PD37-04 A PHASE II, RANDOMIZED, OPEN LABEL STUDY OF NEOADJUVANT DEGARELIX VERSUS LHRH AGONIST IN PROSTATE CANCER PATIENTS PRIOR TO RADICAL PROSTATECTOMY (2016)

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy IV1 Apr 2016PD37-04 A PHASE II, RANDOMIZED, OPEN LABEL STUDY OF NEOADJUVANT DEGARELIX VERSUS LHRH AGONIST IN PROSTATE CANCER PATIENTS PRIOR TO RADICAL PROSTATECTOMY Rashid Sayyid, Martin Gleave, Karen Hersey, Ranjena Maloni, Antonio Hurtado-Coll, Andrew Evans, Girish Kulkarni, Antonio Finelli, Alexandre Zlotta, Robert Hamilton, Michael Jewett, and Neil Fleshner Rashid SayyidRashid Sayyid More articles by this author , Martin GleaveMartin Gleave More articles by this author , Karen HerseyKaren Hersey More articles by this author , Ranjena MaloniRanjena Maloni More articles by this author , Antonio Hurtado-CollAntonio Hurtado-Coll More articles by this author , Andrew EvansAndrew Evans More articles by this author , Girish KulkarniGirish Kulkarni More articles by this author , Antonio FinelliAntonio Finelli More articles by this author , Alexandre ZlottaAlexandre Zlotta More articles by this author , Robert HamiltonRobert Hamilton More articles by this author , Michael JewettMichael Jewett More articles by this author , and Neil FleshnerNeil Fleshner More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1143AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Androgen deprivation therapy is considered standard systemic treatment for advanced prostate cancer. There is renewed interest in exploring neo-adjuvant strategies prior to radical prostatectomy. Degarelix, a new GnRH receptor antagonist with demonstrated efficacy as a first-line treatment in the management of high-risk prostate cancer, possesses some theoretical advantages over LHRH analogues in terms of avoiding ″testosterone flare″ and lower FSH levels. We set out to determine if pre-operative Degarelix influenced surrogates of disease control in a randomized phase II study. METHODS 39 patients were assigned randomly to one of 3 different neo-adjuvant arms: Degarelix (Arm A), Degarelix and bicalutmaide (Arm B), or LHRH agonist and bicalutamide (Arm C). All study participants received their treatments for 3 months prior to radical prostatectomy. The population consisted of patients with localized prostate cancer who chose radical prostatectomy as primary treatment. Eligibility was limited to those with a Gleason Score ≥7 and/or clinical stage ≥T2 disease. The primary endpoint was treatment effect on intratumoral androgen levels. Secondary endpoints included: PSA levels after 12 weeks of treatment and 6 weeks post-operatively, rates of positive margins, rates of PSA failure, prostate cancer volume, and levels of several serum hormones. RESULTS No significant differences were seen in the intra-prostatic testosterone levels between the 3 arms. Similarly, no differences existed for the intra-prostatic hormone levels of the androgen precursors. However, intra-prostatic dihydrotestosterone levels were significantly higher in Arm A (0.871) versus Arms B (0.258) and C (0.231) (p<0.001). Serum FSH at week 12 was lower for Arms A (0.55) and B (0.65) compared to C (3.65) (p<0.001). Inhibin B serum levels at surgery were also lower in Arms A (89.67) and B (82.14) compared to C (126.67) (p=0.091). Kaplan-Meier survival curve analysis revealed a trend towards improved survival for Arm A (p=0.227). CONCLUSIONS Neoadjuvant use of Degarelix alone is associated with higher levels of dihydrotestosterone in the prostate, despite similar testosterone levels when compared to use of LHRH agonist and Bicalutamide. Degarelix use also leads to significantly lower serum FSH levels. Further studies are needed to clarify this discrepancy in dihydrotestosterone levels; however it may represent adaptive intra-prostatic DHT production secondary to GnRH antagonist treatment. The clinical benefit of these findings remains unclear. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e856 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Rashid Sayyid More articles by this author Martin Gleave More articles by this author Karen Hersey More articles by this author Ranjena Maloni More articles by this author Antonio Hurtado-Coll More articles by this author Andrew Evans More articles by this author Girish Kulkarni More articles by this author Antonio Finelli More articles by this author Alexandre Zlotta More articles by this author Robert Hamilton More articles by this author Michael Jewett More articles by this author Neil Fleshner More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...