Antiproliferative effect of somatostatin analogs in gastroenteropancreatic neuroendocrine tumors

Abstract

Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuroendocrine tumors (NETs). In recent years, accumulating data has supported their role as antiproliferative agents, capable of stabilizing tumor growth in patients with metastatic neuroendocrine malignancies, including carcinoid and pancreatic endocrine tumors. A phase III, randomized, placebo-controlled trial has now demonstrated that octreotide long-acting repeatable (LAR) 30 mg can significantly prolong time to tumor progression among patients with metastatic midgut NETs regardless of functional status, chromogranin A level or age. In addition to significantly lengthening time to tumor progression in the overall study population, subset analysis suggests that patients with low tumor burden are most likely to experience disease stabilization with octreotide LAR 30 mg, supporting the early use of octreotide LAR in patients with metastatic disease. Further research efforts are underway to evaluate the use of somatostatin analogs as antiproliferative agents in other types of gastroenteropancreatic-NETs. Ongoing studies are also evaluating novel somatostatin analogs and somatostatin analogs in combination with other anti-tumor therapies.

Figure 1

Chemical structure of the synthetic somatostatin analogs octreotide and lanreotide (adapted from[11]).

Figure 2

Somatostatin receptor-mediated effects on neuroendocrine cells (adapted from[23]).

Figure 3

Kaplan Meier curve demonstrating time to tumor progression in patients treated with octreotide long-acting repeatable (LAR) vs placebo[69]. Log-rank test stratified by functional activity: P = 0.000072, HR = 0.34 (95% CI: 0.20-0.59).