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Telotristat

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https://www.readbyqxmd.com/read/27817224/telotristat-ethyl-a-new-option-for-the-management-of-carcinoid-syndrome
#1
Angela Lamarca, Jorge Barriuso, Mairéad G McNamara, Richard A Hubner, Juan W Valle
Many patients with neuroendocrine tumour-related carcinoid syndrome treated with somatostatin analogues (SSA) won't achieve adequate symptom relief with the SSA alone; new treatment options are required. Telotristat ethyl is a tryptophan hydroxylase inhibitor, developed for the treatment of carcinoid syndrome. Areas covered: This review summarises the evidence supporting the role of telotristat ethyl in the management of carcinoid syndrome. Rationale, pharmacodynamics, pharmacokinetics, metabolism, clinical experience, efficacy and toxicity profiles are covered...
November 16, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27635672/treatment-of-symptomatic-neuroendocrine-tumor-syndromes-recent-advances-and-controversies
#2
Tetsuhide Ito, Lingaku Lee, Robert T Jensen
INTRODUCTION: Neuroendocrine tumors(NETs), once thought rare, are increasing in frequency in most countries and receiving increasing-attention. NETs present two-treatment problems. A proportion is aggressive and a proportion has a functional, hormone-excess-state(F-NET) each of which, must be treated. Recently, there have been many advances, well-covered in reviews/consensus papers on imaging-NETs; new, novel anti-tumor treatments and understanding their pathogenesis. However, little attention has been paid to advances in the treatment of the hormone-excess-state...
September 16, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27444653/serotonin-biosynthesis-as-a-predictive-marker-of-serotonin-pharmacodynamics-and-disease-induced-dysregulation
#3
Richard W D Welford, Magali Vercauteren, Annette Trébaul, Christophe Cattaneo, Doriane Eckert, Marco Garzotti, Patrick Sieber, Jérôme Segrestaa, Rolf Studer, Peter M A Groenen, Oliver Nayler
The biogenic amine serotonin (5-HT) is a multi-faceted hormone that is synthesized from dietary tryptophan with the rate limiting step being catalyzed by the enzyme tryptophan hydroxylase (TPH). The therapeutic potential of peripheral 5-HT synthesis inhibitors has been demonstrated in a number of clinical and pre-clinical studies in diseases including carcinoid syndrome, lung fibrosis, ulcerative colitis and obesity. Due to the long half-life of 5-HT in blood and lung, changes in steady-state levels are slow to manifest themselves...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27236421/diagnosis-and-management-of-gastrointestinal-neuroendocrine-tumors-an-evidence-based-canadian-consensus
#4
REVIEW
Simron Singh, Sylvia L Asa, Chris Dey, Hagen Kennecke, David Laidley, Calvin Law, Timothy Asmis, David Chan, Shereen Ezzat, Rachel Goodwin, Ozgur Mete, Janice Pasieka, Juan Rivera, Ralph Wong, Eva Segelov, Daniel Rayson
The majority of neuroendocrine tumors originate in the digestive system and incidence is increasing within Canada and globally. Due to rapidly evolving evidence related to diagnosis and clinical management, updated guidance on the diagnosis and treatment of gastrointestinal neuroendocrine tumors (GI-NETs) are of clinical importance. Well-differentiated GI-NETs may exhibit indolent clinical behavior and are often metastatic at diagnosis. Some NET patients will develop secretory disease requiring symptom control to optimize quality of life and clinical outcomes...
June 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27138571/will-clinical-heterogeneity-of-neuroendocrine-tumors-impact-their-management-in-the-future-lessons-from-recent-trials
#5
Mauro Cives, Heloisa P Soares, Jonathan Strosberg
PURPOSE OF REVIEW: Neuroendocrine tumors (NETs) are a group of biologically and clinically heterogeneous neoplasms arising from the diffuse neuroendocrine system. In the last few years, advances in our understanding of the biology of these tumors have translated into an expansion of treatment options for patients with NETs. Current treatment modalities include somatostatin analogs (SSAs), radiolabeled SSAs, targeted agents, cytotoxic drugs and liver-directed therapies for the management of metastatic disease...
July 2016: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27107003/inhibition-of-peripheral-synthesis-of-serotonin-as-a-new-target-in-neuroendocrine-tumors
#6
REVIEW
Javier Molina-Cerrillo, Teresa Alonso-Gordoa, Olga Martínez-Sáez, Enrique Grande
UNLABELLED: : The carcinoid syndrome represents a set of signs and symptoms associated with neuroendocrine tumors (NETs) that occur primarily when metastases are developed in the liver, resulting in the worsening of quality of life. Serotonin plays a central role in the physiology of carcinoid syndrome by promoting intestinal motility. Somatostatin analogs (SSAs) have widely demonstrated their efficacy as symptomatic relievers of carcinoid syndrome, but this control is ephemeral, being reduced by approximately 50% within the first year...
