A Phase II, Randomized, Open Label Study of Neoadjuvant Degarelix versus LHRH Agonist in Prostate Cancer Patients Prior to Radical Prostatectomy

Degarelix, a new GnRH receptor antagonist with demonstrated efficacy as 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.

39 patients were randomly assigned to one of 3 different neo-adjuvant arms: degarelix only, degarelix/bicalutmaide, or LHRH agonist/bicalutamide. Treatments were given for 3 months prior to prostatectomy. Patients had localized prostate cancer and had chosen radical prostatectomy as primary treatment. The primary endpoint was treatment effect on intratumoral dihydrotestosterone levels.

Intratumoral DHT levels were higher in degarelix arm compared to both degarelix/bicalutamide and LHRH agonist/bicalutamide arms (0.87 ng/g vs. 0.26 ng/g and 0.23 ng/g, p<0.01). No significant differences existed for other intratumoral androgens, such as testosterone and dehydroepiandrosterone. Patients in degarelix only arm had higher AMACR levels on immunohistochemical analysis (p=0.01). Serum FSH levels were lower after twelve weeks of therapy in both degarelix arms compared to LHRH agonist/bicalutamide arm (0.55 and 0.65 vs. 3.65, p<0.01) and inhibin-B levels were lower in degarelix/bicalutamide arm compared to LHRH agonist/bicalutamide arm (82.14 vs. 126.67, p=0.02).

Neoadjuvant degarelix alone, compared to use of LHRH agonist and bicalutamide, is associated with higher levels of intratumoral dihydrotestosterone, despite similar testosterone levels. Further studies that evaluate the mechanisms behind these results are needed.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2016 Oct 18 [Epub ahead of print]

Rashid Sayyid, Andrew Evans, Karen Hersey, Ranjena Maloni, Antonio Hurtado-Coll, Girish Kulkarni, Antonio Finelli, Alexandre R Zlotta, Robert Hamilton, Martin Gleave, Neil Fleshner

Urology, Princess Margaret Hospital., 1Departments of Radiation Oncology, Medical Biophysics, Medical Oncology,Laboratory Medicine and Pathology and Biostatistics, University of Toronto., LAGA, Vancouver Prostate Centre., Dept of Surgery (Urology), Princess Margaret Cancer Centre, University Health Network., Departments of Surgery of Oncology, University of Toronto., Surgery-Urology, Mount Sinai Hospital., Department of Surgery, Princess Margaret Cancer Center, University of Toronto., Jack Bell Vancouver General Hospital, The Vancouver Prostate Research Centre., Urology, Princess Margaret Hospital .