Medical Therapy of Gastrointestinal Neuroendocrine Tumors

Intestinal neuroendocrine tumors (NETs) constitute a heterogeneous group with duodenal, small intestinal, colonic and rectal NETs. They constitute more than half of all NETs, with the highest frequencies in the rectum, small intestine, and colon. The tumor biology varies with the location of the primary tumor as well as with the grade and staging of the tumor. Small intestinal NETs usually present low proliferation and are treated in the first line with somatostatin analogs according to current guidelines. If progression occurs, one can add interferon alpha or change the treatment to everolimus. Peptide receptor radionuclide therapy (PRRT) with Lutetium¹⁷⁷-DOTATATE can be an option in the future after registration of the compound. Rectal tumors are usually small when they metastasize; they can be treated with somatostatin analogs but more so with PRRT, while another option is of course everolimus. Colonic NETs are more aggressive than the rest of intestinal NETs and will be treated with everolimus, sometimes in combination with somatostatin analogs based on positive scintigraphy. Another option is a cytotoxic agent such as streptozotocin plus 5-fluorouracil (5-FU) or temozolomide plus capecitabine. The most aggressive tumors, i.e. neuroendocrine carcinoma G3, are treated with a platin-based therapy plus etoposide; if they present with a lower proliferation, i.e. <50%, temozolomide plus capecitabine plus bevacizumab can also be attempted. Duodenal NETs are mostly treated similar to pancreatic NETs, either with cytotoxic agents, streptozotocin plus 5-FU, or temozolomide plus capecitabine, or with targeted agents such as everolimus.