Abstract
BackgroundThe value of continuation of luteinizing hormone-releasing hormone (LHRH) therapy in castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking. Argumentation for cessation of LHRH therapy is the prolonged suppression of testosterone levels after the withdrawal of LHRH analogues and the fact that disease progression occurs despite castration levels of testosterone. Especially upon treatment with the life-prolonging cytochrome P450 17-alpha-hydroxylase (Cyp17)-inhibitor, abiraterone, which has the ability to further suppress testosterone serum levels over LHRH therapy alone, continuation of LHRH therapy seems to be negligible. However, the proven increase of luteinizing hormone levels after LHRH withdrawal, which is even further increased by abiraterone, may counteract the effects of abiraterone by the induction of enzymes of steroidogenesis. Therefore, cessation of LHRH therapy when starting treatment with abiraterone in CRPC may display an unpredictable hazard to the patients. This study will explore the role of continuation of LHRH therapy when starting treatment with abiraterone in patients with asymptomatic or mildly symptomatic, chemotherapy-naïve CPRC.Methods/designThe trial will assess radiographic progression-free survival after 12 months of treatment with abiraterone/prednisone in patients who will be randomized to receive continuing LHRH therapy versus LHRH withdrawal at the time of starting abiraterone therapy.DiscussionThis multicenter, prospective, randomized, exploratory phase-II trial will bring about new data regarding the efficacy and safety of abiraterone/prednisone treatment with or without continuation of LHRH therapy. In addition, further insight into the complex hormonal changes under treatment will be gained and the results of this trial may give rise to a larger phase-III trial to examine the possibility of withdrawing LHRH therapy in patients with CRPC.Trial registrationClinicalTrials.gov, ID: NCT02077634. Registered on 9 December 2013.
Highlights
The value of continuation of luteinizing hormone-releasing hormone (LHRH) therapy in castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking
Ohlmann et al Trials (2017) 18:457 (Continued from previous page). This multicenter, prospective, randomized, exploratory phase-II trial will bring about new data regarding the efficacy and safety of abiraterone/prednisone treatment with or without continuation of LHRH therapy
In view of the current available treatment options for CRPC including taxanes, Cytochrome P450 17-alpha-hydroxylase (CYP17) inhibitors and androgenreceptor inhibitors, continuation of LHRH therapy may depend on the actual treatment given
Summary
The value of continuation of luteinizing hormone-releasing hormone (LHRH) therapy in castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking. Cessation of LHRH therapy when starting treatment with abiraterone in CRPC may display an unpredictable hazard to the patients. Inclusion of patients in both phase-III and former trials required continuation of medical castration with luteinizing hormone-releasing hormone (LHRH) therapy in patients who had not undergone prior surgical castration. In medically castrated men treated with abiraterone while continuing on LHRH therapy, testosterone further decreased rapidly to undetectable levels [5]. Cessation of LHRH therapy in patients with castration-resistant prostate cancer is studied insufficiently and, current guidelines advise to continue medical castration [6]. There is little evidence from previous clinical trials that continuation of castration leads to only a marginal, if any, survival benefit [7, 8]
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