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Pasireotide

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https://www.readbyqxmd.com/read/29643113/pasireotide-in-the-treatment-of-neuroendocrine-tumors-a-review-of-the-literature
#1
Giovanni Vitale, Alessandra Dicitore, Concetta Sciammarella, Sergio Di Molfetta, Manila Rubino, Antongiulio Faggiano, Annamaria A L Colao
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...
April 11, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29621813/cushing-s-syndrome-a-historic-review-of-the-treatment-strategies-and-corresponding-outcomes-in-a-single-tertiary-center-over-the-past-half-century
#2
Anelia Nankova, Maria Yaneva, Atanaska Elenkova, Dimitar Tcharaktchiev, Marin Marinov, Asen Hadzhiyanev, Tanyo Sechanov, Georgi Gantchev, Georgi Todorov, Georgi Kirilov, Krasimir Kalinov, Maria Andreeva, Sabina Zacharieva
Cushing's syndrome (CS) is associated with serious comorbidities and an increased mortality rate that could be reduced only if strict biochemical control is achieved. The aim of this study was to show the 50-year experience of a single tertiary center in the management of CS patients - the different treatment modalities used over the years and the corresponding outcomes. It was a retrospective study of a large cohort of patients from the Bulgarian CS database: 613 patients (374 with ACTH-dependent and 239 with ACTH-independent CS)...
April 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29595102/pasireotide-mechanism-of-action-and-clinical-applications
#3
Nadia Sawicka-Gutaj, Maciej Owecki, Marek Ruchala
Pasireotide (SOM230) is a multi-receptor ligand somatostatin analogue (SSA) developed as the successor of the first-generation SSAs. Currently, pasireotide is recommended for the treatment of patients with Cushing's disease in whom surgery was unsuccessful, and patients with acromegaly who either remain uncontrolled after surgical therapy or in whom tumor resection is not possible. Phase II and III clinical trials have shown pasireotide efficacy in these diseases, with a similar rate of adverse events when compared with first-line SSA, although higher incidence of hyperglycemia has been observed...
March 27, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29572709/the-antiproliferative-effect-of-pasireotide-lar-alone-and-in-combination-with-everolimus-in-patients-with-medullary-thyroid-cancer-a-single-center-open-label-phase-ii-proof-of-concept-study
#4
Antongiulio Faggiano, Roberta Modica, Rosa Severino, Luigi Camera, Rosa Fonti, Michela Del Prete, Maria Grazia Chiofalo, Massimo Aria, Piero Ferolla, Giovanni Vitale, Luciano Pezzullo, Annamaria Colao
PURPOSE: Medullary thyroid cancer (MTC) is a neuroendocrine tumour of the thyroid C cells. Pasireotide, a multi-receptor targeted somatostatin analogue, and everolimus, an inhibitor of mTOR, showed antitumour properties in neuroendocrine tumours. Aim of this study was to evaluate pasireotide alone and in combination with everolimus in patients with MTC. METHODS: Patients with progressive metastatic or persistent postoperative MTC received pasireotide LAR 60 mg/m for at least 6 months...
March 23, 2018: Endocrine
https://www.readbyqxmd.com/read/29563895/novel-somatostatin-receptor-ligands-therapies-for-acromegaly
#5
REVIEW
Rosa Maria Paragliola, Roberto Salvatori
Surgery is considered the treatment of choice in acromegaly, but patients with persistent disease after surgery or in whom surgery cannot be considered require medical therapy. Somatostatin receptor ligands (SRLs) octreotide (OCT), lanreotide, and the more recently approved pasireotide, characterized by a broader receptor ligand binding profile, are considered the mainstay in the medical management of acromegaly. However, in the attempt to offer a more efficacious and better tolerated medical approach, recent research has been aimed to override some limitations related to the use of currently approved drugs and novel SRLs therapies, with potential attractive features, have been proposed...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29534939/phase-i-trial-of-the-combination-of-docetaxel-prednisone-and-pasireotide-in-metastatic-castrate-resistant-prostate-cancer
#6
Manish K Thakur, Lance Heilbrun, Kimberlee Dobson, Julie Boerner, Karri Stark, Jing Li, Daryn Smith, Elisabeth Heath, Joseph Fontana, Ulka Vaishampayan
BACKGROUND: Pasireotide (SOM230; Novartis Inc, Basel, Switzerland) is a multitargeted somatostatin receptor analogue likely to treat the neuroendocrine, and docetaxel resistant components within metastatic castrate-resistant prostate cancer (mCRPC). This phase I trial tested the combination of pasireotide, docetaxel, and prednisone in pretreated mCRPC. PATIENTS AND METHODS: Chemotherapy naive mCRPC patients received docetaxel 75 mg/m2 intravenously every 21 days and pasireotide intramuscularly every 28 days at escalating dose levels of 40, 60, and 80 mg...