June 2016: Oncologist
https://www.readbyqxmd.com/read/27041406/patient-reported-symptom-experiences-in-patients-with-carcinoid-syndrome-after-participation-in-a-study-of-telotristat-etiprate-a-qualitative-interview-approach
#7
Heather L Gelhorn, Matthew H Kulke, Thomas O'Dorisio, Qi M Yang, Jessica Jackson, Shanna Jackson, Kristi A Boehm, Linda Law, Jacqueline Kostelec, Priscilla Auguste, Pablo Lapuerta
PURPOSE: Telotristat etiprate, a tryptophan hydroxylase inhibitor, was previously evaluated in a Phase II randomized, placebo-controlled clinical trial in patients with carcinoid syndrome (CS) and diarrhea not adequately controlled by octreotide. The objective of the current study was to characterize the symptom experiences of patients participating in that trial. METHODS: Consenting patients participated in one-on-one, qualitative interviews focused on eliciting symptoms they had experienced in association with their CS diagnosis and recollection of symptom changes they experienced while participating in the Phase II trial...
April 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/26303703/clinical-syndromes-related-to-gastrointestinal-neuroendocrine-neoplasms
#8
REVIEW
Georgios Boutzios, Gregory Kaltsas
Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of tumors derived from multipotent neuroendocrine cells that have the inherent ability to synthesize and secrete a variety of substances (peptides and amines). When these substances are bioactive, NENs can present with a related clinical syndrome (functioning NENs) and/or symptoms of mass effects (functioning and nonfunctioning NENs). NENs differ in their pathogenesis, clinical syndromes produced, aspects of biological behavior and response to certain antitumor treatment...
2015: Frontiers of Hormone Research
https://www.readbyqxmd.com/read/26206858/blocking-peripheral-serotonin-synthesis-by-telotristat-etiprate-lx1032-lx1606-reduces-severity-of-both-chemical-and-infection-induced-intestinal-inflammation
#9
Janice J Kim, Huaqing Wang, Joshua D Terc, Brian Zambrowicz, Qi M Yang, Waliul I Khan
Mucosal inflammation is accompanied by an alteration in 5-HT. Intestinal 5-HT synthesis is catalyzed by tryptophan hydroxylase 1 (Tph1) and we have shown that mice deficient in this rate-limiting enzyme have reduced severity of intestinal inflammation in models of chemical-induced experimental colitis. Here, we investigated the effect of blocking peripheral 5-HT synthesis in generation of intestinal inflammation by a using peripheral Tph inhibitor, telotristat etiprate (LX1606), in models of intestinal inflammation...
September 15, 2015: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/25636046/telotristat-etiprate-for-carcinoid-syndrome-a-single-arm-multicenter-trial
#10
MULTICENTER STUDY
Marianne Pavel, Dieter Hörsch, Martyn Caplin, John Ramage, Thomas Seufferlein, Juan Valle, Phillip Banks, Pablo Lapuerta, Arthur Sands, Brian Zambrowicz, Douglas Fleming, Bertram Wiedenmann
CONTEXT: Carcinoid syndrome (CS) is associated with elevated serotonin, diarrhea, flushing, and increased risk of valvular heart disease. Many patients respond to somatostatin analogs initially, but response diminishes in most patients. Additional options are needed. OBJECTIVE: To assess whether telotristat etiprate (TE) can reduce gastrointestinal symptoms in CS and reduce urinary 5-hydroxyindoleacetic acid (u5-HIAA; a biomarker of serotonin). DESIGN: A prospective, exploratory, dose-escalating 12-week, open-label, multicenter study of TE with efficacy and safety analyses...
April 2015: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/25012985/telotristat-etiprate-a-novel-serotonin-synthesis-inhibitor-in-patients-with-carcinoid-syndrome-and-diarrhea-not-adequately-controlled-by-octreotide
#11
RANDOMIZED CONTROLLED TRIAL
Matthew H Kulke, Thomas O'Dorisio, Alexandria Phan, Emily Bergsland, Linda Law, Phillip Banks, Joel Freiman, Kenny Frazier, Jessica Jackson, James C Yao, Larry Kvols, Pablo Lapuerta, Brian Zambrowicz, Douglas Fleming, Arthur Sands
Serotonin produced by neuroendocrine tumors is believed to be a principal cause of the diarrhea in carcinoid syndrome. We assessed the safety and efficacy of telotristat etiprate, an oral serotonin synthesis inhibitor, in patients with diarrhea associated with carcinoid syndrome. In this prospective, randomized study, patients with evidence of carcinoid tumor and ≥4 bowel movements (BMs)/day despite stable-dose octreotide LAR depot therapy were enrolled in sequential, escalating, cohorts of four patients per cohort...
October 2014: Endocrine-related Cancer
https://www.readbyqxmd.com/read/23749550/pharmacological-reduction-of-mucosal-but-not-neuronal-serotonin-opposes-inflammation-in-mouse-intestine
#12
Kara Gross Margolis, Korey Stevanovic, Zhishan Li, Qi Melissa Yang, Tamas Oravecz, Brian Zambrowicz, Kanchan G Jhaver, Alexander Diacou, Michael D Gershon
OBJECTIVE: Enterochromaffin cell-derived serotonin (5-HT) promotes intestinal inflammation. We tested hypotheses that peripheral tryptophan hydroxylase (TPH) inhibitors, administered orally, block 5-HT biosynthesis and deplete 5-HT from enterochromaffin cells sufficiently to ameliorate intestinal inflammation; moreover, peripheral TPH inhibitors fail to enter the murine enteric nervous system (ENS) or central nervous systems and thus do not affect constitutive gastrointestinal motility...
June 2014: Gut
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