Experience with degarelix in the treatment of prostate cancer

Abstract

Degarelix is a gonadotrophin-releasing hormone (GnRH) antagonist for the first-line treatment of androgen-dependent advanced prostate cancer. It has a direct mechanism of action that blocks the action of GnRH on the pituitary with no initial surge in gonadotrophin or testosterone levels. Degarelix is the most extensively studied and widely available GnRH antagonist worldwide. Clinical studies have demonstrated similar efficacy to the GnRH agonist leuprolide in achieving testosterone suppression in patients with prostate cancer. However, degarelix produces a faster suppression of testosterone and prostate-specific antigen (PSA), with no testosterone surge or microsurges, thus preventing the risk of clinical flare in advanced disease. Clinical trials have demonstrated that degarelix can offer improved disease control when compared with a GnRH agonist in terms of superior PSA progression-free survival (suggesting that degarelix likely delays progression to castration-resistant disease), and a more significant impact on bone serum alkaline phosphatase and follicle-stimulating hormone. Degarelix is generally well tolerated, with no reports of systemic allergic reactions in any clinical studies. In conclusion, degarelix offers clinicians a rational first-line hormonal monotherapy option for the management of advanced prostate cancer.

Keywords: GnRH agonist; GnRH antagonist; degarelix; prostate cancer.

Figure 1.

Median serum testosterone levels during the first month of treatment with degarelix versus leuprolide in the phase III CS21 trial. Reprinted from Klotz et al. [2008] with permission from Wiley-Blackwell.

Figure 2.

The mean (standard error of the mean) change in serum alkaline phosphatase levels (normalized to baseline) by (a) baseline disease stage and (b) baseline prostate-specific antigen (PSA) level. Reprinted from Schröder et al. [2010] with permission from Wiley-Blackwell.

Figure 3.

Prostate-specific antigen (PSA) progression-free survival (PFS) probability in the phase III extension study CS21A (all patients). Reprinted from Crawford et al. [2011] with permission from Elsevier.

Figure 4.

Median percentage change from baseline and quartiles in follicle-stimulating hormone in patients switched from leuprolide to degarelix and those continuing degarelix in the extension trial. Reprinted from Crawford et al. [2011] with permission from Elsevier.