Description

Octreotide acetate is a somatostatin analog that has similar effects in the body as those of the naturally occurring hormone. It inhibits the secretion of growth hormone, glucagon, insulin, gastrin, vasoactive intestinal peptide, secretin, motilin and pancreatic polypeptide. In addition, it suppresses the response of luteinizing hormone (LH) in response to gonadotropin releasing hormone (GnRH) and decreases splenic blood flow. Octreotide acetate is available as an immediate release formulation, Sandostatin^®, and a long acting formulation, Sandostatin LAR^® Depot. Octreotide acetate suppresses secretion of growth hormone and secondarily suppresses insulin-like growth factor-1 (IGF-1, somatomedin C) and is a treatment option for those with acromegaly. Studies have shown that after immediate release octreotide acetate administration, growth hormone and IGF-1 levels are normalized in 50 – 60 percent of patients. Octreotide acetate also suppresses the release of the peptides and amines secreted from carcinoid syndrome and vasoactive intestinal peptide tumors (VIPomas), which subsequently reduces the severe diarrhea and flushing associated with this disease.

Policy
Octreotide acetate long acting injection (Sandostatin LAR^® Depot) meets the definition of MEDICALLY NECESSARY when administered for the following indications and ALL of the associated criteria are met:

1. Acromegaly: When used as long-term therapy, the dose does not exceed 40 mg per 28-day treatment cycle, and meets all the following:
   1. Member has had an inadequate response to surgery and/or radiotherapy, or member is not a candidate for surgery and/or radiotherapy.
   2. Trial and failure or intolerance to a dopamine agonist (e.g., bromocriptine or cabergoline) at maximally tolerated doses (for those with initial IGF1 levels of ≤ 1.5 x ULN).
   3. For Sandostatin LAR, patient has had a trial of short-acting octreotide and responded to and tolerated therapy.
2. Carcinoid Tumors: Long-term treatment of the severe diarrhea and flushing episodes associated with unresectable or metastatic carcinoid tumors when dosage does not exceed 30 mg per 28 day treatment cycle.
3. Vasoactive Intestinal Peptide Tumors (VIPomas): Long-term treatment of the profuse watery diarrhea associated with VIP-secreting tumors when dosage does not exceed 30 mg per 28 day treatment cycle.

Lanreotide long acting injection (Somatuline Depot) meets the definition of MEDICALLY NECESSARY when administered for the following indications and ALL of the associated criteria are met:

1. Acromegaly: Long-term treatment of acromegaly in patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option.
2. Carcinoid syndrome: Treatment of carcinoid syndrome in adults (to reduce the frequency of short acting somatostatin analog rescue therapy).
3. Gastroenteropancreatic neuroendocrine tumors: Treatment (to improve progression-free survival) of unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults.
    

Compendial Uses

1. Neuroendocrine tumors (NETs):
   • Adrenal gland tumors
   • Tumors of the gastrointestinal tract (carcinoid tumors)
   • Tumor of the thymus (carcinoid tumors)
   • Tumor of the lung (carcinoid tumors)
   • Tumors of pancreas
   • Poorly differentiated (high-grade)/large or small cell tumors (excluding lung)
2. Meningiomas
3. Thymomas and thymic carcinomas
4. Congenital hyperinsulinism (CHI)/persistent hyperinsulinemic hypoglycemia of infancy (PHHI) (octreotide and Sandostatin only)
5. Hepatorenal syndrome

All other indications are investigational/unproven therefore considered NOT MEDICALLY NECESSARY and are not a covered benefit.

Rationale:
Currently, somatostatin analogs are the most effective medical therapy available for the treatment of acromegaly. Octreotide is the first somatostatin analog used for this indication. Initially, it was administered subcutaneously at doses of 100 to 500 ug thrice daily. The advent of new depot formulations, such as LAR octreotide, slow-release lanreotide and lanreotide autogel (Somatuline Autogel), improved patients' compliance with long-term therapy, overcoming the inconvenience of multiple daily doses. It has been reported that somatostatin analogs induce biochemical control and tumor shrinkage in about 50 to 70 percent and 30 to 60 percent of patients with acromegaly, respectively.

