Targeted therapies

Abstract

Neuroendocrine neoplasms (NENs) are relatively rare and constitute a heterogenous group of tumors. Despite the fact that the majority of NENs are well differentiated and have an indolent course, more than half of the patients have unresectable disease due to locally advanced tumors or metastases at the time of diagnosis. Several factors affect patient survival, including presence of distant metastases, tumor grade, tumor size, and primary tumor location. Several options for the management of metastatic disease are available, including cytoreductive surgery, liver embolization and tumour ablation, radiolabeled somatostatin analogs, and medical treatment, including somatostatin analogs, interferon, chemotherapy, and recently introduced molecular targeted therapies. Streptozotocin-based chemotherapy has been used for the treatment of pancreatic neuroendocrine tumors (NETs) for the last 3 decades with response rates of up to 40 %. However, in small intestinal and hindgut NETs, the response rates have been poor. Recently, temozolomide has been shown to produce partial responses in pancreatic and other foregut NETs as a single agent or in combination with other drugs. All the studies have been retrospective and included a small number of patients with different tumor types. Ki-67 is an independent prognostic marker of survival and has been used to guide therapeutic decisions, but it cannot predict sensitivity to chemotherapy. With the introduction of molecular targeted treatment (everolimus, sunitinib), there is an urgent need to find predictive markers for sensitivity to the different therapies and also to establish evidence-based treatment algorithms for the different types of NETs with recommendations for simultaneous or sequential use of available options.