Rashid K Sayyid 1 , Andrew Evans 1 , Karen Hersey 1 , Ranjena Maloni 1 , Antonio Hurtado-Coll 2 , Girish Kulkarni 1 , Antonio Finelli 1 , Alexandre R Zlotta 1 , Robert Hamilton 1 , Martin Gleave 2 , Neil E Fleshner 3 Show Affiliations »
Abstract
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Purpose: Degarelix , a new gonadotropin-releasing hormone (GnRH) receptor antagonist with demonstrated efficacy as first-line treatment in the management of high-risk prostate cancer, possesses some theoretical advantages over luteinizing hormone-releasing hormone (LHRH ) analogues in terms of avoiding "testosterone flare" and lower follicle-stimulating hormone (FSH) levels . We set out to determine whether preoperative degarelix influenced surrogates of disease control in a randomized phase II study.Experimental Design: Thirty-nine patients were randomly assigned to one of three different neoadjuvant arms: degarelix only, degarelix/bicalutamide, or LHRH agonist/bicalutamide . Treatments were given for 3 months before prostatectomy. Patients had localized prostate cancer and had chosen radical prostatectomy as primary treatment . The primary end point was treatment effect on intratumoral dihydrotestosterone levels .Results: Intratumoral DHT levels were higher in the degarelix arm than both the 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 the degarelix -only arm had higher AMACR levels on immunohistochemical analysis (P = 0.01). Serum FSH levels were lower after 12 weeks of therapy in both degarelix arms than the LHRH agonist/bicalutamide arm (0.55 and 0.65 vs. 3.65, P < 0.01), and inhibin B levels were lower in the degarelix/bicalutamide arm than the LHRH agonist/bicalutamide arm (82.14 vs. 126.67, P = 0.02).Conclusions: Neoadjuvant degarelix alone, compared with 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. Clin Cancer Res; 23(8); 1974-80 . ©2016 AACR. ©2016 American Association for Cancer Research.
RCT Entities: Population
Interventions
Outcomes
Purpose: Degarelix , a new gonadotropin-releasing hormone (GnRH) receptor antagonist with demonstrated efficacy as first-line treatment in the management of high-risk prostate cancer , possesses some theoretical advantages over luteinizing hormone-releasing hormone (LHRH ) analogues in terms of avoiding "testosterone flare" and lower follicle-stimulating hormone (FSH) levels. We set out to determine whether preoperative degarelix influenced surrogates of disease control in a randomized phase II study.Experimental Design: Thirty-nine patients were randomly assigned to one of three different neoadjuvant arms: degarelix only, degarelix /bicalutamide , or LHRH agonist/bicalutamide . Treatments were given for 3 months before prostatectomy. Patients had localized prostate cancer and had chosen radical prostatectomy as primary treatment. The primary end point was treatment effect on intratumoral dihydrotestosterone levels.Results: Intratumoral DHT levels were higher in the degarelix arm than both the 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 the degarelix -only arm had higher AMACR levels on immunohistochemical analysis (P = 0.01). Serum FSH levels were lower after 12 weeks of therapy in both degarelix arms than the LHRH agonist/bicalutamide arm (0.55 and 0.65 vs. 3.65, P < 0.01), and inhibin B levels were lower in the degarelix /bicalutamide arm than the LHRH agonist/bicalutamide arm (82.14 vs. 126.67, P = 0.02).Conclusions: Neoadjuvant degarelix alone, compared with 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. Clin Cancer Res; 23(8); 1974-80. ©2016 AACR. ©2016 American Association for Cancer Research.
Entities: Chemical
Disease
Gene
Species
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Year: 2016
PMID： 27756786 DOI： 10.1158/1078-0432.CCR-16-1790
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 12.531