The Effects of the Dual 5 Alpha -Reductase Inhibitor Dutasteride on Localized Prostate Cancer - Results From a 4-Month Pre-Radical Prostatectomy Study
Written by Christopher P. Evans, MD
Monday, 02 October 2006
BERKELEY, CA (UroToday.com) - Finasteride, a 5- reductase inhibitor reduced the prevalence of prostate cancer (CaP) in the Prostate Cancer Prevention Trial.
Dr. Gleave and associates evaluate the histopathological effects of 4-months neoadjuvant treatment with another 5- reductase inhibitor, dutasteride in men undergoing radical prostatectomy (RP). Their report appears in the epub version of The Prostate.
In a randomized 3-arm trial, men received 0.5mg dutasteride, 3.5mg dutasteride or no treatment prior to RP. Investigators were blinded to dutasteride dosage. Participants returned for clinical assessment at 2 weeks, 2 months and 4 months after randomization. Serum PSA and serum and intraprostatic DHT and testosterone were measured. Other parameters included prostate volume, and central pathologic review of biopsies and surgical specimens. RP specimens were scored for degree of apoptosis, proliferation, atrophy, microvessel density, tumor grade among other parameters. The primary study endpoint was degree of apoptosis.
Mean total serum PSA was 6.2and median Gleason score was 6. A total of 75 participants completed the study. Treatment with dutasteride at 0.5mg and 3.5mg suppressed serum DHT 90% and 92%, respectively and testosterone rose by 16% and 21%, respectively. Surgery alone patients had no change in DHT and a 5% increase in testosterone. Mean intraprostatic DHT levels were decreased by 93% and 99% in the 0.5mg and 3.5mg groups. Intraprostatic testosterone levels increased in these men.
Serum PSA in the RP only group changed little prior to surgery (6%), but in the dutasteride 0.5mg and 3.5mg groups a decrease of 47% and 58%, respectively were found. Dutasteride treatment was associated with increased amount of atrophic epithelium, but only statistically so for the 0.5mg dutasteride group. The primary endpoint, apoptosis staining, demonstrated mixed results by the two methods. Tissue transglutaminase staining suggested a trend to increased apoptosis in dutasteride treated patients versus surgery alone, while TUNEL staining demonstrated a significant decrease in apoptosis in treated subjects.
Dutasteride treatment decreased prostate volume and serum PSA, consistent with know effects. The data suggests that dutasteride treatment results in similar effects as androgen deprivation therapy, but to a lesser extent.
The Prostate 66(15);1674 - 1685
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