Antiproliferative effect of somatostatin analogs in gastroenteropancreatic neuroendocrine tumors

Neuroendocrine tumors (NETs) have increased in incidence and prevalence over the past 2 decades and affect approximately 170,000 people in the United States alone. Gastroenteropancreatic (GEP) NETs (GEP NET) are a heterogeneous group of rare tumors that have distinct effects on the body due to their tumor location and potential to secrete hormones and peptides. Clinical practice guidelines and consensus guidelines for GEP NETs with regard to best practice for diagnosis, treatment, and medical management are available, but the supportive care needs and optimal nutritional management of patients affected by these unique tumors remain under-researched: evidence to guide clinical practice is lacking. The pathophysiology of the disease and its treatment can cause various symptoms that can have significant effects on vitamin synthesis and absorption, dietary habits, weight change, and appetite. Deficiency of fat-soluble vitamins and niacin exists amongst patients with GEP NET, particularly those on treatment with somatostatin analogs and with serotonin-secreting tumors, respectively. Malnutrition and dietary modification amongst patients with GEP NET is more prevalent than initially thought: up to 25% of inpatients with GEP NET are malnourished. Food intolerance is also reported in up to 40–90% of these patients, though its misdiagnosis is common. This review summarizes the evidence regarding the impact of GEP NET and its treatment on nutritional factors in these patients with emphasis on malnutrition, vitamin deficiencies, dietary intake, and quality of life. Recommendations for clinical practice and research approaches to address these nutritional issues are discussed.

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2311 Evaluation of predictive factors of efficacy of Somatostatin Analogs (SSA) in Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET): a single centre experience

European Journal of Cancer ◽

10.1016/s0959-8049(16)31227-8 ◽

2015 ◽

Vol 51 ◽

pp. S436

Author(s):

R. Marconcini ◽

S. Ricci ◽

L. Galli ◽

A. Antonuzzo ◽

E. Vasile ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Predictive Factors ◽

Somatostatin Analogs ◽

Single Centre ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Single Centre Experience

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Management Options for Advanced Low or Intermediate Grade Gastroenteropancreatic Neuroendocrine Tumors: Review of Recent Literature

International Journal of Surgical Oncology ◽

10.1155/2017/6424812 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 1

Author(s):

Vladimir Neychev ◽

Electron Kebebew

Keyword(s):

Neuroendocrine Tumors ◽

Tryptophan Hydroxylase ◽

Management Strategies ◽

Somatostatin Analogs ◽

Treatment Strategies ◽

Peptide Receptor Radionuclide Therapy ◽

Phase Iii ◽

Management Options ◽

Intermediate Grade ◽

Gastroenteropancreatic Neuroendocrine Tumors

Our understanding of the biology, genetics, and natural history of neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas has improved considerably in the last several decades and the spectrum of available therapeutic options is rapidly expanding. The management of patients with metastatic low or intermediate grade NETs has been revolutionized by the development of new treatment strategies such as molecular targeting therapies with everolimus and sunitinib, somatostatin analogs, tryptophan hydroxylase inhibitors, and peptide receptor radionuclide therapy that can be used alone or as a multimodal approach with or without surgery. To further define and clarify the utility, appropriateness, and the sequence of the growing list of available therapies for this patient population will require more high level evidence; however, data from well-designed randomized phase III clinical trials is rapidly accumulating that will further stimulate development of new management strategies. It is therefore important to thoroughly review emerging evidence and report major findings in frequent updates, which will expand our knowledge and contribute to a better understanding, characterization, and management of advanced NETs.

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Somatostatin receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors

Endocrine Related Cancer ◽

10.1677/erc-09-0078 ◽

2010 ◽

Vol 17 (1) ◽

pp. R53-R73 ◽

Cited By ~ 257

Author(s):

Dik J Kwekkeboom ◽

Boen L Kam ◽

Martijn van Essen ◽

Jaap J M Teunissen ◽

Casper H J van Eijck ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Pet Imaging ◽

Tumor Regression ◽

Somatostatin Receptor ◽

Somatostatin Analogs ◽

Receptor Subtype ◽

Receptor Imaging ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Pet Tracer ◽

First Choice

Somatostatin receptor imaging (SRI) with [111In-DTPA0]octreotide has proven its role in the diagnosis and staging of gastroenteropancreatic neuroendocrine tumors (GEPNETs). Newer radiolabeled somatostatin analogs which can be used in positron emission tomography (PET) imaging, and which have a higher affinity for the somatostatin receptor, especially receptor subtype-2, have been developed. It would be desirable, however, if one radiolabeled analog became the new standard for PET imaging, because the current application of a multitude of analogs implies a fragmented knowledge on the interpretation of the images that are obtained in clinical practice. In our view, the most likely candidates for such a universal PET tracer for SRI are [68Ga-DOTA0,Tyr3]octreotate or [68Ga-DOTA0,Tyr3]octreotide. Treatment with radiolabeled somatostatin analogs is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumors. Symptomatic improvement may occur with all 111In-, 90Y-, or 177Lu-labeled somatostatin analogs that have been used for peptide receptor radionuclide therapy (PRRT). The results that were obtained with [90Y-DOTA0,Tyr3]octreotide and [177Lu-DOTA0,Tyr3]octreotate are very encouraging in terms of tumor regression. Also, if kidney protective agents are used, the side effects of this therapy are few and mild, and the median duration of the therapy response for these radiopharmaceuticals is 30 and 40 months respectively. The patients' self-assessed quality of life increases significantly after treatment with [177Lu-DOTA0,Tyr3]octreotate. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with [177Lu-DOTA0,Tyr3]octreotate. These data compare favorably with the limited number of alternative treatment approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable GEPNETs.

