Management of neuroendocrine tumors: current and future therapies

Neuroendocrine tumors (NETs) are a genetically diverse group of malignancies that sometimes produce peptides that cause characteristic hormonal syndromes. NETs can be clinically symptomatic (functioning) or silent (nonfunctioning); both types frequently synthesize more than one peptide, although often these are not associated with specific syndromes. Based on data from various sources, the incidence and prevalence of NETs is increasing. The primary treatment goal for patients with NETs is curative, with symptom control and the limitation of tumor progression as secondary goals. Surgery is the only possible curative approach and so represents the traditional first-line therapy. However, as most patients with NETs are diagnosed once metastases have occurred, curative surgery is generally not possible. Patients therefore require chronic postoperative medical management with the aim of relieving symptoms and, in recent years, suppressing tumor growth and spread. Somatostatin analogues, such as octreotide long-acting repeatable (LAR), can improve the symptoms of carcinoid syndrome and stabilize tumor growth in many patients. Results from the placebo-controlled, double-blind, prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors (PROMID study) demonstrate that octreotide LAR 30 mg is an effective antiproliferative treatment in patients with newly diagnosed, functionally active or inactive, well-differentiated metastatic midgut NETs. An antiproliferative effect can also be achieved with everolimus, and combination therapy with octreotide LAR has shown synergistic antiproliferative activity. Sunitinib, a tyrosine kinase inhibitor, is active in pancreatic NETs. In the future, pasireotide, the multireceptor targeted somatostatin analogue, has the potential to be an effective therapy for de novo or octreotide-refractory carcinoid syndrome and for inhibiting tumor cell proliferation. Peptide receptor radiotherapy with ⁹⁰Yttrium-DOTATOC or ¹⁷⁷Lutetium-DOTATE is also a new interesting treatment option for NETs.