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https://www.readbyqxmd.com/read/29205458/multi-disciplinary-management-of-refractory-insulinomas
#1
Emily Brown, Daniel Watkin, Jonathan Evans, Vincent Yip, Daniel J Cuthbertson
Insulinomas are predominantly benign (~90%), pancreatic neuroendocrine tumours characterised by hyperinsulinaemic hypoglycaemia. They usually present as a small (<2cm), well demarcated, solitary nodule that can arise in any part of the organ. Treatment of sporadic insulinomas is generally aimed at curative surgical resection with special consideration in genetic syndromes. Patients with significant hypoglycaemia can pose a difficult management challenge. In isolated cases where the patient is not medically fit for surgery or with metastatic spread, other treatment options are employed...
December 4, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/29196939/clinical-and-functional-implication-of-the-components-of-somatostatin-system-in-gastroenteropancreatic-neuroendocrine-tumors
#2
Aura D Herrera-Martínez, Manuel D Gahete, Sergio Pedraza-Arevalo, Rafael Sánchez-Sánchez, Rosa Ortega-Salas, Raquel Serrano-Blanch, Raúl M Luque, María A Gálvez-Moreno, Justo P Castaño
PURPOSE: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) comprise a heterogeneous group of malignancies often presenting with metastasis at diagnosis and whose clinical outcome is difficult to predict. Somatostatin (SST) analogs (SSAs) provide a valuable pharmacological tool to palliate hormonal symptoms, and control progression in some NETs. However, many patients do not respond to SSAs or develop resistance, and there are many uncertainties regarding pathophysiology of SST and its receptors (sst1-sst5) in GEP-NETs...
December 1, 2017: Endocrine
https://www.readbyqxmd.com/read/29155991/efficacy-and-safety-of-switching-to-pasireotide-in-acromegaly-patients-controlled-with-pegvisomant-and-first-generation-somatostatin-analogues-pape-study
#3
Ammar Muhammad, Aart J van der Lely, Patric J D Delhanty, Alof H G Dallenga, Iain K Haitsma, Joseph A M J L Janssen, Sebastian J C M M Neggers
Aim: To assess the efficacy and safety of pasireotide long-acting release (PAS-LAR) alone or in combination with pegvisomant by switching acromegaly patients who were well-controlled with somatostatin analogues (LA-SSAs) and pegvisomant to PAS-LAR with or without pegvisomant. Methods: 61 acromegaly patients were enrolled in a prospective open-label study. We included patients with an IGF-I ≤1.2 x Upper Limit of Normal (ULN) during treatment with LA-SSAs and pegvisomant...
November 15, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29133263/prospective-evaluation-of-pasireotide-in-patients-undergoing-pancreaticoduodenectomy-the-washington-university-experience
#4
Ismael Dominguez-Rosado, Ryan C Fields, Cheryl A Woolsey, Gregory Williams, Timothy A Horwedel, J Bart Rose, Chet W Hammill, Maria B Doyle, William C Chapman, Steven M Strasberg, William G Hawkins, Dominic E Sanford
BACKGROUND: Pasireotide is a newer generation somatostatin analogue which led to a significant reduction in pancreatic fistula after pancreatectomy in a single-center randomized controlled trial. We sought to determine if pasireotide reduces the incidence of pancreatic fistula and other complications following pancreaticoduodenectomy at our high volume center. STUDY DESIGN: All patients between April 2011 and January 2017 undergoing pancreaticoduodenectomy were prospectively followed and their complications graded using the Modified Accordion Grading System (MAGS) in our institutional complications database...
November 10, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/29074099/efficacy-and-safety-of-long-acting-pasireotide-or-everolimus-alone-or-in-combination-in-patients-with-advanced-carcinoids-of-the-lung-and-thymus-luna-an-open-label-multicentre-randomised-phase-2-trial
#5
Piero Ferolla, Maria Pia Brizzi, Tim Meyer, Wasat Mansoor, Julien Mazieres, Christine Do Cao, Hervé Léna, Alfredo Berruti, Vincenzo Damiano, Wieneke Buikhuisen, Henning Grønbæk, Catherine Lombard-Bohas, Christian Grohé, Vincenzo Minotti, Marcello Tiseo, Javier De Castro, Nicholas Reed, Gabriella Gislimberti, Neha Singh, Miona Stankovic, Kjell Öberg, Eric Baudin
BACKGROUND: There are no data from prospective studies focused exclusively on patients with advanced lung and thymic carcinoids. We aimed to assess the efficacy and safety of long-acting pasireotide and everolimus, administered alone or in combination, in patients with advanced carcinoids of the lung or thymus. METHODS: LUNA was a prospective, multicentre, randomised, open-label, phase 2 trial of adult patients (aged >18 years) with advanced (unresectable or metastatic), well differentiated carcinoid tumours of the lung or thymus, with radiological progression within 12 months before randomisation, and a WHO performance status of 0-2...
