Antiproliferative Effect of Somatostatin Analogs – Data Analyses and Clinical Applications in the Context of the CLARINET Study
Authors:
B. Bencsiková
Authors place of work:
Klinika komplexní onkologické péče, Masarykův onkologický ústav, Brno RECAMO, Masarykův onkologický ústav, Brno
Published in the journal:
Klin Onkol 2016; 29(4): 253-258
Category:
Review
doi:
https://doi.org/10.14735/amko2016253
Summary
Background:
Somatostatin analogs (SSAs) are antisecretory agents that have been used to control hormonal syndromes associated with neuroendocrine tumors for more than 20 years. Recent phase III randomized, placebo controlled trials demonstrated their antiproliferative effects. The PROMID study showed that octreotide LAR (long-acting repeatable) treatment had anti-tumor effects. CLARINET, an international multicenter controlled study, provides new evidence that lanreotide has antiproliferative effects. Depot lanreotide significantly prolonged progression-free survival among patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Because GEP-NETs are biologically diverse in terms of primary tumor site and functional status, preventing progression can be difficult.
Aim:
This review summarizes data supporting the role of SSAs, in particular lanreotide, as antiproliferative agents for the treatment of patients with GEP-NETs.
Conclusion:
The CLARINET study is the most powerful (in sence of data, results, clinical aplication) randomized study of the antiproliferative effects of SSA in GEP-NET patients. The median lanreotide-associated progression-free survival in the CLARINET core study or in open-label extension study was 32.8 vs. 18 months for placebo. Thus, early treatment with lanreotide is expected to prolong progression-free survival. Lanreotide is now recommended for the treatment of patients with well-differentiated metastatic grade 1 and grade 2 GEP-NETs (i.e., those with a Ki-67 proliferative index < 10%) located in the pancreas, small intestine, or in cases where the location of the primary tumor is unknown, regardless of the degree of liver involvement.
Key words:
somatostatin – neuroendocrine tumors – angiogenesis – apoptosis – antiproliferative effect
This work was supported by MEYS-NPS I-LO1413.
The author declares she has no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Submitted:
2. 12. 2015
Accepted:
20. 3. 2016
Zdroje
1. Tomášek J et al. Onkologie minimum pro praxi. 1. vyd. Praha: Axonite Edice Asclepius 2015: 237.
2. Boznan F, Carneiro FT, Hrubon RH et al. World Health Organization Classification of tumours, pathology and genetics of tumours of the digestive system. Lyon: IARC Press 2010.
3. Brazeau P, Gullemin R. Editorial: Somatostatin: nextcomer from the hypothalamus. N Engl J Med 1974; 290(17): 963– 964.
4. Ganong WF. Přehled lékařské fyziologie. 20. vyd. Praha: Galén 2005: 890.
5. Ehrmann J, Hůlek P et al. Hepatologie. 2. vyd. Praha: Grada 2014: 186.
6. Patel YC, Srikant CB. Somatostatin receptors. Trends Endocrinol Metab 1997; 8(10): 398– 405.
7. Papotti M, Bongiovanni M, Volante M et al. Expression of somatostatin receptor types 1–5 in 81 cases of gastrointestinal and pancreatic endocrine tumors. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis. Virchows Arch 2002; 440(5): 461– 475.
8. Kaemmerer D, Specht E, Sänger J et al. Somatostatin receptors in bronchopulmonary neuroendocrine neoplasms: new diagnostic, prognostic, and therapeutic markers. J Clin Endocrinol Metab 2015; 100(3): 831– 840. doi: 10.1210/ jc.2014-2699.
9. Castaño JP, Sundin A, Maecke HR et al. Gatrointestinal neuroendocrine tumors (NETs): new diagnostic and therapeutic challenges. Cancer Metastasis Rev 2014; 33(1): 353– 359. doi: 10.1007/ s10555-013-9465-1.
10. Modlin IM, Pavel M, Kidd M et al. Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours. Aliment Pharmacl Ther 2010; 31(2): 169– 188. doi: 10.1111/ j.1365-2036.2009.04174.x.
11. Oberg K. Established clinical use of octreotide and lanreotide in oncology. Chemotherapy 2001; 47 (Suppl 2):40– 53.
12. Colao A, Petersenn S, Newell-Price J et al. Pasireotide B2305 Study Group. A 12-month phase 3 study of pasireotide in Cushing‘s disease. N Engl J Med 2012; 366(10): 914– 924. doi: 10.1056/ NEJMoa1105743.
13. Caron PJ, Bevan JS, Petersenn S et al. Tumor shrinkage with lanreotide autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial. J Clin Endocrinol Metab 2014; 99(4): 1282– 1290. doi: 10.1210/ jc.2013-3318.
