Somatuline Depot (lanreotide) received approval in September 2017 for the treatment of carcinoid syndrome (CS). The safety and efficacy of the medication was studied in a 16 week, randomized, double blind, phase-3 trial. The trial evaluated patients for the control of carcinoid syndrome in patients with neuroendocrine tumors (NETS). Patients were randomized to receive either lanreotide 120 mg or placebo every 4 weeks, with acces to short acting octeotride as a rescue medication. Inclusion criteria included that patients be 18 years of age, a history of confirmed carcinoid tumor or carcinoid tumor of unknown location with liver metastases, a history of carcinoid syndrome, confirmation of positive somatostatin receptor status, somatostatin naïve, and absence of tumor progression. Exclusion criteria included history of treatment refractory CS, hepatic artery emolization, short bowel syndrome, uncontrolled diabetes or hypertension, severe renal and/or hepatic impairment, cardiac disease New York Heart Association classification > 1, 115 patients were enrolled. The primary endpoint, reduction in octeotride use, was lower in the lanreotide group (33.7%) versus the placebo group (48.5%), with a difference of 14.8%. The most frequent adverse effects (AEs) were gastrointestinal, including nausea (8.6%), vomiting (6.9%), and abdominal pain (8.6%. AE led to discontinuation in two patients. There were no new adverse events found compared to previous clinical trials for lanreotide.

Signifor LAR (pasireotide) is a somatostatin analog that is approved in 2014 for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option. Its efficacy and safety has been demonstrated through multicenter, randomized, active-controlled trials in both the treatment naïve and the treatment experienced populations. In the treatment naïve population, the proportion of patients achieving GH control at 12 months was 31.3% and 19.2% for Signifor LAR and active comparator, respectively. In the treatment experience population where GH was inadequately controlled via other somatostatin analogs, Biochemical control was achieved by Month 3 in 15.4% and 18.5% of subjects in the Signifor LAR 40 mg and 60 mg arms, respectively.

Policy:

(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)

The requirements of the Horizon BCBSNJ Sandostatin LAR depot (Octreotide) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).

I. Please refer to a separate policy on Site of Administration for Infusion and Injectable Prescription Medications (Policy #142) under the Drug Section for Sandostatin LAR (ocreotide acetate) and Somatuline (lanreotide).

II. Sandostatin (octreotide acetate) therapy is medically necessary for the following FDA-approved adult indications:

A. Treatment of acromegaly in patients who have had inadequate response to OR cannot be treated with surgical resection, pituitary irradiation and bromocriptine mesylate, defined by ONE of the following documented parameters:
i. Growth hormone level > 5 ng/mL, or
ii. IGF-1 level > 1.9 U/mL for males or > 2.2. U/mL for females,
[INFORMATIONAL NOTE: The efficacy of octreotide for the treatment of acromegaly was studied in three trials with acromegalic patients. In two of the clinical trials, a total of 101 patients were entered who had, in most cases, achieved a GH level <5 ng/mL on octreotide injection given in doses of 100 mcg or 200 mcg three times daily. Most patients were switched to 20 mg or 30 mg doses of octreotide LAR depot given once every 4 weeks for up to 27 to 28 injections. A few patients received doses of 10 mg and a few required doses of 40 mg. Growth hormone and IGF-1 levels were at least as well controlled with Sandostatin LAR Depot as they had been on Sandostatin Injection and this level of control remained for the entire duration of the trials. The primary endpoint, which was the reduction in mean serum growth hormone, was statistically significant compared to placebo. After 6 months, 53% of patients showed a reduction of GH to less than 5 mcg/L, while IGF-1 levels were normal in 68% of patients. Response to sandostatin was seen within 2 hours of injection, as mean serum GH reduced to 30% of pretreatment concentration. 10% and 13% of patients in treatment and placebo groups developed transient diarrhea, respectively, while other commonly seen adverse events included biliary sludge and cholelithiasis. The higher dose , 750 mcg daily, resulted in increased frequency of tumor shrinkage, but added no clinical benefit.