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Role of Endoscopic Ultrasound in Gastroenteropancreatic Neuroendocrine Tumors and Update on Their Treatment

Journal of Postgraduate Medicine Education and Research ◽

10.5005/jp-journals-10028-1056 ◽

2013 ◽

Vol 47 (1) ◽

pp. 54-60

Author(s):

Vishal Sharma ◽

Surinder Singh Rana ◽

Deepak Kumar Bhasin

Keyword(s):

Neuroendocrine Tumors ◽

Endoscopic Ultrasound ◽

Imaging Techniques ◽

Somatostatin Analogs ◽

Neuroendocrine Cells ◽

Molecular Therapy ◽

Long Term Results ◽

Gi Tract ◽

Gastroenteropancreatic Neuroendocrine Tumors

ABSTRACT The gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are rare tumors and include all tumors arising from the gastrointestinal (GI) or pancreatic neuroendocrine cells. They can occur anywhere in the GI tract with the small intestine, pancreas and rectum being the common GI sites. Because of nonspecific symptoms they are difficult to diagnose and diagnosis is often delayed by years. Advancement in cross-sectional imaging techniques and advent of radionuclide-labeled somatostatin analogs have improved our accuracy of diagnosis and staging GEP NETs. Endoscopic ultrasound (EUS) with its unique combination of endoscopy and ultrasound provides high resolution images of GI tract wall as well as the surrounding solid parenchymal organs and therefore is an important investigation for the diagnosis and staging of GEP NETs. Surgery is the treatment of choice with good long-term results in patients with localized GEP-NETs. Control of symptoms in functional NETs is warranted to improve the quality of life of the patient. Somatostatin and its analogs like octreotide and lanreotide have been used to control symptoms because of functional NETs. The management of metastatic GEP NETs includes control of symptoms and therapy to decrease/stop tumor growth that includes somatostatin and its analogs and chemotherapy. Newer therapeutic modalities like peptide receptor radionuclide therapy (PRRT) and molecular therapy hold considerable promise. How to cite this article Rana SS, Sharma V, Bhasin DK. Role of Endoscopic Ultrasound in Gastroenteropancreatic Neuroendocrine Tumors and Update on Their Treatment. J Postgrad Med Edu Res 2013;47(1):54-60.

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GEP–NETs UPDATE: Radionuclide therapy in neuroendocrine tumors

Acta Endocrinologica ◽

10.1530/eje-14-0488 ◽

2015 ◽

Vol 172 (1) ◽

pp. R1-R8 ◽

Cited By ~ 60

Author(s):

Wouter A van der Zwan ◽

Lisa Bodei ◽

Jan Mueller-Brand ◽

Wouter W de Herder ◽

Larry K Kvols ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Targeted Therapies ◽

Radionuclide Therapy ◽

Randomized Clinical Trials ◽

Treatment Options ◽

Objective Response ◽

Somatostatin Analogs ◽

Peptide Receptor Radionuclide Therapy ◽

Treatment Modalities ◽

Gastroenteropancreatic Neuroendocrine Tumors

Peptide receptor radionuclide therapy (PRRT) is a promising new treatment modality for inoperable or metastasized gastroenteropancreatic neuroendocrine tumors (GEPNETs) patients. Most studies report objective response rates in 15–35% of patients. Also, outcome in terms of progression free survival (PFS) and overall survival compares very favorably with that for somatostatin analogs, chemotherapy, or new, ‘targeted’ therapies. They also compare favorably to PFS data for liver-directed therapies. Two decades after the introduction of PRRT, there is a growing need for randomized controlled trials comparing PRRT to ‘standard’ treatment, that is treatment with agents that have proven benefit when tested in randomized trials. Combining PRRT with liver-directed therapies or with targeted therapies could improve treatment results. The question to be answered, however, is whether a combination of therapies performed within a limited time-span from one another results in a better PFS than a strategy in which other therapies are reserved until after (renewed) tumor progression. Randomized clinical trials comparing PRRT with other treatment modalities should be undertaken to determine the best treatment options and treatment sequelae for patients with GEPNETs.

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Somatostatin analogs in association with peptide receptor radionucleotide therapy in advanced well-differentiated NETs

Future Oncology ◽

10.2217/fon-2019-0138 ◽

2019 ◽

Vol 15 (26) ◽

pp. 3015-3024

Author(s):

Natalie Prinzi ◽

Alessandra Raimondi ◽

Marco Maccauro ◽

Massimo Milione ◽

Enrico Garanzini ◽

...

Keyword(s):

Overall Survival ◽

Neuroendocrine Tumors ◽

Somatostatin Analogs ◽

Progression Free Survival ◽

Hazard Ratio ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Free Survival ◽

Peptide Receptor ◽

Treatment Beyond Progression ◽

Well Differentiated

Aim: Data from 69 well-differentiated gastroenteropancreatic neuroendocrine tumors treated with peptide receptor radionucleotide therapy + somatostatin analogs (SSAs) after SSA treatment failure were evaluated. Methods: We identified two groups: S1 – patients who kept the same SSA treatment beyond progression; S2 – patients who switched the SSA with another SSA after progression. Results: Median progression-free survival was 53 and 127 months in S1 and S2, respectively (p = 0.001; hazard ratio: 0.31; 95% CI: 0.15–0.63). Median overall survival was 69 versus 150 months in S1 and S2, respectively (p = 0.004; hazard ratio: 0.32; 95% CI: 0.14–0.71). Conclusion: In patients with advanced well-differentiated gastroenteropancreatic neuroendocrine tumors treated with peptide receptor radionucleotide therapy plus SSA after SSA failure, the ‘switch’ strategy of SSA after progression improve progression-free survival and overall survival.

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