Small cell lung cancer (SCLC) is an aggressive type of lung cancer characterized by rapid growth and early metastasis. It is chemosensitive and radiosensitive, yet decades of research investigating multimodality treatments have failed to control or cure this disease in most patients. First-line treatment of limited-stage disease consists of chemotherapy (often etoposide/cisplatin or etoposide/carboplatin) combined with thoracic radiation therapy (TRT), followed by prophylactic cranial irradiation to decrease brain metastases as a site of disease progression for those who experience complete remission or a very good partial response to multimodality treatment. In a Japanese trial, the combination of irinotecan and cisplatin had initially shown promise in treating patients with extensive-stage SCLC, but a confirmatory trial in the United States did not find a difference in overall survival with irinotecan/cisplatin versus etoposide/cisplatin. Adding a third drug to the etoposide/cisplatin combination, as well as other triplet therapies, has mostly been ineffective in improving outcomes. Variables in chemotherapy administration, including maintenance therapy, alternating non-cross-resistance regimens, and dose intensification, have not been shown to increase survival at large. In terms of radiation therapy, early administration of TRT concurrent with chemotherapy, and hyperfractionation, have been beneficial in treatment of limited-stage disease. In patients who relapse, second-line therapy options consist of reinduction of previous chemotherapy or administration of a single agent. Targeted biological therapies for SCLC are now being investigated, and although a great deal of research remains to be done, these agents and their derivatives may provide the most hope for future treatment of SCLC.