A third trial was a 12-month study that enrolled 151 patients who had a GH level <10 ng/mL after treatment with octreotide injection (most had levels <5 ng/mL). The starting dose of Sandostatin LAR Depot was 20 mg every 4 weeks for 3 doses. Thereafter, patients received 10 mg, 20 mg or 30 mg every 4 weeks, depending upon the degree of GH suppression. Growth hormone and IGF-1 were at least as well controlled on octreotide LAR depot as they had been on octreotide injection

The safety and efficacy of octreotide LAR was also assessed in an open label, prospective study that enrolled 67 patients with acromegaly, many of whom had macroadenomas. Patients received octreotide LAR therapy which was individually tailored. At 48 months, safe GH levels and normal IGF-1 levels were obtained by 68.7% and 70.1% of patients, respectively. The tumor shrank in 82.1% of patients, while in three patients, the tumor was shown to completely disappear. Higher baseline GH values and greater GH/IGH-1 changes on treatment corresponded with greater tumor shrinkage.]
B. Symptomatic treatment of patients with metastatic carcinoid tumors to suppress or inhibit severe diarrhea and flushing episodes

[INFORMATIONAL NOTE: Open-label subcutaneous octreotide every 8 hours was compared to octreotide LAR 10, 20, and 30 mg every 4 weeks in the treatment of diarrhea and flushing associated with carcinoid syndrome. Complete or partial treatment success was comparable in each of the four arms of the study (SC: 58.3%, 10 mg, 66.7%, 20 mg: 71.4%, 30 mg: 61.9%, p>0.72). Control of stool frequency was similar in all treatment groups, while flushing episode were best controlled in 20 mg LAR and SC groups. Once sandostatin steady-state concentrations are achieved, sandostatin LAR control the symptoms of carcinoid tumors at least as well as SC sandostatin.]

C. Treatment of profuse watery diarrhea associated with vasoactive intestinal peptide-secreting tumors

A. Long-term maintenance therapy in acromegalic patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option, defined by ONE of the following documented parameters:
i. Growth hormone level > 5 ng/mL, or
ii. IGF-1 level > 1.9 U/mL for males or > 2.2. U/mL for females

B. Long-term treatment of the severe diarrhea and flushing episodes associated with metastatic carcinoid tumors.

C. Long-term treatment of the profuse watery diarrhea associated with VIP-secreting tumors.

A. Treatment of adult patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative
B. Treatment of adult patients with acromegaly who have had an inadequate response to surgery and/or for home surgery is not an option

A. Long-term treatment of acromegalic patients who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy, defined by ONE of the following documented parameters:
i. Growth hormone level > 5 ng/mL, or
ii. IGF-1 level > 1.9 U/mL for males or > 2.2. U/mL for females,
B. Treatment of patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival
C. Treatment of adults with carcinoid syndrome to reduce the frequency of short acting somatostatin analogue rescue therapy

A. Octreotide subcutaneous injection: initiate therapy at 100-600 mcg/day SC divided 2-4 times daily; may titrate to 1500 mcg/day based on response.
B. Octreotide LAR depot: 20 mg IM every 4 weeks for 3 months; titrate up or down to 10-30 mg IM every 4 weeks as per response; do not exceed 40 mg IM every 4 weeks.
C. Pasireotide intramuscular injectable suspension:
1) Acromegaly: initial therapy at 40mg IM once every 4 weeks; adjust dose based on biochemical response and tolerability
2) Cushing’s disease: initial therapy at 10mg IM once every 4 weeks; adjust dose based on biochemical response and tolerability

[INFORMATIONAL NOTE: The recommended initial dose for patients with moderately impaired hepatic function (Child-Pugh B) is 20 mg every 4 weeks and the maximum recommended dose is 40 mg every 4 weeks. Avoid use in patients with severe hepatic impairment (Child-Pugh C)

Sandostatin LAR, Signifor LAR, and Somatuline carry a risk of cholelithiasis and complications that require periodic monitoring. Discontinue if complications of cholethiasis are suspected]

D. Lanreotide injection for acromegaly: initial therapy at 90 mg every 4 weeks for 3 months. Adjust thereafter based on GH and/or IGF-1 levels. Dose range is 60mg to 120mg every 4 weeks.

