Degarelix versus Goserelin (+ Antiandrogen Flare Protection) in the Relief of Lower Urinary Tract Symptoms Secondary to Prostate Cancer: Results from a Phase IIIb Study (NCT00831233)

Abstract

Introduction: No studies to date have assessed the efficacy/tolerability of degarelix in the relief of lower urinary tract symptoms (LUTS) secondary to prostate cancer (PrCa). Methods: Patients were randomised to degarelix 240/80 mg or goserelin 3.6 mg + bicalutamide flare protection (G+B); both treatments were administered for 3 months. The primary endpoint was change in International Prostate Symptom Score (IPSS) at week 12 compared with baseline. Results: This study was stopped early due to recruitment difficulties. 40 patients received treatment (degarelix n = 27; G+B n = 13); most had locally advanced disease and were highly symptomatic. Degarelix was non-inferior to G+B in reducing IPSS at week 12 in the full analysis set (p = 0.20); the significantly larger IPSS reduction in the per-protocol analysis (p = 0.04) was suggestive of superior reductions with degarelix. Significantly more degarelix patients had improved quality of life (IPSS question) at week 12 (85 vs. 46%; p = 0.01). Mean prostate size reductions at week 12 were 42 versus 25% for patients receiving degarelix versus G+B, respectively (p = 0.04; post hoc analysis). Most adverse events were mild/moderate; more degarelix patients experienced injection site reactions whereas more G+B patients had urinary tract infections/cystitis. Conclusion: In 40 men with predominantly locally advanced PrCa and highly symptomatic LUTS, degarelix was at least non-inferior to G+B in reducing IPSS at week 12.

A prospective, observational grouped analysis to evaluate the effect of triptorelin on lower urinary tract symptoms in patients with advanced prostate cancer

“…Furthermore, the GnRH antagonist degarelix had a greater impact on LUTS at 12 weeks compared with the GnRH agonist goserelin, despite similar effects on PSA and testosterone suppression, which may suggest the mechanism on LUTS is independent of these markers Anderson et al 2013;Mason et al 2013;Cui et al 2014]. Although prostate volume was not measured in this observational study, there was a clear correlation between PSA suppression and LUTS improvement in this large cohort of patients.…”

Degarelix versus Goserelin plus Bicalutamide Therapy for Lower Urinary Tract Symptom Relief, Prostate Volume Reduction and Quality of Life Improvement in Men with Prostate Cancer: A Systematic Review and Meta-Analysis

“…One article lacked useful data (the values of IPSS, TPV and QoL). In total, three articles [11,12,13] with three RCTs were included in the analysis to compare degarelix with goserelin plus bicalutamide over 12 weeks. The baseline characteristics of the studies and patients included in our meta-analysis are listed in tables 1 and 2.…”

Clinical pharmacology and regulatory consequences of GnRH analogues in prostate cancer

“…Abarelix (Plenaxis®) was approved by the FDA in 2003. Compared to GnRH analogues, the castration level usually is reached without initial testosterone flare-up within 1 week (+antiandrogen flare protection) in the relief of lower urinary tract symptoms secondary to prostate cancer: results from a phase IIIb study (NCT00831233) [20]. In clinical trials, one third of patients even reached castration level after 3 days.…”