A phase 3, multicenter, open-label, randomized study of abarelix versus leuprolide acetate in men with prostate cancer.
OBJECTIVE
To evaluate the levels of testosterone and other hormones in men with prostate cancer treated with abarelix versus leuprolide acetate.


METHODS
Patients (n = 269) were randomized to receive open-label abarelix 100 mg or leuprolide acetate 7.5 mg by intramuscular injection. The results of the first 84 days of the study are reported. The primary efficacy endpoints included avoidance of testosterone surge, castration on day 8, and achievement and maintenance of castration from days 29 through 85. The secondary endpoints included castration on days 2, 4, and 15; a reduction in prostate-specific antigen level; and measurements of other hormones. Patients were monitored for clinical adverse events and laboratory abnormalities.


RESULTS
No men in the abarelix group and 82% of men in the leuprolide acetate group experienced a testosterone surge (P <0.001). Abarelix caused rapid medical castration: 24% of men 1 day after treatment and 78% after 7 days compared with 0% of men treated with leuprolide acetate on either day. A comparable percentage of men achieved and maintained castration between days 29 and 85 in each group. Prostate-specific antigen had a statistically significant decrease for the first month in patients treated with abarelix. Dihydrotestosterone, luteinizing hormone, prostate-specific antigen, and follicle-stimulating hormone showed similar rapid reductions without an initial increase. The overall occurrence of adverse events was similar across the treatment groups, and most were sequelae of comorbid disorders.


CONCLUSIONS
Treatment with abarelix produced a higher percentage of patients who avoided a testosterone surge and had a more rapid time to testosterone suppression with a higher rate of medical castration 1 day after treatment and greater reductions in testosterone, luteinizing hormone, follicle-stimulating hormone, and dihydrotestosterone during the first 2 weeks of treatment compared with leuprolide acetate. The achievement and maintenance of castration was comparable between the two groups.
McLeod
D
D
Walter Reed Army Medical Center, Washington, DC, USA.
Zinner
N
N
Tomera
K
K
Gleason
D
D
Fotheringham
N
N
Campion
M
M
Garnick
M B
MB
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002369:Castration; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007273:Injections, Intramuscular; D016729:Leuprolide / Q000009:adverse effects / Q000627:therapeutic use*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood*; D013997:Time Factors
D000970:Antineoplastic Agents; D015415:Biomarkers; D009842:Oligopeptides; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D017430:Prostate-Specific Antigen; D016729:Leuprolide; C423508:abarelix