[INFORMATIONAL NOTE: Moderate and Severe Renal and Hepatic Impairment: Initial dose is 60 mg every 4 weeks for 3 months. Adjust thereafter based on GH and/or IGF-1 levels. ]

E. Lanreotide injection for GEP-NET and carcinoid syndrome: 120mg every 4 weeks

A. Cancer treatment:
a. Tumor response with stabilization of disease or decrease in size of tumor or tumor spread; AND
b. Absence of unacceptable toxicity from the drug (e.g.: gall bladder abnormalities, conduction abnormalities, or complications of cholelithiasis)
B. Non-cancer indications (indications (including control of symptoms secondary to tumor):
a. Patient continues to meet initial review criteria; AND
b. Disease response with reduction in symptoms (diarrhea, flushing, etc.) and/or stabilization of glucose levels; AND
c. Absence of unacceptable toxicity from the drug (e.g.: gall bladder abnormalities, conduction abnormalities, or complications of cholelithiasis)
d. reduction in growth hormone and/or IGF-1 from baseline (Acromegaly ONLY)

Sandostatin LAR Depot (octreotide LAR depot):
A. Meningiomas (CNS Cancers)
a. Treatment for surgically inaccessible recurrent or progressive meningiomas when further radiation is not possible, if octreotide scan is positive
B. Neuroendocrine tumor
a. Pancreas:
i. Management of symptoms related to hormone hypersecretion of locoregional disease
• consider for gastrinoma (usually duodenal or head of pancreas)
• for glucagonoma (usually tail)
• for VIPoma
ii. Consider for tumor control in patients* with locoregional advanced disease and/or distant metastatic disease; if disease progression, treatment with octreotide LAR should be continued in patients with functional tumors in combination with any of the systemic therapy options
• for asymptomatic, low tumor burden and stable disease
• for symptomatic, clinically significant tumor burden, or clinically significant progression (if disease progression and not already receiving)
*For patients with insulinoma, octreotide should be used only if somatostatin scintigraphy is positive
b. GI Tract, Lung, and Thymus:
i. Primary treatment of unresectable primary gastrinoma; OR
ii. Management of distant metastatic bronchopulmonary/thymic disease if somatostatin receptor positive and/or
• hormonal symptoms if asymptomatic, low tumor burden and low grade (typical) histology
• chronic cough/dyspnea if multiple lung nodules or tumorlets and evidence of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)
iii. Management of distant metastatic bronchopulmonary/thymic disease* if somatostatin receptor positive and/or hormonal symptoms if clinically significant tumor burden and low grade (typical) histology, evidence of progression, or intermediate grade (atypical histology)
• as primary therapy
• consider as subsequent therapy if progression on first-line therapy
iv. Management of locoregional unresectable bronchopulmonary/thymic disease* if somatostatin receptor positive and/or hormonal symptoms
• as primary therapy in patients with low grade (typical) histology
• consider as subsequent therapy if progression on first-line therapy
v. Management of locoregional advanced disease of the gastrointestinal tract and/or distant metastases*
• if asymptomatic and a low tumor burden
• with a clinically significant tumor burden
• for disease progression if not already receiving
vi. Treatment of carcinoid syndrome
• as a single agent
• in combination with telotristat for persistent diarrhea due to poorly controlled carcinoid syndrome
• in combination with other systemic therapy options for persistent symptoms such as flushing or diarrhea, or for progressive disease
*if disease progression, treatment with octreotide LAR should be continued in patients with functional tumors and may be used in combination with any of the systemic therapy options.
C. Thymic carcinoma/thymoma.
a. Second-line therapy with or without prednisone
• unresectable disease following first-line chemotherapy for potentially resectable locally advanced disease, solitary metastasis, or ipsilateral pleural metastasis
• extrathoracic metastatic disease