February 13, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29523357/cellular-effects-of-ap102-a-somatostatin-analog-with-balanced-affinities-for-the-hsstr2-and-hsstr5-receptors
#7
Jeremy Streuli, Alan G Harris, Cecilia Cottiny, Florent Allagnat, Adrian F Daly, Eric Grouzmann, Karim Abid
BACKGROUND: Somatostatin analogs (SSAs) are first-line medical therapy for the treatment of acromegaly and neuroendocrine tumors that express somatostatin receptors (SSTR). Somatostatin suppresses secretion of a large number of hormones through the stimulation of the five SSTR. However, unbalanced inhibition of secretion as observed with the highly potent SSAs pasireotide causes hyperglycaemia mainly by inhibiting insulin secretion. In contrast, AP102 a new SSAs has neutral effect on blood glucose while suppressing GH secretion...
March 2, 2018: Neuropeptides
https://www.readbyqxmd.com/read/29479375/efficacy-and-safety-of-pasireotide-lar-for-the-treatment-of-refractory-bleeding-due-to-gastrointestinal-angiodysplasias-results-of-the-angiopas-multicenter-phase-ii-noncomparative-prospective-double-blinded-randomized-study
#8
Robert Benamouzig, Mourad Benallaoua, Jean-Christophe Saurin, Marouane Boubaya, Christophe Cellier, René Laugier, Magalie Vincent, Christian Boustière, Rodica Gincul, Elia Samaha, Philippe Grandval, Thomas Aparicio, Gheorghe Airinei, Bakhtiar Bejou, Cyriaque Bon, Jean-Jacques Raynaud, Vincent Levy, Denis Sautereau
Background: Gastrointestinal angiodysplasias (GIADs) could be responsible for recurrent bleeding and severe anemia. Somatostatin analogs could reduce transfusion requirements in these patients but no randomized controlled study is available. The main objective of the ANGIOPAS phase II double-blinded randomized, noncomparative study was to assess the effectiveness of pasireotide-LAR in reducing transfusion requirements in patients with refractory GIADs bleeding. Methods: A total of 22 patients with transfusion requirements ⩾6 units of packed red blood cells (pRBCs) during the 6 months prior to inclusion were randomized to receive pasireotide-LAR 60 mg ( n = 10) or placebo ( n = 12) every 28 days for 6 months...
2018: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29451701/phase-1b-study-of-pasireotide-everolimus-and-selective-internal-radioembolization-therapy-for-unresectable-neuroendocrine-tumors-with-hepatic-metastases
#9
Hyun S Kim, Walid L Shaib, Chao Zhang, Ganji Purnachandra Nagaraju, Christina Wu, Olatunji B Alese, Zhengjia Chen, Edith Brutcher, Meredith Renfroe, Bassel F El-Rayes
BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2...
February 16, 2018: Cancer
https://www.readbyqxmd.com/read/29398424/pasireotide-does-not-prevent-postoperative-pancreatic-fistula-a-prospective-study
#10
Irmina A Elliott, Amanda M Dann, Razmik Ghukasyan, Lauren Damato, Mark D Girgis, Jonathan C King, O J Hines, Howard A Reber, Timothy R Donahue
BACKGROUND: Pancreatic fistula is a major cause of morbidity after pancreas surgery. In 2014, a single-center, randomized-controlled trial found pasireotide decreased pancreatic fistula rates. However, this finding has not been validated, nor has pasireotide been widely adopted. METHODS: A single-arm study in 111 consecutive patients undergoing pancreatic resection April 2015-October 2016 was conducted. Beginning immediately before surgery, patients received 900 μg subcutaneous pasireotide twice daily for up to seven days...
