Advances in the treatment of small-cell lung cancer.

Small-cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastatic dissemination and responsiveness to initial therapy. The incidence of SCLC has been declining over the past decade, mainly due to a decreased incidence in men. Positron-emission tomographic (PET) scans appear to improve the accuracy of staging and treatment planning in patients with SCLC. Limited-stage (LS) SCLC is a potentially curable disease, with long-term survival of ~20% when treated with platinum-based chemotherapy plus concurrent thoracic radiation. Hyperfractionated thoracic radiation and prophylactic cranial irradiation (PCI) may significantly improve overall survival in selected patients with LS-SCLC. For patients with extensive-stage (ES) SCLC, survival can be increased with combination chemotherapy, but the disease remains incurable, and long-term survival is rare. The use of PCI has recently been reported to further improve overall survival in ES-SCLC. Several newer cytotoxic agents, such as amrubicin, have promising activity in early clinical trials. Although many potential molecular targets have been identified in preclinical studies of SCLC, molecularly targeted therapy has yet to demonstrate any substantial activity in clinical trials. Nonetheless, future advances in this disease will undoubtedly depend on improvements in our understanding of the molecular mechanisms that drive the proliferation and survival of SCLC cells. © Thieme Medical Publishers.