Octreotide is approved by the FDA for use in the management of patients with acromegaly, carcinoid tumors and VIP-secreting tumors. A consensus development panel on diarrhea management (Harris et al., 1995) established guidelines for octreotide dose titration in patients with secretory diarrhea.

References:

1. Haruma K, Wiste JA, Camilleri M. Effect of octreotide on gastrointestinal pressure profiles in health and in functional and organic gastrointestinal disorders. Gut. 1994;35(8):1064-1069.
2. Harris AG, O'Dorisio TM, Woltering EA, et al. Consensus statement: Octreotide dose titration in secretory diarrhea. Diarrhea Management Consensus Development Panel. Dig Dis Sci. 1995;40(7):1464-1473.
3. Dogliotti L, Tampellini M, Stivanello M, et al. The clinical management of neuroendocrine tumors with long-acting repeatable (LAR) octreotide: Comparison with standard subcutaneous octreotide therapy. Ann Oncol. 2001;12 Suppl 2:S105-S109.
4. Moore D, Meads C, Roberts L, Song F. The effectiveness and cost-effectiveness of somatostatin analogues in the treatment of acromegaly. DPHE Report No. 37. Birmingham, UK: West Midlands Health Technology Assessment Collaboration (WMHTAC), Department of Public Health and Epidemiology (DPHE), University of Birmingham; 2002.
5. American Gastroenterological Association. American Gastroenterological Association medical position statement: Guidelines for the evaluation and management of chronic diarrhea. Gastroenterology. 1999;116(6):1461-1463.
6. Freda PU. How effective are current therapies for acromegaly? Growth Horm IGF Res. 2003;13 Suppl A:S144-S151.
7. Ramage JK, Davies AHG, Ardill J, et al.; UKNETwork for Neuroendocrine Tumours. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut. 2005;54(Suppl IV):iv1 - iv16.
8. National Comprehensive Cancer Network (NCCN). Neuroendocrine tumors. Clinical Practice Guidelines in Oncology. Version 1.2005. Jenkintown, PA: NCCN; 2005.
9. U.S. Food and Drug Administration (FDA). FDA approves new drug to treat rare disease, acromegaly. FDA News. Rockville, MD: FDA; August 30, 2007. Available at: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01692.html. Accessed June 1, 2009.
10. Samonakis DN, Notas G, Christodoulakis N, Kouroumalis EA. Mechanisms of action and resistance of somatostatin analogues for the treatment of hepatocellular carcinoma: A message not well taken. Dig Dis Sci. 2008;53(9):2359-2365.
11. Murphy G, Perras C, Desjardins B, et al. Octreotide for endocrine, oncologic, and gastrointestinal disorders: Systematic review and budget impact analysis. Technology Report. HTA Issue 117. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health (CADTH); July 2008.
12. O'Toole D, Ducreux M, Bommelaer G, et al. Treatment of carcinoid syndrome: A prospective crossover evaluation of lanreotide versus octreotide in terms of efficacy, patient acceptability, and tolerance. Cancer. 2000;88(4):770-776. 
13. Ruszniewski P, Ish-Shalom S, Wymenga M, et al. Rapid and sustained relief from the symptoms of carcinoid syndrome: Results from an open 6-month study of the 28-day prolonged-release formulation of lanreotide. Neuroendocrinology. 2004;80(4):244-251.
14. Khan MS, El-Khouly F, Davies P, et al. Long-term results of treatment of malignant carcinoid syndrome with prolonged release Lanreotide (Somatuline Autogel). Aliment Pharmacol Ther. 2011;34(2):235-242. 
15. Goldfinger SE, Strosberg JR. Treatment of the carcinoid syndrome. Last reviewed June 2012. UpToDate Inc. Waltham, MA.
16. National Comprehensive Cancer Network (NCCN). Neuroendocrine tumors. NCCN Clinical Practice Guidelines in Oncology, v.1.2013. Fort Washington, PA: NCCN; 2013.

Coding Section 

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

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