Luteinizing hormone-releasing hormone (LHRH) agonists have been the mainstay of androgen deprivation therapy (ADT) for advanced prostate cancer for over two decades. However, their limitations include a transient initial rise in testosterone, failure to reduce testosterone to castrate levels in some patients, incomplete suppression of follicle-stimulating hormone (FSH), and an increased risk of cardiovascular (CV) events in those with pre-existing CV disease.This article considers whether the LHRH antagonist degarelix offers significant advantages over LHRH agonists.
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Areas covered: This review covers the development and introduction of degarelix, its pharmacodynamic and pharmacokinetic properties, and the efficacy and safety results of Phase II and III clinical studies.
Expert opinion: Degarelix has clear pharmacodynamic advantages over the LHRH agonist leuprolide in terms of almost immediate suppression of testosterone to castrate levels and sustained suppression of FSH levels. It reduces the risk of CV events vs agonists in men with pre-existing CV disease. This finding, which may reflect differential effects on FSH and/or endothelial plaques, requires confirmation in a prospective study; however, it is the view of the author that the differential effects on CV events are real and suggest that men with pre-existing CV disease requiring ADT should preferentially be treated with degarelix.
Expert opinion on drug metabolism & toxicology. 2015 Oct 29 [Epub ahead of print]
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