Controversies in the treatment of advanced stages of small cell lung cancer.

Small cell lung cancer is a highly proliferative tumor with the potential of early hematogeneous spread. At the time of first diagnosis more than 80% of patients present with distant metastases. Although response rate to chemotherapy is high with > 50% confirmed objective responses, the majority of patients relapse within several months after first-line chemotherapy. The combination of cisplatin plus etoposide has become standard chemotherapy. In contrast to early stages, equal efficacy of cisplatin and carboplatin in combination with etoposide has been suggested in advanced disease in two randomized trials in the 1990s. Newer agents like the topoisomerase I inhibitors topotecan and irinotecan have been investigated for first line treatment. Two phase III studies demonstrated similar efficacy of topotecan when compared to etoposide. Results of first line therapy with irinotecan are more contradictory. A first trial demonstrated superiority of irinotecan/cisplatin over etoposide/cisplatin in a Japanese population. However, two subsequent North American phase III trials showed equivalent efficacy. Recently a Scandinavian phase III trial found superiority of irinotecan/carboplatin over etoposide/carboplatin. Prophylactic cranial irradiation (PCI) after first line chemotherapy has become standard of care in advanced stages, because a randomized phase III trial of the EORTC demonstrated a survival benefit. Second-line therapy in relapsed disease improves survival. A randomized trial showed similar efficacy of topotecan when compared to anthracyline containing chemotherapy, with an improvement of cancer related symptoms in the topotecan arm.