February 2, 2018: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/29396758/insulin-sensitivity-and-secretion-and-adipokine-profile-in-patients-with-cushing-s-disease-treated-with-pasireotide
#11
V Guarnotta, G Pizzolanti, A Ciresi, C Giordano
PURPOSE: To evaluate the effect of pasireotide on β-cell and adipose function in patients with Cushing's disease (CD). METHODS: Clinical and hormonal parameters, insulin secretion evaluated by HOMA-β and by the area under the curve (AUC2h) of C-peptide during a mixed meal tolerance test and insulin sensitivity, evaluated by the euglycaemic hyperinsulinaemic clamp, were evaluated in 12 patients with active CD, before and after 6 and 12 months of pasireotide. In addition, a panel of adipokines including leptin (Ob), leptin/leptin receptor ratio (Ob/Ob-R ratio), adiponectin, resistin, visfatin, adipocyte fatty acid binding protein (AFABP) and non-esterified fatty acids (NEFAs) was evaluated at baseline and after 12 months of pasireotide...
February 2, 2018: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29392123/phase-ii-trial-of-som230-pasireotide-lar-in-patients-with-unresectable-hepatocellular-carcinoma
#12
Lynn G Feun, Medhi Wangpaichitr, Ying-Ying Li, Deukwoo Kwon, Stephen P Richman, Peter J Hosein, Niramol Savaraj
Background: A phase II trial of pasireotide was performed to assess its efficacy and safety in advanced or metastatic hepatocellular carcinoma (HCC). Patients and methods: Patients with advanced HCC and Child-Pugh score ≤7 received pasireotide LAR 60 mg intramuscularly every 28 days. Primary endpoint was disease control rate. Secondary endpoints were time to tumor progression, response rate, treatment-related adverse events, and overall survival. Serum insulin growth factor-1 was measured before and after pasireotide...
2018: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/29383677/pasireotide-treatment-reduces-cardiometabolic-risk-in-cushing-s-disease-patients-an-italian-multicenter-study
#13
A Albani, F Ferraù, A Ciresi, R Pivonello, C Scaroni, D Iacuaniello, M Zilio, V Guarnotta, A Alibrandi, E Messina, M Boscaro, C Giordano, A Colao, S Cannavo
PURPOSE: Patients with Cushing's disease (CD) experience metabolic alterations leading to increased cardiovascular mortality. Recently, the visceral adiposity index (VAI) has been proposed as a marker of visceral adipose tissue dysfunction (ATD) and of the related cardiometabolic risk. We aimed to evaluate the impact of 12-month pasireotide treatment on cardiometabolic risk in CD patients. METHODS: This is a multicentre, prospective, and observational study. Sixteen CD patients, referred to the Endocrine Units of the University Hospitals of Messina, Napoli, Padova, and Palermo (Italy), successfully treated with pasireotide for 12 month have been enrolled...
January 30, 2018: Endocrine
https://www.readbyqxmd.com/read/29371000/pasireotide-in-acromegaly-by-aggressive-tumors-description-of-four-clinical-cases-towards-a-personalized-medicine
#14
Betina Biagetti, Gabriel Obiols, Elena Martinez Saez, Esteban Cordero, Jordi Mesa
No abstract text is available yet for this article.
January 19, 2018: Endocrinología, Diabetes y Nutrición
https://www.readbyqxmd.com/read/29366679/combination-of-a-histone-deacetylase-6-inhibitor-and-a-somatostatin-receptor-agonist-synergistically-reduces-hepatorenal-cystogenesis-in-an-animal-model-of-polycystic-liver-disease
#15
Maria Lorenzo Pisarello, Tatyana V Masyuk, Sergio A Gradilone, Anatoliy I Masyuk, Jingyi Francess Ding, Pui-Yuen Lee, Nicholas F LaRusso
Hepatic cystogenesis in polycystic liver disease (PLD) is associated with abnormalities in multiple cellular processes, including elevated cAMP and overexpression of histone deacetylase 6 (HDAC6). Disease progression in polycystic kidney (PCK) rats (an animal model of PLD) is attenuated by inhibition of either cAMP production or HDAC6. Therefore, we hypothesized that concurrent targeting of HDAC6 and cAMP would synergistically reduce cyst growth. Changes in hepatorenal cystogenesis were examined in PCK rats treated with a pan-HDAC inhibitor, panobinostat; three specific HDAC6 inhibitors, ACY-1215, ACY-738, and ACY-241; and a combination of ACY-1215 and the somatostatin receptor analogue, pasireotide...
