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Neuroendocrine Tumours Octreotide – A Review of its Use in Treating Neuroendocrine Tumours Frederico Costa 1 and Brenda Gumz 2 1. Medical Oncologist; 2. Physician, Oncology Centre, Hospital Sírio-Libanês, São Paulo, Brazil Abstract Neuroendocrine tumours (NETs) are a heterogeneous group of neoplasms whose incidence has dramatically increased in recent years. Octreotide is a somatostatin analogue used in the treatment of NETs, and its use in clinical trials has been associated with substantially increased survival. Although traditionally used for the relief of symptoms that result from release of peptides and neuroamines, there has been a growing body of evidence that suggest octreotide has antiproliferative effects. A phase III clinical study has demonstrated that the long-acting formulation (LAR), octreotide LAR, lengthens time to tumour progression in patients with well-differentiated metastatic midgut NETs, and that octreotide LAR is a treatment option for patients with metastatic midgut NETs, regardless of functional status. Furthermore, octreotide LAR has demonstrated clinical efficacy in different types of NETs. These data, along with emerging data on somatostatin analogs, may change the way doctors approach this patient population and reinforce the use of these drugs as a treatment option for patients with non-functioning tumours. Keywords Neuroendocrine tumours, octreotide, somatostatin analogues Disclosure: The authors have no conflicts of interest to declare. Acknowledgements: Editorial assistance was provided by Katrina Mountfort at Touch Medical Media. Received: 16 October 2013 Accepted: 26 November 2013 Citation: European Oncology & Haematology, 2013;9(2):105–9 Correspondence: Frederico Costa, Oncology Center, Hospital Sírio-Libanês, Adma Jafet Street, 91, São Paulo, SP, 0138-050, Brazil. E: Support: The publication of this article was supported by Novartis. The views and opinions expressed are those of the authors and not necessarily those of Novartis. Neuroendocrine tumours (NETs) is a collective term for a diverse range of neoplasms that arise from cells that originate in the endocrine and nervous systems and share common morphological and immunohistochemical features, including the presence of secretory granules. These tumours can secrete a variety of neuropeptides, which may or may not cause characteristic hormonal symptoms (functioning or non-functioning NETs). NETs have generally been considered rare; their incidence has been estimated at 2.5 to 5 per 100,000 people per year and prevalence of 35 per 100,000 1 and may be higher if undiagnosed NETs are included. Autopsy studies have indicated that pancreatic NETs (pNETs) occur in 0.8  % to 10  % of patients undergoing a post-mortem examination. 2 However, data from the largest US epidemiological database (SEER) indicate that the incidence of gastroenteropancreatic NETs (GEP-NETs ) is increasing dramatically in the US: a fivefold increase has been reported between 1973 and 2004 (see Figure 1). The incidence of GEP-NETs has risen steeply since 1992, and more than doubled since 1985. 3 This is in contrast to the overall incidence of malignant neoplasms, which has remained relatively consistent since 1992. NETs of the lung, rectum and small intestine are currently the most frequently diagnosed NETs in the US and are also the three subgroups of NETs that have increased in incidence by the greatest margin from 1973 to 2004. 3 The age-adjusted incidence of NETs of the small intestine and digestive system has increased by 460 % and 720 %, respectively, over the past 30 years. 4 NETs that secrete peptides and neuroamines can cause recognisable clinical syndromes, including carcinoid syndrome. 4 However, due to © To u ch MEd ica l MEdia 2013 the indolent nature of NETs, many patients are asymptomatic in the early stages, or present with only vague symptoms such as abdominal pain. 4 As a result, NETs are frequently metastatic at the time of diagnosis: liver metastases are observed in 40  % of patients who present with small intestinal and 60–70  % of patients with pNETS. 3,5 Other factors influencing the presence of liver metastases include the primary tumour site, tumour stage, histological differentiation and proliferative activity (grading; G1–G3). Carcinoid syndrome is frequently associated with distant metastases, especially in the liver. The prognosis for NETs varies according to proliferative activity: median survival in distant metastatic disease was 33 months in patients with G1–G2 graded NETs, but only 5 months in patients with poorly differentiated carcinomas. 3 The 5-year survival rate was 35 % in well to moderately differentiated (grade 1/2) NETs, but less than 5 % in poorly differentiated grade 3 NETs. 3 The first-line treatment strategy for NETs is surgery, but this is rarely curative, as most patients present at advanced stages of disease. 3,5 Other treatment options include cytoreduction, radiological intervention (by embolisation and radiofrequency ablation) and chemotherapy. 4 Surgical debulking can reduce the extent of hormone production and relieve symptoms, but owing to the long disease course, palliative care is important. Somatostatin analogues (SSAS), including octreotide and lanreotide, were introduced to control symptoms that result from release of peptides and neuroamines. Octreotide is the most studied SSA. This article aims to review the 25 years of clinical experience with octreotide in treatment of NETs. 105