Medical Therapy of Pulmonary Neuroendocrine Neoplasms: Targeted, Symptomatic and Chemotherapy.

Whenever feasible, surgery represents the treatment of choice for pulmonary neuroendocrine neoplasms (NENs). In patients with hypersecreting tumors, wide metastatic spread or those not candidates for a surgical treatment, medical therapies may assure a control of the secretory pattern and slow the rate of tumor growth. No specific trials have been designed so far for pulmonary NENs and the first randomized trial entirely dedicated to thoracic NENs (the LUNA trial) is ongoing. International scientific society guidelines (ESMO and NANETS) and recommendations (ENETS) are therefore necessarily based on expert experience, on the subgroup analysis of large multicenter trials not focused on pulmonary NENs, and on the analysis of small retrospective series. Somatostatin analogs represent the therapy of choice in the presence of associated carcinoid syndrome and ectopic acromegaly and a reasonable first-line in slow-progressing tumors. Due to the low rate of proliferation, platinum-based chemotherapy is generally reserved to rapidly progressing tumors. Temozolomide alone or in association has shown activity in small retrospective series or monocentric trials - larger multicenter trials will better define its efficacy. Everolimus alone or in combination with somatostatin analogs has shown activity in the subgroup analysis of a large multicenter trial (RADIANT II). Many other drugs have shown activity in the preclinical models but, at the moment, no prospective and randomized data are available.