Literature DB >> 20952020

Cardiovascular safety of degarelix: results from a 12-month, comparative, randomized, open label, parallel group phase III trial in patients with prostate cancer.

Matthew R Smith1, Laurence Klotz, Bo-Eric Persson, Tine Kold Olesen, Arthur A M Wilde.   

Abstract

PURPOSE: We assessed the cardiovascular safety profile of degarelix, a new gonadotropin-releasing hormone antagonist.
MATERIALS AND METHODS: This is the first report to our knowledge on cardiovascular safety data from a completed 1-year randomized controlled trial of leuprolide acetate vs degarelix. Outcomes considered in these analyses included the QT interval by central reading and analysis, and cardiovascular adverse events. On multivariate analyses relationships between selected baseline factors and cardiovascular events were evaluated.
RESULTS: There were no significant differences between treatment groups for mean change in Fridericia's correction of QT during the trial. Markedly abnormal Fridericia's correction of QT values (500 milliseconds or greater) were observed in only a small number of subjects by treatment group, that is 2 (less than 1%) in the pooled degarelix group and 2 (1%) in the leuprolide group. Supraventricular arrhythmias were the most common type of arrhythmias, affecting 2% of subjects in the pooled degarelix group and 4% in the leuprolide group. Other arrhythmias occurred in 1% or less of subjects by treatment group. The most frequently reported cardiac disorder was ischemic heart disease, which occurred in 4% of subjects treated with degarelix and 10% of those on leuprolide. Cox proportional hazard ratio estimates for selected baseline covariates showed a significantly increased risk of cardiovascular events by age (p=0.0459) and systolic blood pressure (p=0.0061).
CONCLUSIONS: In men with prostate cancer degarelix and leuprolide have similar cardiovascular safety profiles. These observations suggest that the cardiovascular events associated with both agents result from hypogonadism rather than a direct drug effect.
Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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Year:  2010        PMID: 20952020      PMCID: PMC3047399          DOI: 10.1016/j.juro.2010.08.012

Source DB:  PubMed          Journal:  J Urol        ISSN: 0022-5347            Impact factor:   7.450


  15 in total

1.  A 1-year, open label, randomized phase II dose finding study of degarelix for the treatment of prostate cancer in North America.

Authors:  Marc Gittelman; Peter J Pommerville; Bo-Eric Persson; Jens-Kristian Jensen; Tine Kold Olesen
Journal:  J Urol       Date:  2008-09-17       Impact factor: 7.450

2.  Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer.

Authors:  Nancy L Keating; A James O'Malley; Matthew R Smith
Journal:  J Clin Oncol       Date:  2006-09-20       Impact factor: 44.544

3.  Sex differences on the electrocardiographic pattern of cardiac repolarization: possible role of testosterone.

Authors:  H Bidoggia; J P Maciel; N Capalozza; S Mosca; E J Blaksley; E Valverde; G Bertran; P Arini; M O Biagetti; R A Quinteiro
Journal:  Am Heart J       Date:  2000-10       Impact factor: 4.749

Review 4.  Androgen-deprivation therapy in prostate cancer and cardiovascular risk: a science advisory from the American Heart Association, American Cancer Society, and American Urological Association: endorsed by the American Society for Radiation Oncology.

Authors:  Glenn N Levine; Anthony V D'Amico; Peter Berger; Peter E Clark; Robert H Eckel; Nancy L Keating; Richard V Milani; Arthur I Sagalowsky; Matthew R Smith; Neil Zakai
Journal:  CA Cancer J Clin       Date:  2010-02-02       Impact factor: 508.702

Review 5.  Androgen deprivation therapy and risk for diabetes and cardiovascular disease in prostate cancer survivors.

Authors:  Matthew R Smith
Journal:  Curr Urol Rep       Date:  2008-05       Impact factor: 3.092

6.  Degarelix: a novel gonadotropin-releasing hormone (GnRH) receptor blocker--results from a 1-yr, multicentre, randomised, phase 2 dosage-finding study in the treatment of prostate cancer.

