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Approaches to Treatment of NETs

Neuroendocrine tumours (NETs) may be treated with surgical resection of the tumour (local disease) and regional nodal or hepatic metastases, somatostatin analogue therapy, chemotherapy, and interferon therapy.

Surgery

ENETS guidelines recommend surgery as the primary treatment for localised tumours. For such tumours, surgery is potentially curative, giving 5-year survival rates of 80% to 100%. In metastatic disease, the role of surgery is to reduce tumour mass and can be performed before or concurrently with medical treatment for patients with functioning tumours.^1,2

Chemotherapy, Radiation, and Interferon Therapy

Although chemotherapy is standard for endocrine pancreatic tumours, it has only a modest effect on low-proliferating GEP NETs. Its use therefore depends on the type of tumour and its level of differentiation. For patients with tumours that express a high number of somatostatin receptors determined by Octreoscan™, tumour-targeted radiation therapy may be an option. In patients with functioning tumours, interferon therapy has shown efficacy in controlling symptoms of carcinoid syndrome related to hormone release.^1,2

Somatostatin Analogues

Somatostatin analogues, which are synthetic forms of somatostatin such as octreotide, work at the site of the tumour and bind to sst-2/sst-5 receptors to regulate gastrointestinal hormone secretion and affect tumour growth.^3-5 See below for more information on somatostatin analogue therapy (link to “Somatostatin Analogue Therapy” on bottom of same page).

Somatostatin Analogue Therapy

Somatostatin and somatostatin analogues are proven first-choice medications for the control of symptoms that occur from overproduction of hormones. These drugs work at the site of NETs to control their secretion, and in some cases delay their growth. Octreotide is a synthetic form of somatostatin used in the treatment of GEP NETs and carcinoid syndrome. It blocks the release of bioactive substances from carcinoid tumours, prolongs intestinal transit time, and increases water and electrolyte absorption, significantly reducing symptoms of diarrhoea and flushing.

A long-acting, slow-release form of octreotide (Sandostatin^® LAR^®, Novartis Pharma AG) is available for the treatment of symptoms of GEP NETs and carcinoid syndrome. Administered intramuscularly once a month, it is as efficacious as the standard formulation of octreotide (Sandostatin Injection, used 3 times daily) in suppressing symptoms due to GEP NETs.⁶ Sandostatin Injection has been used as a safe and effective treatment for GEP NETs and carcinoid syndrome for the past 10 years, and is the most prescribed⁷ and most studied⁸ medical therapy for GEP NETs. To date, Sandostatin has been discussed in more than 6000 scientific publications.

Sandostatin LAR provides powerful efficacy for the control of the symptoms associated with NETs.

In summary, management of the patient with NETs involves treating the symptoms as well as the tumours. Surgical removal of the tumours may lead to symptom relief and a cure; however, many patients will face an ongoing battle with metastatic disease. Controlling symptoms requires periodic testing of hormone levels and tumour markers, as well as possible adjustment of medication.

The algorithm above illustrates the balance of treatments necessary for good management.

References: 1. Plockinger U, Rindi G, Arnold R, et al. Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology. 2004;80:394-424. 2. Oberg K, Jelic S; on behalf of the ESMO Guidelines Working Group. Neuroendocrine gastroenteropancreatic tumors: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2008;19(suppl 2):ii104-ii105. 3. Benali N, et al. Somatostatin receptors. Digestion. 2000;62:27-32. 4. Battershill PE, et al. Octreotide: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in conditions associated with excessive peptide secretion. Drugs. 1989;38:658-702. 5. Arnold R, et al. Somatostatin analogue octreotide and inhibition of tumour growth in metastatic endocrine gastroenteropancreatic tumours. Gut. 1996;38:430-438. 6. Arnold R. Diagnosis and Management of Neuroendocrine Tumors. 8th United European Gastroenterology Week, 2001. 7. Scott-Levin's Physician Drug & Diagnosis Audit (PDDA) from Verispan, September 1996-August 2002. 8. PubMed [database online]. National Center for Biotechnology Information. Available at http://www.ncbi.nlm.nih.gov/sites/gquery?term=sandostatin. Accessed March 19, 2009. 9. Norton JA, Levin B, Jensen RT. Cancer of the endocrine system. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles & Practice of Oncology. 4th ed. Philadelphia, PA: JB Lippincott; 1993;2:1333-1435.⁹