A Phase II, Randomized, Open-Label Study of Neoadjuvant Degarelix versus LHRH Agonist in Prostate Cancer Patients Prior to Radical Prostatectomy
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Rashid K Sayyid1, Andrew Evans1, Karen Hersey1
1Princess Margaret Cancer Centre, Toronto, Canada.
Abstract:
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.
Insights
Neoadjuvant degarelix, a GnRH antagonist, resulted in higher intratumoral DHT levels in prostate cancer patients compared to LHRH agonists. Further research is needed to understand these findings in prostate cancer management.
Area of Science:
- Oncology
- Endocrinology
- Urology
Background:
- Degarelix is a gonadotropin-releasing hormone (GnRH) receptor antagonist used for high-risk prostate cancer.
- It offers theoretical advantages over luteinizing hormone-releasing hormone (LHRH) analogues, including avoiding testosterone flare and lowering follicle-stimulating hormone (FSH).
- Preoperative (neoadjuvant) treatment strategies are crucial in managing localized prostate cancer before radical prostatectomy.
Purpose of the Study:
- To evaluate the influence of neoadjuvant degarelix on surrogates of disease control in patients with localized prostate cancer.
- To compare intratumoral dihydrotestosterone (DHT) levels following treatment with degarelix alone, degarelix/bicalutamide, or LHRH agonist/bicalutamide.
- To assess the impact of these neoadjuvant therapies on other intratumoral androgens and serum hormonal markers.
Main Methods:
- A randomized phase II study involving 39 patients with localized prostate cancer.
- Patients were assigned to neoadjuvant treatment arms for 3 months prior to prostatectomy: degarelix only, degarelix/bicalutamide, or LHRH agonist/bicalutamide.
- The primary endpoint was the effect on intratumoral DHT levels; other androgens, AMACR, FSH, and inhibin B were also measured.
Main Results:
- Intratumoral DHT levels were significantly higher in the degarelix-only arm compared to both degarelix/bicalutamide and LHRH agonist/bicalutamide arms (P < 0.01).
- No significant differences were observed in other intratumoral androgens (testosterone, dehydroepiandrosterone).
- Serum FSH levels were lower in degarelix arms post-therapy, while inhibin B was lower in the degarelix/bicalutamide arm compared to LHRH agonist/bicalutamide.
Conclusions:
- Neoadjuvant degarelix monotherapy is associated with elevated intratumoral DHT levels compared to LHRH agonist and bicalutamide combinations.
- Despite similar testosterone levels, degarelix treatment resulted in higher intratumoral DHT, suggesting complex hormonal interactions.
- Further investigation into the mechanisms underlying these hormonal changes is warranted for optimizing prostate cancer treatment strategies.