Sandostatin (octreotide subcutaneous injection):
A. Central Nervous System Cancers – Meningiomas
a. Treatment for surgically inaccessible recurrent or progressive meningiomas when further radiation is not possible
B. Lung Neuroendocrine Tumors
a. Consider for stage IIIb (T4 due to multiple lung nodules),-IV low, or intermediate-grade neuroendocrine carcinoma if octreotide scan positive or for symptoms of carcinoid syndrome
C. Neuroendocrine Tumors
a. Adrenal Gland Tumors
i. Used as treatment of symptoms of Cushing’s syndrome; AND
ii. Patient’s Cushing syndrome is not dependent upon adrenocorticotropic hormone (ACTH); AND
iii. Tumor is < 4 cm and has benign imaging characteristics; AND
iv. Patient has abnormal contralateral gland; AND
v. Patient has symmetric cortisol production per adrenal vein sampling; AND
vi. Patient is somatostatin receptor scintigraphy (OctreoScan) positive
b. Neuroendocrine Tumors of the Pancreas
i. Use for symptom control as a single agent or may be added to octreotide LAR for rapid relief of symptoms or for breakthrough symptoms
c. GI Tract, Lung, and Thymus:
i. Treatment of underlying Zollinger-Ellison syndrome; OR
ii. Management of unresectable locoregional disease and/or distant metastases
1. as tumor control
2. as symptom control in patients with carcinoid syndrome
d. Poorly Differentiated (High-Grade)/Large or Small Cell
i. Consider for symptom control if somatostatin scintigraphy positive

i. Treatment for locally unresectable disease or distant metastases if somatostatin receptor positive imaging and symptomatic
D. Thymomas and Thymic Carcinomas
a. Second-line therapy with or without prednisone
E. For the control of diarrhea secondary to AIDS-associated enteropathy
F. Chemotherapy-induced diarrhea when the member has any of the following:
· Grade 3 or higher grade diarrhea according to National Cancer Institute (NCI)
· Grade 1 or 2 diarrhea according to National Cancer Institute (NCI) and tried and failed loperamide
G. For the treatment of portal hypertension and/or upper GI bleeding related to variceal bleeding in patients with esophageal varices
H. For the treatment of hypoglycemia in patients with congenital hyperinsulinism, including patients with benign or malignant insulinoma
I. TSH-producing pituitary adenomas associated with multiple endocrine neoplasia
J. Cluster Headache
K. Dumping syndrome
L. Enterocutenaous fistula
M. For the treatment of hepatorenal syndrome, in combination with midodrine and albumin
N. Ileostomy-associated diarrhea
O. Neurogenic orthostatic hypotension
P. For reducing output from a pancreatic fistula
Q. Short bowel syndrome

• Grade 1: Increase of <4 stools per day over baseline; mild increase in ostomy output compared to baseline
• Grade 2: Increase of 4 - 6 stools per day over baseline; moderate increase in ostomy output compared to baseline
• Grade 3: Increase of >=7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self care ADL
• Grade 4: Life-threatening consequences; urgent intervention indicate
• Grade 5: Death]

