Placebo-controlled dose-ranging phase 2 study of subcutaneously administered LHRH antagonist cetrorelix in patients with symptomatic benign prostatic hyperplasia.
BACKGROUND
Pilot 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).


OBJECTIVE
To assess efficacy and safety of three dosing schemes of CET in patients with symptomatic BPH.


METHODS
After a run-in period with 4 weekly injections of placebo, 140 patients with an international prostate symptoms score (IPSS) > or =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.


METHODS
Patients received either CET at dosages of 5mg/wkx4, 10mg/2 wkx2 or 10mg/wkx4 or placebo.


METHODS
IPSS, 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.


CONCLUSIONS
Of 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.


CONCLUSIONS
At 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/wkx4 regimen. Response persisted up to the end of follow-up, 16 wk after the last dose.
Debruyne
Frans
F
Department of Urology, Academic Hospital Nijmegen, Geert Grooteplein Zuid 16, 426 Afdeling Urologie, 6500 Nijmegen, The Netherlands. f.debruyne@uroweb.org
Gres
Arkadij A
AA
Arustamov
Dmitrii L
DL
D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000008:administration & dosage*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D016896:Treatment Outcome
D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; C062876:cetrorelix