COSA:NETs guidelines/Short and Long-Acting Somatostatin Analogues (SSA)

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Short and Long-Acting Somatostatin Analogues (SSA)

The role of SSAs for the amelioration of symptoms of the carcinoid syndrome from functional GEP NETs is well established. The two main groups of agents currently available in Australia, octreotide and lanreotide, have not been directly compared; both are available in short and long acting preparations, but their administration differs. Lanreotide is not available in New Zealand.

Anti-proliferative activity of the SSAs has been suggested by trials with both octreotide and lanreotide. Initially results were available with octreotide LAR in patients with well-differentiated low proliferative index metastatic midgut NETs, whether symptomatic or asymptomatic, having a significantly longer progression-free survival when treated with octreotide LAR compared to placebo.[1] These data however have their limitations,[2] but more recently lanreotide autogel has a demonstrated a similar benefit in patients with midgut NETs, but also patients with pancreatic NETs. This study included NETs with proliferative indices (Ki67) of up to 10%.[2] Together these studies support an anti-proliferative benefit from this class of drugs, although the optimal timing for commencement of SSA treatment is still unknown.

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Definite indications

  • Treatment of patients with symptomatic carcinoid syndrome. The indications for SSA therapy may be wider than specified by Medicare for Pharmaceutical Benefits Scheme subsidised treatment, however treatment may not be reimbursed if those criteria are not met.
  • Prevention or treatment of carcinoid crisis as part of the perioperative management of patients with GEP NETs.[3] Prophylactic cover with SSAs is preferred in patients considered at risk of carcinoid crisis undergoing surgery. Some patients may also be at risk when commencing peptide receptor radionuclide therapy or chemotherapy.
  • SSA therapy is an option for patients with progressing well-differentiated metastatic midgut and pancreatic NETs, regardless of the presence or absence of the carcinoid syndrome. The recommended starting doses when used as anti-proliferative treatment, based on the available randomized trials evidence, are octreotide LAR 30mg or lanreotide autogel 120mg given every four weeks.[1][2] Octreotide LAR has been approved by the Therapeutic Goods Administration and MedSafe for the treatment of these patients with progressing disease. However, at present these patients may not qualify for PBS reimbursed treatment unless the PBS indications are met. In New Zealand SSAs are also not funded in the absence of carcinoid syndrome. Alternatively it may be reasonable to observe asymptomatic patients and to commence SSA therapy upon clinically significant disease progression.
  • Treatment of symptomatic vasoactive intestinal peptide secreting tumours (VIPomas).

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Possible indications

  • Prevention of the development of carcinoid syndrome related fibrotic disease.

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Practical points

  • A benefit from SSA therapy may be predicted by somatostatin scintigraphy (e.g. 111Indium Octreoscan).
  • It may be useful to initially commence patients on a short acting SSA to assess treatment tolerability before converting to a long acting preparation.
  • A common practice based on anecdotal experience is to escalate the SSA dose or increase the frequency of administration of the long acting agents as this may overcome primary or secondary treatment resistance. However only standard dose therapy is reimbursed by the PBS.
  • Long-acting SSA therapy should be withheld at least four weeks prior to somatostatin scintigraphy. Patients who are intolerant of an interruption of SSA therapy may be managed with short-acting agents, which can be ceased close to the time of the scan.
  • See "Peri-operative Management" in the Surgery section of these guidelines for further information on use of SSAs for peri-operative management and prevention of carcinoid crisis.

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References

  1. 1.0 1.1 Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, et al. Placebo-controlled, double-blind, prospective, randomized 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 Oct 1;27(28):4656-63 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19704057].
  2. 2.0 2.1 2.2 Caplin M, Ruszniewski P, Pavel M, Ćwikła JB, Phan A, Raderer M, et al. A randomized double-blind placebo-controlled study of lanreotide antiproliferative response In patients with enteropancreatic neuroendocrine tumours (CLARINET). Eur J Cancer 2013 [cited 2014 Jun 12];49(3):Abstract E17-7103.
  3. Oberg K, Kvols L, Caplin M, Delle Fave G, de Herder W, Rindi G, et al. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol 2004 Jun;15(6):966-73 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15151956].


Further Readings

  • Chua YJ, Michael M, Zalcberg JR, Hicks RJ, Goldstein D, Liauw W, et al. Antitumor effect of somatostatin analogs in neuroendocrine tumors J Clin Oncol 2010 Jan 20;28(3):e41-2; author reply e43-4 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20008618].
  • National Comprehensive Cancer Network. Neuroendocrine tumors (version 2). NCCN Clinical Practice Guidelines in Oncology 2009.


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