Update on the role of somatostatin analogs for the treatment of patients with gastroenteropancreatic neuroendocrine tumors

Abstract

Somatostatin analogs (SA) are the standard of care for controlling symptoms of patients with functional gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). SA control symptoms in more than 70% of patients with carcinoid syndrome. Similar results are obtained in patients with functional, hormone-secreting, pancreatic NETs. The use of SA as antiproliferative agents has been established only recently. Retrospective studies have shown stabilization of tumor growth in >50% of patients with progressive disease. The results of a recent randomized phase III trial (PROMID) demonstrated that the median time to progression in patients with midgut carcinoid tumors treated with octreotide LAR (Long-Acting-Repeatable, Novartis, Basel, Switzerland) was more than twice as long compared to that of patients treated with placebo. The results of a phase III study of lanreotide versus placebo in nonfunctional NETs are not yet available. More studies are needed to determine whether combining SA with novel targeted treatments will result in enhanced antiproliferative activity compared to treatment with a SA alone. Studies are ongoing using pan-receptor agonists (eg, pasireotide) and chimeric dimers, which possess features of somatostatin and dopamine agonists (dopastatins) and are thought to enhance symptom control by binding multiple receptors (somatostatin and dopamine receptors). Somatostatin receptor antagonists are also currently being developed for clinical use. Peptide receptor radionuclide therapy (PRRT), consisting of yttrium-90 and lutetium-177 isotopes conjugated with SA appear to be efficacious in advanced NETs. Randomized studies are needed to definitively establish the safety and efficacy of this strategy compared to other available treatments, and to determine which radiolabeled isotopes or combinations are most effective.