October 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29067877/somatostatin-analogs-in-the-treatment-of-neuroendocrine-tumors-current-and-emerging-aspects
#6
Gherardo Mazziotti, Alessandra Mosca, Stefano Frara, Giovanni Vitale, Andrea Giustina
Neuroendocrine tumors (NETs) harbor somatostatin receptors and there is a strong rationale for using somatostatin analogs (SSAs) for treatment of NETs. Areas covered: This article discusses i) pharmacology of somatostatin and its analogs; ii) antisecretory and anti-proliferative effects of SSAs in NETs; iii) efficacy and safety of emerging therapeutic regimens with first generation SSAs administered at either high doses or in combination with antineoplastic drugs; iv) efficacy and safety of pasireotide and chimeric molecules; v) efficacy of radionuclide therapy of NETs using SSAs...
October 25, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29055143/pasireotide-for-the-treatment-of-refractory-hypoglycemia-from-malignant-insulinoma
#7
Nicholas S Hendren, Kamaldeep Panach, Timothy J Brown, Lan Peng, Muhammad S Beg, Jonathan Weissler, Sasan Mirfakhraee
Insulinomas are rare, usually solitary benign tumors. The presence of metastases defines malignant insulinomas((1)) . Medical therapy primarily treats symptomatic hypoglycemia, alleviates symptoms, and improves the quality of life in affected individuals. While diazoxide is used as first-line therapy, the incomplete response rate and complications associated with diazoxide provide a role for somatostatin analogues in difficult-to-treat hypoglycemia. This article is protected by copyright. All rights reserved...
October 21, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/29032486/population-pharmacokinetics-of-subcutaneous-pasireotide-in-healthy-volunteers-and-cushing-s-disease-patients
#8
Jerry Nedelman, Roland Fisch, Ke Hu, Ines Paule, Jocelyn Zhou
BACKGROUND AND OBJECTIVE: Pasireotide (SOM230, Signifor(®)) is a somatostatin analog approved in a subcutaneous formulation for the treatment of Cushing's disease. This analysis characterizes the population pharmacokinetics (PopPK) of subcutaneous pasireotide jointly in healthy volunteers (HVs) and Cushing's disease patients (CDPs), evaluating the effects of age, body size, and population on pasireotide pharmacokinetics. METHODS: The analysis dataset included five phase I studies and one each from phase II and phase III...
October 14, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29032078/efficacy-and-safety-of-once-monthly-pasireotide-in-cushing-s-disease-a-12-month-clinical-trial
#9
André Lacroix, Feng Gu, Wilson Gallardo, Rosario Pivonello, Yerong Yu, Przemysław Witek, Marco Boscaro, Roberto Salvatori, Masanobu Yamada, Libuse Tauchmanova, Michael Roughton, Shoba Ravichandran, Stephan Petersenn, Beverly M K Biller, John Newell-Price
BACKGROUND: Cushing's disease is a rare debilitating endocrine disorder for which few prospective interventional studies have been done. We report results of the first phase 3 trial assessing long-acting intramuscular pasireotide in patients with Cushing's disease. METHODS: In this phase 3 clinical trial we recruited patients aged 18 years or older with persistent, recurrent, or de-novo (non-surgical candidates) Cushing's disease who had a mean urinary free cortisol (mUFC) concentration (from three 24 h samples) of 1·5-5·0 times the upper limit of normal (ULN), a normal or greater than normal morning plasma adrenocorticotropic hormone concentration, and a pituitary source of Cushing's syndrome, from 57 sites across 19 countries...
