Chemotherapy in gastroenteropancreatic (GEP) neuroendocrine carcinomas (NEC): A critical view

Neuroendocrine tumors (NET) are classified according to the Ki67 in low-intermediate grade (Ki67 < 20%) and high grade (Ki67 > 20%). The NET of the latter group are also known as neuroendocrine carcinoma (NEC), and their prognosis is dismail. While in the former group biotherapy and radionuclide therapy can be proposed, chemotherapy represents the only treatment usually proposed for NEC. Cisplatin/etoposide combination is usually chosen based on the rationale that NEC are clinically similar to small cell lung cancer. However, evidence for cisplatin/etoposide in NEC is poor and controversial, and different schedules and response rate have been published so far. These aspects, combined with the heterogeneous characteristics of NEC, prompt us to have some doubt in considering cisplatin/etoposide as the gold standard. Some evidence exists that carboplatin can be used instead of cisplatin and irinotecan instead of etoposide without reducing efficacy. Furthermore other drugs, as gemcitabine, oxaliplatin or temozolomide can be evaluated in NEC with non-neuroendocrine component or in mixed adenoneuroendocrine carcinomas. NEC are a category of NET that should be deeply studied to verify if the response to cisplatin/etoposide is homogeneous related to the different Ki67, different morphology and/or different primary site.