A. Neuroendocrine Tumors
a. Adrenal Gland Tumors
i. i. Used as treatment of symptoms of Cushing’s syndrome; AND
ii. Patient’s Cushing syndrome is not dependent upon adrenocorticotropic hormone (ACTH); AND
iii. Tumor is < 4 cm and has benign imaging characteristics; AND
iv. Patient has abnormal contralateral gland; AND
v. Patient has symmetric cortisol production per adrenal vein sampling; AND
vi. Patient is somatostatin receptor scintigraphy (OctreoScan) positive
b. Lung Neuroendocrine Tumors
i. Consider for stage IIIb (T4 due to multiple lung nodules), IV low, or intermediate-grade neuroendocrine carcinoma if octreotide scan positive or for symptoms of carcinoid syndrome
c. Neuroendocrine Tumors of the GI Tract, Lung, and Thymus
i. Treatment for underlying Zollinger-Ellison syndrome
ii. Management of unresectable locoregional disease and/or distant metastases as tumor control OR symptom control in patients with carcinoid syndrome
d. Neuroendocrine Tumors of the Pancreas
i. Treatment of symptoms related to hormone hypersecretion
ii. Consider for tumor control in patients with unresectable locoregional disease and/or metastatic disease and clinically significant tumor burden or clinically significant progression if not already given
e. Poorly Differentiated (High-Grade)/Large or Small Cell
i. Consider for symptom control if somatostatin scintigraphy positive
f. Pheochromocytoma/paraganglioma
i. Treatment for locally unresectable disease or distant metastases if somatostatin receptor positive imaging and symptomatic
B. Hyperthyroidism secondary to thyrotropinoma

· For prevention of postoperative pancreatic fistula, leak, or abscess in patients undergoing pancreaticoduodenectomy or distal pancreatetomy

There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL specifically for Sandostatin LAR depot (Octreotide), Somatuline Depo (lanreotide), Signifor LAR (pasireotide). Therefore, Medicare Advantage Products will cover Sandostatin LAR depot (Octreotide), Somatuline Depo (lanreotide), and Signifor LAR (pasireotide) when the Horizon policy criteria is met AND the drug is furnished and administered by a licensed medical provider as part of a physician service.

Per Local Coverage Article A53127 Self-Administered Drug Exclusion List, Medicare covers drugs that are furnished “incident to” a physician’s service provided that the drugs are medically reasonable and necessary, approved by the Food and Drug Administration (FDA) and are not usually administered by the patients who take them. Drugs that are ADMINISTERED subcutaneously are considered to be usually SELF-ADMINISTERED. If a drug is SELF-ADMINISTERED by more than 50 percent of Medicare beneficiaries, the drug is excluded from coverage. Per Local Coverage Article A53127, Sandostatin (non depot form) is self-administered and is therefore not covered.

For members with a Medicare drug plan (Part D) Sandostatin (non depot form) may be covered under that plan.

**Note: Bullet 1 of the policy section referring to Site of Administration for Infusion and Injectable Prescription Medications (Policy #142) does not apply for Medicare Advantage Products.
________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Sandostatin, Sandostatin LAR depot (Octreotide)
Sandostatin LAR depot
Octreotide
Somatuline
Signifor

References:

1. Vance ML, Harris AG. Long-term treatment of 189 acromegalic patients with the somatostatin analog octreotide. Results of the international multicenter acromegaly study group. Arch Intern Med 1991;151:1573–1578.

2. Ezzat S, Snyder PJ, Young WF, et al. Octreotide treatment of acromegaly: A randomized, multicenter study. Ann Intern Med 1992;117: 211–218.

3. Cozzi R, Montini M, Attanasio R, et al. Primary treatment of acromegaly with ocretotide LAR: a long-term (up to nine years) prospective study of its efficacy in the control of disease activity and tumor shrinkage. J Clin Endocrinol Metab 2006;91:1397–1403.

4. Cozzi R, Montini M, Attanasio R et al. Primary Treatment of Acromegaly with Octreotide LAR: A Long-Term (Up to Nine Years) Prospective Study of Its Efficacy in the Control of Disease Activity and Tumor Shrinkage. J Clin End Met 2006;4;91

5. Sandostatin LAR [prescribing information]. Novartis Pharmaceuticals, East Hanover, NJ. April 2019.

6. Sandostatin [prescribing information]. Novartis Pharmaceuticals, East Hanover, NJ. March 2012.
7. Sheehan AH, Yanovski JA, Calis KA. Chapter 86. Pituitary Gland Disorders. In: Wells BG, ed. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=7992629. Accessed December 26, 2013.