October 12, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/29026555/pasireotide-and-octreotide-in-the-treatment-of-severe-late-dumping-syndrome
#10
Alireza Mohammadi, Raashda A Sulaiman, Ashley B Grossman
Hypoglycemia due to late dumping is a significant problem postoesophagectomy but may not always be diagnosed sufficiently early. It can be difficult to treat and may severely compromise quality of life. The combination of diazoxide and octreotide or more probably pasireotide may transform the patient's life and should be considered in all problematic cases.
October 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28944744/progress-in-the-formulation-and-delivery-of-somatostatin-analogs-for-acromegaly
#11
Sarinj Fattah, David J Brayden
A 14 amino acid cystin bridge containing neuropeptide was discovered in 1973 and designated as growth hormone-inhibiting hormone, in other words, somatostatin. Its discovery led to the synthesis of three analogs which were licensed for the treatment of acromegaly: octreotide, lanreotide and pasireotide. Somatostatin analogs are currently approved only as either subcutaneous or intramuscular long-acting injections. We examine the challenges that must be overcome to create oral formulations of somatostatin analogs and examine selected clinical trial data...
October 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28903425/pasireotide-is-more-effective-than-octreotide-alone-or-combined-with-everolimus-on-human-meningioma-in-vitro
#12
Thomas Graillon, David Romano, Céline Defilles, Christophe Lisbonis, Alexandru Saveanu, Dominique Figarella-Branger, Pierre-Hugues Roche, Stéphane Fuentes, Olivier Chinot, Henry Dufour, Anne Barlier
Pasireotide is a somatostatin analog (SSA) that targets somatostatin receptor subtype 1 (SST1), SST2, SST3, and SST5 with a high affinity. Pasireotide has a better antisecretory effect in acromegaly, Cushing's disease, and neuroendocrine tumors than octreotide. In this study, we compared the effects of pasireotide to those of octreotide in vitro on meningioma primary cell cultures, both alone and in combination with the mTOR inhibitor everolimus. Significant mRNA expression levels of SST1, SST2, and SST5 were observed in 40...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28835453/aip-and-the-somatostatin-system-in-pituitary-tumours
#13
REVIEW
Alejandro Ibáñez-Costa, Márta Korbonits
Classic somatostatin analogues aimed at somatostatin receptor type 2, such as octreotide and lanreotide, represent the mainstay of medical treatment for acromegaly. These agents have the potential to decrease hormone secretion and reduce tumour size. Patients with a germline mutation in the aryl hydrocarbon receptor-interacting protein gene, AIP, develop young-onset acromegaly, poorly responsive to pharmacological therapy. In this review, we summarise the most recent studies on AIP-related pituitary adenomas, paying special attention to the causes of somatostatin resistance; the somatostatin receptor profile including type 2, type 5 and truncated variants; the role of G proteins in this pathology; the use of first and second generation somatostatin analogues; and the role of ZAC1, a zinc-finger protein with expression linked to AIP in somatotrophinoma models and acting as a key mediator of octreotide response...
December 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28822091/effect-of-ap102-a-subtype-2-and-5-specific-somatostatin-analog-on-glucose-metabolism-in-rats
#14
Erika Tarasco, Petra Seebeck, Svende Pfundstein, Adrian F Daly, Philippe J Eugster, Alan G Harris, Eric Grouzmann, Thomas A Lutz, Christina N Boyle
PURPOSE: Somatostatin analogs are widely used to treat conditions associated with hormonal hypersecretion such as acromegaly and metastatic neuroendocrine tumors. First generation somatostatin analogs, such as octreotide and lanreotide, have high affinity for somatostatin receptor subtype 2 (SSTR2), but have incomplete efficacy in many patients. Pasireotide targets multiple SSTRs, having the highest affinity for SSTR5, but causes hyperglycemia and diabetes mellitus in preclinical and clinical studies...
October 2017: Endocrine
https://www.readbyqxmd.com/read/28762950/pasireotide-is-more-effective-than-octreotide-alone-or-combined-with-everolimus-on-human-meningioma-in-vitro
#15
Thomas Graillon, David Romano, Céline Defilles, Christophe Lisbonis, Alexandru Saveanu, Dominique Figarella-Branger, Pierre-Hugues Roche, Stéphane Fuentes, Olivier Chinot, Henry Dufour, Anne Barlier
Pasireotide is a somatostatin analog (SSA) that targets somatostatin receptor subtype 1 (SST1), SST2, SST3, and SST5 with a high affinity. Pasireotide has a better antisecretory effect in acromegaly, Cushing's disease, and neuroendocrine tumors than octreotide. In this study, we compared the effects of pasireotide to those of octreotide in vitro on meningioma primary cell cultures, both alone and in combination with the mTOR inhibitor everolimus. Significant mRNA expression levels of SST1, SST2, and SST5 were observed in 40...
