Anti-proliferative effect of somatostatin analogues in gastroenteropancreatic neuroendocrine tumours

Abstract

Gastroenteropancreatic neuroendocrine tumours (GEP NET) belong to a heterogeneous group of rare tumours. Most NETs of the gastrointestinal tract are non-functioning and therefore are diagnosed at an advanced stage, which impedes radical surgery. Overexpression of somatostatin receptors (SSTR) can be found in most GEP-NETs. Somatostatin analogues play a major role in therapy of hormonally active NETs. These agents also have an anti-proliferative effect, interacting directly with membrane receptors on tumour cells or by indirect inhibition of growth factors, angiogenesis, induction of apoptosis, or their effect on the immune system. The anti-proliferative effect of octreotide LAR was demonstrated in the phase III randomised study PROMID, which included 84 treatment-naive patients with disseminated well differentiated NETs of midgut or unknown origin. The anti-tumour effect of octreotide LAR was observed irrespective of tumour functional status. Additionally, a retrospective study was presented at the ASCO meeting in 2014, showing a therapeutic effect of octreotide LAR of even longer duration than in the PROMID study. Authors of the report identified also favourable predictive factors for octreotide LAR therapy. The anti-proliferative effect of lanreotide Autogel^® was demonstrated in the CLARINET study, which included 204 patients with non-functioning GEP-NETs, differentiation grade of G1 or G2, proliferation index Ki-67 up to 10%, locally inoperable, or metastasised. Results of the study showed decreased relative risk of disease progression by 53% in patients with GEP-NETs located in the pancreas, midgut, or of unknown origin.