The role of gonadotrophin-releasing hormone antagonists in the treatment of patients with advanced hormone-dependent prostate cancer in the UK.
OBJECTIVE
Comparing gonadotrophin-releasing hormone (GnRH) antagonists and agonists as androgen deprivation therapy for advanced prostate cancer (PC).


METHODS
This article stems from a round-table meeting in December 2014 to compare the properties of GnRH agonists and antagonists in the published literature in order to identify the patient groups most likely to benefit from GnRH antagonist therapy. A broad PubMed and congress abstract search was carried out in preparation for the meeting to ensure that the latest data and opinion were available for the discussions.


RESULTS
In randomised, controlled trials, GnRH antagonist therapy provides more rapid suppression of luteinising hormone, follicle-stimulating hormone and testosterone than GnRH agonist treatment. Compared with the GnRH agonist, there is evidence of improved disease control by a GnRH antagonist, with longer interval to prostate-specific antigen progression and greater reduction of serum alkaline phosphatase. In a post hoc analysis of six randomised trials, the risk of cardiac events within 1 year of initiating therapy was significantly lower among men receiving GnRH antagonist than agonist. Pre-clinical laboratory data suggest a number of mechanisms whereby GnRH antagonist therapy may benefit men with pre-existing cardiovascular disease (CVD), the most plausible hypothesis being that, unlike GnRH agonists, GnRH antagonists do not activate T lymphocytes, which act to increase atherosclerotic plaque rupture.


CONCLUSIONS
When making treatment decisions, clinicians should consider comorbidities, particularly CVD, in addition to effects on PC. GnRH antagonists may be appropriate in patients with significant CV risk, existing osteopenia, lower urinary tract symptoms and significant metastatic disease.
Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK. d.j.rosario@sheffield.ac.uk.
Derek J
DJ
Rosario
Northampton General Hospital, Northampton, UK.
Patrick
P
Davey
Barts Health Hospitals, London, UK.
James
J
Green
Sunderland Royal Hospital, Sunderland, UK.
Damien
D
Greene
Barts Health Hospitals, London, UK.|Homerton University Hospital, London, UK.
Bruce
B
Turner
University College Hospital, London, UK.
Heather
H
Payne
University of Hertfordshire, Hatfield, UK.
Mike
M
Kirby
D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009017:Morbidity; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000453:epidemiology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology
D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone
ADT; Cardiovascular; Degarelix; GnRH; Prostate cancer; UK