8. Taylor A. Follow Up Adverse Event Review: Octreotide. Pediatric Advisory Committee Meeting. November 2008. Available at http://www.fda.gov/ohrms/dockets/ac/08/slides/2008-4399s1-12%20(Octreotide).pdf

9. National Comprehensive Cancer Network (NCCN). NCCN Drug & Biologics Compendium – Octreotide Acetate. Available at http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=164 (Accessed July 30, 2020)

10. National Comprehensive Cancer Network (NCCN). NCCN Drug & Biologics Compendium – Octreotide Acetate LAR. Available at http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=173 (Accessed July 30, 2020)

11. Somatuline Depot [prescribing information]. Ipsen Biopharmaceuticals, Basking Ridge, NJ. April 2019.

12. Signifor LAR [prescribing information]. Novartis Pharmaceuticals, East Hanover, NJ. April 2019.

13. National Comprehensive Cancer Network (NCCN). NCCN Drug & Biologics Compendium – Lanreotide. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=38 (Accessed July 30, 2020)

14. Clinical Pharmacology. Lanreotide. Available at: https://clinicalpharmacology.com/Forms/Monograph/monograph.aspx?cpnum=3580&sec=monindi&t=0 (Accessed July 30, 2020).

15. Didden P, Penning C, & Masclee AA: Octreotide therapy in dumping syndrome: analysis of long-term results. Aliment Pharmacol Ther 2006; 24(9):1367-1375.

16. Glaser B, Rosler A, & Halperin Y: Chronic treatment of a benign insulinoma using the long-acting somatostatin analogue SMS 201-995. Isr J Med SCi 1990; 26:16-19.

17. Carcoforo P, Soliani G, Maestroni U, et al: Octreotide in the treatment of lymphorrhea after axillary node dissection: a prospective randomized controlled trial. J Am Coll Surg 2003; 196(3):365-369.

18. Piaditis GP, Hatziioanidis AH, Trovas GP, et al: The effect of sequential administration of octreotide alone and octreotide/growth hormone simultaneously on buserelin stimulated ovarian steroid secretion in women with polycystic ovary syndrome. Clin Endocrinol 1996; 45:595-604.

19. Yavuz MN, Yavuz AA, Aydin F, et al: The efficacy of octreotide in the therapy of acute radiation-induced diarrhea: a randomized controlled study. Int J Radiat Oncol Biol Phys 2002; 54(1):195-202.

20. Barbounis V, Koumakis G, Vassilomanolakis M, et al: Control of irinotecan-induced diarrhea by octretide after loperamide failure. Support Care Cancer 2001; 9:258-260.

21. Schiedermaier P, Harrison P, Arthur M, et al: Effect of the somatostatin analogue lanreotide on meal-stimulated portal blood flow in patients with liver cirrhosis. Digestion 2002; 65:56-60.

22. Fiedler F, Jauernig G, Keim V, et al: Octreotide treatment in patients with necrotizing pancreatitis and pulmonary failure. Intensive Care Med 1996; 22:909-915.

23. Geffner ME, Nagel RA, Dietrich RB, et al: Treatment of acromegaly with a somatostatin analog in a patient with McCune-Albright syndrome. J Pediatrics 1987; 111:740-743.

24. Pallmieri G, Colao A, Varrella P, et al: Successful treatment of a patient with a thymoma and pure red-cell aplasia with octreotide and prednisone. N Engl J Med 1997; 336:263-265.

25. US Department of Health and Human Services. Common terminology criteria for adverse events

(CTCTAE). v4.03. 06/14/2010. Available at: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Accessed April 29, 2017.