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

被引：156

作者：

Stueven, Anna Kathrin ^{[1
,2
]}

Kayser, Antonin ^{[1
,2
]}

Wetz, Christoph ^{[1
,3
]}

Amthauer, Holger ^{[1
,3
]}

Wree, Alexander ^{[1
,2
]}

Tacke, Frank ^{[1
,2
]}

Wiedenmann, Bertram ^{[1
,2
]}

Roderburg, Christoph ^{[1
,2
]}

Jann, Henning ^{[1
,2
]}

机构：

[1] Univ Med Berlin, Charite, Campus Virchow Klinikum, D-10117 Berlin, Germany

[2] Univ Med Berlin, Charite, Campus Mitte, Dept Hepatol & Gastroenterol, D-10117 Berlin, Germany

[3] Univ Med Berlin, Charite, Campus Mitte, Dept Nucl Med, D-10117 Berlin, Germany

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 12期

关键词：

neuroendocrine tumor; carcinoid; somatostatin analogue; octreotide; lanreotide; PROMID; CLARINET; PRRT; NETTER-1; RECEPTOR RADIONUCLIDE THERAPY; CARCINOID HEART-DISEASE; GROWTH-HORMONE RELEASE; OCTREOTIDE LAR; MOLECULAR-MECHANISMS; PASIREOTIDE SOM230; CLINICAL SYMPTOMS; ENDOCRINE TUMORS; OPEN-LABEL; PHASE-I;

D O I：

10.3390/ijms20123049

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：13

共 105 条

[21] IMMUNOREACTIVE SOMATOSTATIN IS PRESENT IN DISCRETE CELLS OF ENDOCRINE PANCREAS [J].