Authors:  Hendrik Van Poppel; Bertrand Tombal; Jean J de la Rosette; Bo-Eric Persson; Jens-Kristian Jensen; Tine Kold Olesen
Journal:  Eur Urol       Date:  2008-05-08       Impact factor: 20.096

Review 7.  hERG potassium channels and the structural basis of drug-induced arrhythmias.

Authors:  John S Mitcheson
Journal:  Chem Res Toxicol       Date:  2008-05-01       Impact factor: 3.739

8.  The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer.

Authors:  Laurence Klotz; Laurent Boccon-Gibod; Neal D Shore; Cal Andreou; Bo-Eric Persson; Per Cantor; Jens-Kristian Jensen; Tine Kold Olesen; Fritz H Schröder
Journal:  BJU Int       Date:  2008-12       Impact factor: 5.588

Review 9.  Testosterone in obesity, metabolic syndrome and type 2 diabetes.

Authors:  R Stanworth; T Jones
Journal:  Front Horm Res       Date:  2009       Impact factor: 2.606

Review 10.  Increased risk of metabolic syndrome, diabetes mellitus, and cardiovascular disease in men receiving androgen deprivation therapy for prostate cancer.

Authors:  Polly E Kintzel; Sandra L Chase; Lisa M Schultz; Timothy J O'Rourke
Journal:  Pharmacotherapy       Date:  2008-12       Impact factor: 4.705

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  26 in total

1.  ADT and the metabolic syndrome: no good deed goes unpunished.

Authors:  Jehonathan H Pinthus
Journal:  Can Urol Assoc J       Date:  2011-02       Impact factor: 1.862

Review 2.  Degarelix: a review of its use in patients with prostate cancer.

Authors:  Natalie J Carter; Susan J Keam
Journal:  Drugs       Date:  2014-04       Impact factor: 9.546

3.  Gonadotropin-releasing hormone blockers and cardiovascular disease risk: analysis of prospective clinical trials of degarelix.

Authors:  Matthew R Smith; Laurence Klotz; Egbert van der Meulen; Enrico Colli; László B Tankó
Journal:  J Urol       Date:  2011-09-25       Impact factor: 7.450

Review 4.  Adverse effects of androgen deprivation therapy in men with prostate cancer: a focus on metabolic and cardiovascular complications.

Authors:  Lauren Collins; Shehzad Basaria
Journal:  Asian J Androl       Date:  2012-02-20       Impact factor: 3.285

5.  An update on the use of gonadotropin-releasing hormone antagonists in prostate cancer.

Authors:  Laurent Boccon-Gibod; Egbert van der Meulen; Bo-Eric Persson
Journal:  Ther Adv Urol       Date:  2011-06

6.  Evaluation of histopathological findings at the injection site following degarelix administration.

Authors:  Takahiro Maeda; Takeo Kosaka; Aki Honda; Utako Okata; Nozomi Hayakawa; Yujiro Ito; Hirohiko Nagata; Ko-Ron Chen; So Nakamura; Mototsugu Oya
Journal:  Support Care Cancer       Date:  2014-10-31       Impact factor: 3.603

Review 7.  Systemic therapy for the treatment of hormone-sensitive metastatic prostate cancer: from intermittent androgen deprivation therapy to chemotherapy.

Authors:  Bobby C Liaw; Jeffrey Shevach; William K Oh
Journal:  Curr Urol Rep       Date:  2015-03       Impact factor: 3.092

Review 8.  Cancer Chemotherapy-Induced Sinus Bradycardia: A Narrative Review of a Forgotten Adverse Effect of Cardiotoxicity.

Authors:  Juan Tamargo; Ricardo Caballero; Eva Delpón
Journal:  Drug Saf       Date:  2022-01-13       Impact factor: 5.606

9.  Experience with degarelix in the treatment of prostate cancer.

Authors:  Neal D Shore
Journal:  Ther Adv Urol       Date:  2013-02

10.  Medical Castration Using the Investigational Oral GnRH Antagonist TAK-385 (Relugolix): Phase 1 Study in Healthy Males.

Authors:  David B MacLean; Hongliang Shi; Hélène M Faessel; Fred Saad
Journal:  J Clin Endocrinol Metab       Date:  2015-10-26       Impact factor: 5.958

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