January 31, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29361932/efficacy-of-combined-treatment-with-pasireotide-pegvisomant-and-cabergoline-in-an-acromegalic-patient-resistant-to-other-treatments-a-case-report
#16
A Ciresi, S Radellini, V Guarnotta, C Giordano
BACKGROUND: The approach to acromegalic patients with persistent acromegaly after surgery and inadequate response to first-generation somatostatin receptor ligands (SRLs) should be strictly tailored. Current options include new pituitary surgery and/or radiosurgery, or alternative medical treatment with SRLs high dose regimens, pegvisomant (PEG) as monotherapy, or combined therapy with the addition of PEG or cabergoline to SRLs. A new pharmacological approach includes pasireotide, a second-generation SRL approved for patients who do not adequately respond to surgery and/or for whom surgery is not an option...
January 24, 2018: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/29357081/biochemical-efficacy-of-long-acting-lanreotide-depot-autogel-in-patients-with-acromegaly-na%C3%A3-ve-to-somatostatin-receptor-ligands-analysis-of-three-multicenter-clinical-trials
#17
Hussain Alquraini, Maria Del Pilar Schneider, Beloo Mirakhur, Ariel Barkan
PURPOSE: In clinical research involving acromegalic patients naïve to somatostatin-receptor ligands (SRLs), 19 and 31% of those receiving the SRLs octreotide LAR and pasireotide LAR, respectively, achieved GH < 2.5 ng/mL + normalized IGF-1 concentrations. The proportions achieving control appeared higher in the post-surgery compared with the de-novo setting with pasireotide, but more similar with octreotide. Using pooled data from multicenter clinical trials, we examined the biochemical efficacy of lanreotide depot/Autogel in similar settings...
January 22, 2018: Pituitary
https://www.readbyqxmd.com/read/29318424/pasireotide-does-not-improve-efficacy-of-aspiration-sclerotherapy-in-patients-with-large-hepatic-cysts-a-randomized-controlled-trial
#18
Titus F M Wijnands, Tom J G Gevers, Marten A Lantinga, René H Te Morsche, Leo J Schultze Kool, Joost P H Drenth
OBJECTIVES: We tested whether complementary use of the somatostatin analogue pasireotide would augment efficacy of aspiration sclerotherapy of hepatic cysts. METHODS: We conducted a double-blind, placebo-controlled trial in patients who underwent aspiration sclerotherapy of a large (>5 cm) symptomatic hepatic cyst. Patients were randomized to either intramuscular injections of pasireotide 60 mg long-acting release (n = 17) or placebo (sodium chloride 0.9 %, n = 17)...
January 9, 2018: European Radiology
https://www.readbyqxmd.com/read/29313180/a-prospective-longitudinal-study-of-pasireotide-in-nelson-s-syndrome
#19
Eleni Daniel, Miguel Debono, Sharon Caunt, Constantine Girio-Fragkoulakis, Stephen J Walters, Scott A Akker, Ashley B Grossman, Peter J Trainer, John Newell-Price
PURPOSE: Nelson's syndrome is a challenging condition that can develop following bilateral adrenalectomy for Cushing's disease, with high circulating ACTH levels, pigmentation and an invasive pituitary tumor. There is no established medical therapy. The aim of the study was to assess the effects of pasireotide on plasma ACTH and tumor volume in Nelson's syndrome. METHODS: Open labeled multicenter longitudinal trial in three steps: (1) a placebo-controlled acute response test; (2) 1 month pasireotide 300-600 μg s...
January 8, 2018: Pituitary
https://www.readbyqxmd.com/read/29226331/a-novel-pathway-activated-by-somatostatin-receptor-type-2-sst2-inhibition-of-pituitary-tumor-cell-migration-and-invasion-through-cytoskeleton-protein-recruitment
#20
E Peverelli, E Giardino, D Treppiedi, R Catalano, F Mangili, M Locatelli, A G Lania, M Arosio, A Spada, G Mantovani
The pharmacological therapy of GH-secreting pituitary tumors is based on somatostatin (SS) analogs that reduce GH secretion and cell proliferation by binding mainly SS receptors type 2 (SST2). Antimigratory effects of SS have been demonstrated in different cell models, but no data on pituitary tumors are available. Aims of our study were to evaluate SST2 effects on migration and invasion of human and rat tumoral somatotrophs, and to elucidate the molecular mechanism involved focusing on the role of cofilin and filamin A (FLNA)...
May 1, 2018: International Journal of Cancer. Journal International du Cancer
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