July 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28741655/treatment-of-a-thyrotropin-secreting-pituitary-adenoma-tsh-oma-with-pasireotide-lar
#16
LETTER
Marlise E A van Eersel, Susanne H Meeuwisse-Pasterkamp, Anneke C Muller Kobold, Linda C Meiners, Wilfred F den Dunnen, Leo J Hofland, Gerrit van den Berg
No abstract text is available yet for this article.
December 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28721221/pasireotide-successful-treatment-of-a-sparsely-granulated-tumour-in-a-resistant-case-of-acromegaly
#17
W K M G Amarawardena, K D Liyanarachchi, J D C Newell-Price, R J M Ross, D Iacovazzo, M Debono
The granulation pattern of somatotroph adenomas is well known to be associated with differing clinical and biochemical characteristics, and it has been shown that sparsely granulated tumours respond poorly to commonly used somatostatin receptor ligands (SRLs). We report a challenging case of acromegaly with a sparsely granulated tumour resistant to multiple modalities of treatment, ultimately achieving biochemical control with pasireotide. A 26-year-old lady presented with classical features of acromegaly, which was confirmed by an oral glucose tolerance test...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28721067/phase-i-dose-escalation-study-of-long-acting-pasireotide-in-patients-with-neuroendocrine-tumors
#18
James C Yao, Jennifer A Chan, Alain C Mita, Madan G Kundu, Karina Hermosillo Reséndiz, Ke Hu, Shoba Ravichandran, Jonathan R Strosberg, Edward M Wolin
This phase I study aimed at determining the maximum tolerated dose (MTD) and characterizing the safety, tolerability, pharmacokinetics (PKs), and efficacy of pasireotide in patients with advanced neuroendocrine tumors (NETs). Patients were enrolled in two phases: dose-escalation phase (to determine the MTD) at a starting dose of 80 mg pasireotide long-acting release (LAR) i.m. followed by a dose-expansion phase (to evaluate safety and prelimi-nary efficacy). Associations between PK/pharmacodynamic parameters and clinical outcomes were evaluated using linear regression analysis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28597198/long-term-treatment-of-cushing-s-disease-with-pasireotide-5-year-results-from-an-open-label-extension-study-of-a-phase-iii-trial
#19
S Petersenn, L R Salgado, J Schopohl, L Portocarrero-Ortiz, G Arnaldi, A Lacroix, C Scaroni, S Ravichandran, A Kandra, B M K Biller
BACKGROUND: Treating hypercortisolism in patients with Cushing's disease after failed surgery often requires chronic medication, underlining the need for therapies with favourable long-term efficacy and safety profiles. METHODS: In a randomised, double-blind study, 162 adult patients with persistent/recurrent or de novo Cushing's disease received pasireotide. Patients with mean urinary free cortisol at/below the upper limit of normal or clinical benefit at month 12 could continue receiving pasireotide during an open-ended, open-label phase, the outcomes of which are described herein...
July 2017: Endocrine
https://www.readbyqxmd.com/read/28592706/efficacy-and-safety-of-long-acting-pasireotide-in-japanese-patients-with-acromegaly-or-pituitary-gigantism-results-from-a-multicenter-open-label-randomized-phase-2-study
#20
Shigeyuki Tahara, Mami Murakami, Tomomi Kaneko, Akira Shimatsu
A multicenter, open-label, phase 2 study was conducted to investigate the efficacy and safety of long-acting pasireotide formulation in Japanese patients with acromegaly or pituitary gigantism. Medically naïve or inadequately controlled patients (on somatostatin analogues or dopamine agonists) were included. Primary end point was the proportion of all patients who achieved biochemical control (mean growth hormone [GH] levels<2.5μg/L and normalized insulin-like growth factor-1 [IGF-1]) at month 3. Thirty-three patients (acromegaly, n=32; pituitary gigantism, n=1) were enrolled and randomized 1:1:1 to receive open-label pasireotide 20mg, 40mg, or 60mg...
July 28, 2017: Endocrine Journal
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