Chemotherapy in gastroenterologic neuroendocrine tumors

Gastrointestinal neuroendocrine tumors (carcinoids tumors and endocrine islet cell tumors) are a family of rare malignancies with many typical characteristics by a biologic, epidemiologic and clinical point of view. In this category of neoplasia an integrated clinical and therapeutic approach is mandatory, whereas for too many years these tumors were investigated and treated in an empirical way without considering an integrated approach. The singular features of this class of malignancies, with different and complex symptomatology, with enigmatic clinical presentation and outcome and with conflicting therapeutic options, oblige the clinicians to give different treatment to the patients. Chemotherapy has a marginal role in gastrointestinal neuroendocrine tumors mostly because it is used in patients with advanced disease not suitable for other therapeutic approach (surgery, thermoablation, chemoembolization, biotherapy). Unfortunately in the past it was not possible to establish the efficacy of chemotherapy in these malignancies because most of the studies pooled without distinction carcinoids, pancreatic tumors and hepatic metastases from unknown primary. The most extensively studied drugs have been streptozotocin, doxorubicin, mitoxantrone, dacarbazine, used alone or in combination; the gold standard today is considered the association of streptozotocin with doxorubicin or 5-fluorouracil, but there is strong evidence that the disappointing results in the treatment of these rare malignancies could be improved in a multidisciplinary fashion; in this field the combination of new drugs with aggressive surgery, radionuclide therapy, biotherapy and local therapeutic approach will give new opportunities to better control the symptoms and the clinical course of gastrointestinal neuroendocrine tumors.