflicting results. Here we report the results of an interim analysis of a phase III trial randomly allocating patients (pts) with ED SCLC to etoposide or topotecan in combination with platinum. Methods: Previously untreated pts with ED SCLC were randomized to six cycles of T (topotecan 2.0 mg/m² IV, day 1-3; cisplatin 50 mg/m² IV, day 3) or E (etoposide 120 mg/m², day 1-3; carboplatin IV AUC = 5, day 1) every 3 weeks. Primary end-point was overall survival (OS) and secondary end-points were response, progression-free survival (PFS), and safety. A sample size of 380 pts was estimated to detect an increase in 2-year survival from 7.5 to 15 % (α=0.05, β=0.20.) ClinicalTrials.gov NCT 00812266. Results: The trial was prematurely stopped due to poor accrual according to a pre-planned interim analysis after the accrual of 281 pts reducing power to 0.66. Prognostic factors were equally balanced between arms. WHO performance status > 2 were recorded in 20.0% and 50% were females. Median age was 64 years (40 – 82). Most frequent grade 3/4 non-hematological adverse events (AEs) were infections (E 17.1 vs T 12.1%) and fatigue (E 14.2 vs T 12.7%). Most common grade 1/2 non-hematological AEs were alopecia (E 91.3 vs T 88.0%), nausea (E 55.9 vs T 57.9%) vomiting (E 27.6 vs T 24.1%), auditory toxicity (E 25.2 vs T 33.8%), and neuropathy (E 33.9 vs T 39.8%). Grade 4 leuco- and thrombocytopenia were observed in 21.1 and 12.8% of pts in arm E, respectively, compared to 6.7 and 5.2% in arm T (p < 0.01). Overall response rates were 69.1 % in arm E compared to 59.8% in arm T (NS). Median PFS was 6.6 months in E arm and 6.9 month in arm T, HR = 0.93, 95% CI 0.72-1.19, p=0.55. Median OS and 2-yr survival rates were 10.9 months and 9.2% in arm T, compared to 9.8 months and 8.7% in arm E, respectively, HR = 0.87, 95% CI 0.67-1.17, p=0.26. Conclusions: No differences in OS or PFS were observed comparing first line E with T in ED SCLC. Significantly more hematological toxicity was noted in the E arm. A biomarker study is planned to identify pts that derive most benefit from either T or E. Clinical trial information: NCT00812266.