Little progress has been made in the treatment of small cell lung cancer over the past two decades. Superiority of combined irinotecan-cisplatin over standard etoposide-cisplatin in a Japanese phase III trial was not confirmed in two subsequent US studies. In this Practice Point we discuss a randomized, phase III trial by Hermes and colleagues, which included 220 patients with extensive-disease small cell lung cancer and showed superiority of carboplatin-irinotecan versus carboplatin-oral etoposide. In this trial, 47% of patients had a performance status > or = 3 and 35% were older than 70 years, which represents a typical clinical practice population of patients; however, oral administration of etoposide and an arbitrary dose reduction in elderly and unfit patients represent limitations of the study. A European trial of irinotecan-carboplatin versus intravenous etoposide-carboplatin has completed accrual and results will be analyzed in 2009. Although the results of the study by Hermes et al. are of interest, substitution of etoposide by irinotecan can not be recommended.