Pasireotide in the treatment of neuroendocrine tumors: a review of the literature

2018 ◽  
Vol 25 (6) ◽  
pp. R351-R364 ◽  
Author(s):  
Giovanni Vitale ◽  
Alessandra Dicitore ◽  
Concetta Sciammarella ◽  
Sergio Di Molfetta ◽  
Manila Rubino ◽  
...  

Somatostatin analogs have an important role in the medical therapy of neuroendocrine tumors (NETs). Octreotide and lanreotide, both somatostatin analogs binding with high affinity for the somatostatin receptor (SSTR)2, can control symptoms in functional NETs. In addition, these compounds, because of their antiproliferative effects, can stabilize growth of well-differentiated NETs. Pasireotide is a novel multireceptor-targeted somatostatin analog with high affinity for SSTR1, 2, 3, and 5. This review provides an overview of the state of the art of pasireotide in the treatment of NETs, with the aim of addressing clinical relevance and future perspectives for this molecule in the management of NETs.

2021 ◽  
Vol 12 ◽  
Author(s):  
Mayank Patel ◽  
Isabel Tena ◽  
Abhishek Jha ◽  
David Taieb ◽  
Karel Pacak

Neuroendocrine tumors overexpress somatostatin receptors, which serve as important and unique therapeutic targets for well-differentiated advanced disease. This overexpression is a well-established finding in gastroenteropancreatic neuroendocrine tumors which has guided new medical therapies in the administration of somatostatin analogs, both “cold”, particularly octreotide and lanreotide, and “hot” analogs, chelated to radiolabeled isotopes. The binding of these analogs to somatostatin receptors effectively suppresses excess hormone secretion and tumor cell proliferation, leading to stabilization, and in some cases, tumor shrinkage. Radioisotope-labeled somatostatin analogs are utilized for both tumor localization and peptide radionuclide therapy, with 68Ga-DOTATATE and 177Lu-DOTATATE respectively. Benign and malignant pheochromocytomas and paragangliomas also overexpress somatostatin receptors, irrespective of embryological origin. The pattern of somatostatin receptor overexpression is more prominent in succinate dehydrogenase subunit B gene mutation, which is more aggressive than other subgroups of this disease. While the Food and Drug Administration has approved the use of 68Ga-DOTATATE as a radiopharmaceutical for somatostatin receptor imaging, the use of its radiotherapeutic counterpart still needs approval beyond gastroenteropancreatic neuroendocrine tumors. Thus, patients with pheochromocytoma and paraganglioma, especially those with inoperable or metastatic diseases, depend on the clinical trials of somatostatin analogs. The review summarizes the advances in the utilization of somatostatin receptor for diagnostic and therapeutic approaches in the neuroendocrine tumor subset of pheochromocytoma and paraganglioma; we hope to provide a positive perspective in using these receptors as targets for treatment in this rare condition.


2021 ◽  
Vol 60 (2) ◽  
Author(s):  
Francesca SANGUEDOLCE ◽  
Magda ZANELLI ◽  
Stefano ASCANI ◽  
Maurizio ZIZZO ◽  
Simona TORTORELLA ◽  
...  

2019 ◽  
Vol 37 (28) ◽  
pp. 2571-2580 ◽  
Author(s):  
Alberto Carmona-Bayonas ◽  
Paula Jiménez-Fonseca ◽  
Ángela Lamarca ◽  
Jorge Barriuso ◽  
Ángel Castaño ◽  
...  

PURPOSE Somatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients. PATIENTS AND METHODS We extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom). RESULTS We recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively. CONCLUSION The GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in daily clinical practice.


2014 ◽  
Vol 1 (2) ◽  
pp. 195-201
Author(s):  
Christine Wurst ◽  
Karin Jandt ◽  
Silke Schuele ◽  
Falk Rauchfuß ◽  
Utz Settmacher

2020 ◽  
Vol 9 (7) ◽  
pp. 2203 ◽  
Author(s):  
Maria Isabel del Olmo-García ◽  
Maria Angustias Muros ◽  
Martín López-de-la-Torre ◽  
Marc Agudelo ◽  
Pilar Bello ◽  
...  

Neuroendocrine tumors (NETs) frequently overexpress somatostatin receptors (SSTR) on their cell surface. The first-line pharmacological treatment for inoperable metastatic functioning well-differentiated NETs are somatostatin analogs. On second line, Lu-DOTA-TATE (177Lu-DOTA0 Tyr 3 octreotate) has shown stabilization of the disease and an increase in progression free survival, as well as effectiveness in controlling symptoms and increasing quality of life. The management of functional NETs before and during LU-DOTA-TATE treatment is specially challenging, as several complications such as severe carcinoid and catecholamine crisis have been described. The aim of this review is to establish practical guidance for the management and prevention of the most common hormonal crises during radionuclide treatment with Lu-DOTA-TATE: carcinoid syndrome (CS) and catecholamine hypersecretion, as well as to provide a brief commentary on other infrequent metabolic complications. To establish a practical approach, a systematic review was performed. This systematic review was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and conducted using MEDLINE (accessed from PubMed), Google Scholar and ClinicalTrials.gov. Literature searches found 449 citations, and finally nine were considered for this systematic review.


2010 ◽  
Vol 17 (1) ◽  
pp. R53-R73 ◽  
Author(s):  
Dik J Kwekkeboom ◽  
Boen L Kam ◽  
Martijn van Essen ◽  
Jaap J M Teunissen ◽  
Casper H J van Eijck ◽  
...  

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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