Placebo-Controlled Dose-Ranging Phase 2 Study of Subcutaneously Administered LHRH Antagonist Cetrorelix in Patients with Symptomatic Benign Prostatic Hyperplasia

Abstract

BackgroundPilot studies with daily dosing suggested the use of the luteinizing hormone-releasing hormone antagonist cetrorelix (CET) for the treatment of symptoms from benign prostatic hyperplasia (BPH). ObjectiveTo assess efficacy and safety of three dosing schemes of CET in patients with symptomatic BPH. Design, Setting and ParticipantsAfter a run-in period with 4 weekly injections of placebo, 140 patients with an international prostate symptoms score (IPSS) ≥13 and a peak urinary flow rate (PFR) 5–13ml/s were randomly allocated to 4 treatment groups; patients with residual urine volume of >350ml were excluded. InterventionPatients received either CET at dosages of 5mg/wk×4, 10mg/2 wk×2 or 10mg/wk×4 or placebo. MeasurementsIPSS, PFR and mean uroflow, residual urinary volume, prostate volume, plasma testosterone, quality of life, and sexual function were evaluated over a total of 20 wk after randomization. Results and LimitationsOf 140 randomized patients, one patient did not complete treatment, 5 others dropped out off-treatment, before week 12 evaluation of the primary end point. In all CET groups a rapid improvement in mean IPSS was obtained, with a peak effect of −5.4 to −5.9 (placebo: −2.8). After all dosages of CET given, changes from baseline and differences to placebo were statistically significant up to week 20. Similarly, secondary parameters showed a significant, rapid, and persistent improvement for all CET dosages. All dosage regimens were well tolerated. The study evaluated a single treatment course only; further studies with repeated treatment courses will be required to establish a dose regimen for long-term disease management. ConclusionsAt all dosage regimens tested, CET was safe and effective in patients with symptomatic BPH, with a trend towards a more rapid onset of effect for the CET 10mg/wk×4 regimen. Response persisted up to the end of follow-up, 16 wk after the last dose.