R E V I E W Degarelix and its therapeutic potential in the treatment of prostate cancer Christian Doehn Martin Sommerauer Dieter Jocham Department of Urology, University of Lübeck Medical School, Lübeck, Germany Correspondence: Christian Doehn Department of Urology, University of Lübeck Medical School, Ratzeburger Allee 160, 23538 Lübeck, Germany Tel +49 451 500 6113 Fax +49 451 500 4666 Email doehn@medinf.mu-luebeck.de Abstract: Degarelix is a gonadotropin-releasing hormone (GnRH) antagonist for the treatment of patients with prostate cancer in whom hormonal therapy is indicated. Two phase II trials and one phase III have been published as full papers in the literature. In the dose-ﬁnding phase II studies an initial dose of 240 mg degarelix sc followed by a monthly injection of 80 mg or 160 mg degarelix sc was sufﬁcient to keep testosterone levels 0.5 ng/ml. In a phase III trial it was demonstrated that degarelix was not inferior (in terms of testosterone suppression and prostate-speciﬁc antigen [PSA] decline) compared to standard hormonal therapy, ie, a GnRH agonist such as leuprolide. In fact, degarelix was associated with a faster testosterone suppression and PSA decline than leuprolide. Adverse events such as injection site reactions (40% vs 1%) and chills (4% vs 0%) were more commonly associated with degarelix. Also, degarelix is currently only available as one-month depot whereas in daily practice three-month depots (of GnRH agonists) are the preferred regimen. However, degarelix was recently approved by the US Food and Drug Administration for the treatment of advanced prostate cancer. Keywords: prostate cancer, hormonal therapy, GnRH antagonist, degarelix, testosterone, ﬂare Introduction Prostate cancer is the most common malignancy in the US and in western Europe with an estimated 186,320 newly diagnosed cases in 2008 in the US and 28,660 men who died of prostate cancer in the US (incidence-mortality ratio of 6.5).1 The therapeutic options available predominantly depend on cancer stage as well as patient age and co-morbidity. In organ-conﬁned prostate cancer the treatment is radical prostatectomy, external beam radiotherapy, or brachytherapy. In this stage of the disease, therapy is with curative intention and patients have an excellent prognosis.2 Active surveillance or watchful waiting are also options in patients with low risk organ-conﬁned prostate cancer (ie, clinical stage T1c-2a and Gleason score 6 and prostate-speciﬁc antigen (PSA) less than 10 and less than 33% of prostate biopsies positive for cancer).3 Primary androgen deprivation therapy might also be an option but without curative intention.4 However, androgen deprivation therapy is not regarded as standard in patients with localized prostate cancer.5 In metastatic prostate cancer and/or in patients who are not able to undergo the above treatment options because of their age and/or co-morbidity, the standard of care is androgen deprivation therapy.6 Watchful waiting may also be applied under the latter circumstances. Huggins ﬁrst described the effect of castration on prostate cancer in 1941.7 This was the basis for the ﬁnding that prostate cancer cells need androgens for their growth. Without the receptor-mediated stimulus of androgens prostate cancer cells undergo apoptosis.8,9 Androgens are synthesized in the testes (95%) and in the adrenal glands (5%). The androgen synthesis underlies a hormonal regulation by the hypothalamic– pituitary–gonadal axis in a negative feedback manner. Clinical Interventions in Aging 2009:4 215–223 © 2009 Doehn et al, publisher and licensee Dove Medical Press Ltd.This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. 215