Androgen deprivation
therapy (ADT) is the main treatment approach in advanced
prostate cancer and in recent years has primarily involved the use of
gonadotropin-releasing hormone (
GnRH) agonists. However, despite their efficacy,
GnRH agonists have several drawbacks associated with their mode of action. These include an initial
testosterone surge and
testosterone microsurges on repeat administration.
GnRH antagonists provide an alternative approach to ADT with a more direct mode of action that involves immediate blockade of
GnRH receptors. Antagonists produce a more rapid suppression of
testosterone (and
prostate-specific antigen [PSA]) without a
testosterone surge or microsurges and appear to offer an effective and well tolerated option for the hormonal treatment of
prostate cancer. Comparisons with
GnRH agonists have shown
GnRH antagonists to be at least as effective in achieving and maintaining castrate
testosterone levels in patients with
prostate cancer. Furthermore, with antagonists, the lack of an initial
testosterone surge (which may cause clinical flare) may allow more rapid relief of symptoms related to
prostate cancer, avoid the need for concomitant
antiandrogens to prevent clinical flare (so avoiding any
antiandrogen-associated adverse events) and allow
GnRH antagonist use in patients with high tumour burden and/or acute problems such as
spinal cord compression. Although several antagonists have been investigated, only
degarelix and
abarelix are currently available for clinical use in
prostate cancer. Currently,
degarelix is the most extensively studied and widely available agent in this class.
Degarelix is one of a newer generation of antagonists which, in a comprehensive and ongoing clinical development programme, has been shown to provide rapid, profound and sustained
testosterone suppression without the systemic
allergic reactions associated with earlier antagonists. This review examines the currently available data on
GnRH antagonists in
prostate cancer.