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Lung cancer is leading cause of cancer death in many advanced countries and one of the challenging malignancies because of poor prognosis. Lung cancer is traditionally divided into two major categories, so called small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) because of distinctive prognostic and treatment strategies between them. On the other hand, there is a spectrum of tumors called pulmonary neuroendocrine (NE) tumors that are thought to originate from neuroendocrine cells in the pulmonary and bronchial epithelium. Until recently, pulmonary NE tumors were classified into three categories, i.e., typical carcinoid (TC), atypical carcinoid (AC), and SCLC. Large cell neuroendocrine carcinoma (LCNEC) of the lung was officially identified by Travis et al. in 1991 as a fourth category, a unique higher grade NSCLC existing between TC and SCLC (Travis et al., 1991). It is often difficult to diagnose LCNEC with small biopsy specimens because accurate diagnosis needs morphological and immunohistochemical information. Although earlier reports mainly focused on prognosis after surgical procedures, several recent studies reported on the efficacy of chemotherapy for advanced LCNEC. Because of the limited numbers of cases (in surgical series, LCNEC represents ~3% of lung cancers), large scale prospective studies have not been reported. Standard treatment for LCNEC, especially if advanced, is not established although LCNEC is included in NSCLC in the treatment algorithm in many guidelines. However, accumulating data including recent retrospective studies have suggested that there is similarity in the prognosis and treatment response between LCNEC and SCLC. In this review, we will focus on the treatment of advanced LCNEC for the better selection of chemotherapeutic regimens for the patients with this relatively rare lung cancer.

Chemotherapy for Large Cell Neuroendocrine Carcinoma of the Lung: Should It Be Treated with the Same Strategy as Small Cell Lung Carcinoma?