Multicenter Randomized Open-Label Phase III Study Comparing Efficacy, Safety, and Tolerability of Conventional Carboplatin Plus Etoposide Versus Dose-Intensified Carboplatin Plus Etoposide Plus Lenograstim in Small-Cell Lung Cancer in Extensive Disease Stage

Background: The combination of carboplatin and etoposide (CE) is one of the most effective regimens in the treatment of small-cell lung cancer (SCLC). The aim of this study was to investigate whether dose-intensified CE with the supplementation of granulocyte-colony-stimulating factor (G-CSF) is more effective than conventional CE in terms of survival with acceptable toxicity. Methods: In a 2-arm multicentric prospective open label study, adult patients with SCLC in extensive disease stage were randomized either to conventional CE (carboplatin AUC 5 on day 1 IV and etoposide 140 mg/m(2) IV on days 1-3, q28 days) or to dose-intensified therapy (carboplatin AUC 5 on day I IV and etoposide 190 mg/m(2) days 1-3 IV with lenograstim 263 F,g subcutaneously on days 4-13, q21 days). Primary end point was overall survival; secondary endpoints were toxicity, quality of life, and disease-free survival. Results: Seventy-nine patients were included. Thirty-seven received conventional CE and 42 received the dose-intensified regimen. Median survival in the conventional group and the dose-intensified group were 11.2 months [confidence interval (CI) 9.1-15.2] and 11.7 months (CI 8.8-14.7), respectively. Progression-free survival was 6.7 (CI 5.8-7.5) and 7.4 months (CI 6.2-9.0), respectively. There was no statistically significant difference between these groups. Grade 3/4 neutropenia occurred in 69.4% in the conventional arm versus 37.5% in the dose-intensified group (P = 0.009). Conclusion: Dose-intense CE with GM-CSF support can be administered safely but does not prolong overall or progression-free survival compared with standard therapy.