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Somatostatin Analogues in the Treatment of Neuroendocrine Tumors: Past, Present and Future

1
Charité, Campus Virchow Klinikum and Charité, Campus Mitte, Department of Hepatology and Gastroenterology, Universitätsmedizin Berlin, 10117 Berlin, Germany
2
Charité, Campus Virchow Klinikum and Charité, Campus Mitte, Department of Nuclear Medicine, Universitätsmedizin Berlin, 10117 Berlin, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(12), 3049; https://doi.org/10.3390/ijms20123049
Received: 3 May 2019 / Revised: 6 June 2019 / Accepted: 19 June 2019 / Published: 22 June 2019
(This article belongs to the Special Issue Somatostatin)
In recent decades, the incidence of neuroendocrine tumors (NETs) has steadily increased. Due to the slow-growing nature of these tumors and the lack of early symptoms, most cases are diagnosed at advanced stages, when curative treatment options are no longer available. Prognosis and survival of patients with NETs are determined by the location of the primary lesion, biochemical functional status, differentiation, initial staging, and response to treatment. Somatostatin analogue (SSA) therapy has been a mainstay of antisecretory therapy in functioning neuroendocrine tumors, which cause various clinical symptoms depending on hormonal hypersecretion. Beyond symptomatic management, recent research demonstrates that SSAs exert antiproliferative effects and inhibit tumor growth via the somatostatin receptor 2 (SSTR2). Both the PROMID (placebo-controlled, prospective, randomized study in patients with metastatic neuroendocrine midgut tumors) and the CLARINET (controlled study of lanreotide antiproliferative response in neuroendocrine tumors) trial showed a statistically significant prolongation of time to progression/progression-free survival (TTP/PFS) upon SSA treatment, compared to placebo. Moreover, the combination of SSA with peptide receptor radionuclide therapy (PRRT) in small intestinal NETs has proven efficacy in the phase 3 neuroendocrine tumours therapy (NETTER 1) trial. PRRT is currently being tested for enteropancreatic NETs versus everolimus in the COMPETE trial, and the potential of SSTR-antagonists in PRRT is now being evaluated in early phase I/II clinical trials. This review provides a synopsis on the pharmacological development of SSAs and their use as antisecretory drugs. Moreover, this review highlights the clinical evidence of SSAs in monotherapy, and in combination with other treatment modalities, as applied to the antiproliferative management of neuroendocrine tumors with special attention to recent high-quality phase III trials. View Full-Text
Keywords: neuroendocrine tumor; carcinoid; somatostatin analogue; octreotide; lanreotide; PROMID; CLARINET; PRRT; NETTER-1 neuroendocrine tumor; carcinoid; somatostatin analogue; octreotide; lanreotide; PROMID; CLARINET; PRRT; NETTER-1
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MDPI and ACS Style

Stueven, A.K.; Kayser, A.; Wetz, C.; Amthauer, H.; Wree, A.; Tacke, F.; Wiedenmann, B.; Roderburg, C.; Jann, H. Somatostatin Analogues in the Treatment of Neuroendocrine Tumors: Past, Present and Future. Int. J. Mol. Sci. 2019, 20, 3049.

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