14. Weckbecker G, Lewis I, Albert R et al. Opportunities in somatostatin research: biological, chemical and therapeutical aspects. Nat Rev Drug Discov 2003; 2(12): 999– 1017.
15. Florio T. Somatostatin receptor signalling: phosphotyrosine phosphatases. Mol Cell Endocrinol 2008; 286(1– 2): 40– 48.
16. Lattuada D, Casnici C, Venuto A. The apoptotic effect of somatostatin analouges SMS 201–995 on human lymphocytes. J Neuroimmunol 2002; 133(1– 2): 211– 216.
17. Eriksson B, Oberg K. Summing up 15 years of somatostatin analog therapy in neuroendocrine tumors: future outlook. Ann Oncol 1999; 10 (Suppl 2): S31– S38.
18. Kumar M, Liu ZR, Thapa L et al. Angiogenic effect of somatostatin receptor subtype 2 on pancreatic cancer cell line: inhibition of vascular endothelial growth factor and matrix metalloproteinase-2 expression in vitro. World J Gastroenterol 2004; 10(3): 393– 399.
19. Woltering EA, Watson JC, Perin-Lea RC et al. Somatostatin analogs: angiogenesis inhibitors with novel mechanism of action. Invest New Drugs 1997; 15: 77– 86.
20. Adams RL, Adams IP, Lindow SW et al. Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endothelium. Br J Cancer 2005; 92(8): 1493– 1498.
21. Arena S, Pattarozzi A, Corsaro A et al. Somatostatin receptor subtype-dependent regulation of nitric oxide release: involvement of different intracellular pathways. Mol Endocrinol 2005; 19(1): 255– 267.
22. Kumar M, Liu ZR, Thapa L et al. Anti-angiogenic effects of somatostatin receptor subtype 2 on human pancreatic cancer xenografts. Carcinogenesis 2004; 25(11): 2075– 2081.
23. Dimitroulopoulos D, Xinopoulos D, Tsamakidis K. Long acting octreotide in the treatment of advanced hepatocellular carcinoma. J Cancer Res Clin Oncol 2006; 132(11): 699– 708.
24. Lichtenauer-Kaligis EG, Dalm VA, Oomen SP et al. Differential expression of somatostatin receptor subtypes in human peripheral blood mononuclear cell subsets. Eur J Endocrinol 2004; 150(4): 565– 577.
25. Susini C, Buscali L. Rationale for the use of somatostatin analogs as antitumor agents. Ann Oncol 2006; 17(12): 1733– 1742.
26. Reubi JC. A somatostatin analogue inhibits chondrosarkoma and insulinoma tumor growth. Acta Endocrinol 1985; 109(1): 108– 114.
27. Romeo S, Milione M, Gatti A. Complete clinical remission and disappearance of liver metastases after treatment with somatostatin analogues in a 40-year-old woman with a malignant insulinoma positive for somatostatin receptors type 2. Horm Res 2006; 65(3): 120– 125.
28. Eriksson B, Renstrup J, Imam H et al. High-dose treatment with lanreotide of patients with advanced neuroendocrine gastrointestinal tumors: clinical and biological effects. Ann Oncol 1997; 8(10): 1041– 1044.
29. Faiss S, Rath U, Mansmann U. Ultra-high-dose lanreotide treatment in patients with metastatic neuroendocrine gastroenteropancreatic tumors. Digestion 1999; 60(5): 469– 476.
30. Kvols LK, Woltering EA. Role of somatostatin analogs in the clinical management of non-neuroendocrine solid tumors. Anticancer Drugs 2006; 17(6): 601– 608.
31. Panzuto F, Di Fonzo M, Iannicelli E. Long-term clinical outcome of somatostatin analogues for treatment of progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinoma. Ann Oncol 2006; 17(3): 461– 466.
32. Faiss S, Scherubl H, Riecken EO. Drug therapy in metastatic neuroendocrine tumors of the gastroenteropancreatic system. Recent Results Cancer Res 1996; 142: 193– 207.
33. Welin SV, Janson ET, Sundin A. High-dose treatment with a long-acting somatostatin analogue in patients with advanced midgut carcinoid tumours. Eur J Endocrinol 2004; 151(1): 107– 112.
34. Rinke A, Müller HH, Schade-Brittinger C et al. Placebo-controlled, double-blind, prospective, randomised study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 2009; 27(28): 4656– 4663. doi: 10.1200/ JCO.2009.22.8510.
35. Caplin ME, Pavel M, Ćwikła JB et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 2014; 371(3): 224– 233. doi: 10.1056/ NEJMoa1316158.
36. Sedláčková E. Studie CLARINET a její následná opel-label fáze. Remedia 2014; 24: 495– 498.
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Paediatric clinical oncology Surgery Clinical oncologyČlánok vyšiel v časopise
Clinical Oncology
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