New treatment options for patients with advanced neuroendocrine tumors.

Well- to moderately differentiated neuroendocrine tumors (NET) are a heterogeneous group of malignancies for which a range of therapeutic options have been employed. For patients with localized NET, surgical resection remains the mainstay of treatment. Surgical resection of hepatic metastases or hepatic artery embolization may also be beneficial in patients with hepatic-predominant metastatic disease. Symptoms of hormonal excess, such as carcinoid syndrome and syndromes associated with functional pancreatic NET, can be effectively treated with somatostatin analogs. Systemic treatment options for patients with advanced NET have been limited. Treatment with the somatostatin analog octreotide has been shown to improve progression-free survival in patients with advanced midgut carcinoid tumors, and the potential antiproliferative effect of somatostatin analogs in patients with other NET subtypes is currently under investigation. Patients with advanced pancreatic NET may also respond to treatment with streptozocin or temozolomide-based therapy. In patients with advanced pancreatic NET, randomized, placebo-controlled studies have recently demonstrated that treatment with the tyrosine kinase inhibitor sunitinib or with the mTOR inhibitor everolimus is associated with improved progression-free survival. Based on these studies, sunitinib or everolimus should now be considered as therapeutic options in patients with advanced pancreatic NET. Initial phase II studies have also suggested activity associated with VEGF pathway and mTOR inhibitors in patients with advanced carcinoid tumors. Future studies will likely further define the role of these agents in the advanced carcinoid patient population.