RANDOMIZED, DOUBLE BLIND STUDY COMPARING EFFICACY AND TOLERANCE OF VENLAFAXINE VS MEDROXYPROGESTERONE ACETATE VS CYPROTERONE FOR HOT FLUSHES IN MEN UNDER LEUPRORELIN 11.25 MG (ENANTONE) FOR PROSTATE CANCER

Abstract

INTRODUCTION AND OBJECTIVE: One of the most common complaints reported by men under androgen suppression for prostate cancer is hot flushes. We initiated a randomised double blind trial to compare the efficacy of 3 drugs having shown their efficacy against placebo in previous studies. A secondary objective was to evaluate their tolerance METHODS: This is a randomized double blind trial; patients were included in the study and treated for 6 months by Leuprorelin Acetate (Enantone®11.25mg) 3-monthly subcutaneous injection. At 6 month, patients who presented 14 hot flushes or more in the week preceding the visit or those who asked spontaneously for a treatment because of high discomfort due to hot flushes, were randomly assigned to venlafaxine (VLF) or medroxyprogesterone acetate (MPR) or cyproterone acetate (CYP). Evaluation was conducted at inclusion (M0), and then at 6, 7, 8 and 9 months. A daily hot flushes diary was completed one week prior to M6 visit before starting study treatment and throughout the study. The main outcome was the reduction in the score of hot flushes at M7 compared to M6. RESULTS: 919 men were included and 311 were randomized at M6 (102, 101 and108 in the VLF, CYP and MPR groups respectively. Mean age was 73 yrs. The 3 studied drugs reduced hot flushes frequency significantly and 57% of patients were satisfied at M9 in the randomised population. Compliance was good in the 3 arms (> 96%). Hot flushes score relative change (M6-M7) venlafaxine, cyproterone acetate, medroxyprogesterone acetate 29, 3 %, 73,6 %, 73,5 % respectively) P< 0.0001 Comparison two-two of treatment groups: P-value adjusted by bonferoni method (M6-M7) cyproterone acetate vs medroxyprogesterone acetate p< 0.26, cyproterone acetate vs venlafaxine p<.0001 and medroxyprogesterone acetate vs venlafaxine p<.0001 70 patients (23.6%) reported a complete regression of hot flushes after 4 weeks. This percentage was significantly lower in the venlafaxine group (8.3%) compared to the cyproterone acetate (38.1%) and the medroxyprogesterone acetate (24%) groups (p<.001). Number of adverse events per patients was not significatly different in the 3 groups (P=0.33) CONCLUSIONS: Cyproterone acetate, medroxyprogesterone acetate and venlafaxine are effective treatments for hot flushes in prostate cancer patients on GnRH-analogs. Venlafaxine was however less effective than cyproterone acetate and medroxyprogesterone acetate.