The REDUCE trial: chemoprevention in prostate cancer using a dual 5alpha-reductase inhibitor, dutasteride.
Dutasteride, a dual 5alpha-reductase inhibitor, is used in the treatment of benign prostatic hyperplasia (BPH). It reduces serum prostate-specific antigen levels by approximately 50% at 6 months and total prostate volume by 25% after 2 years. Randomized placebo-controlled trials in BPH patients have shown the efficacy of dutasteride in symptomatic relief, improvements in quality of life and peak urinary flow rate. Side effects occurring with dutasteride are decreased libido, erectile dysfunction, ejaculation disorders and gynecomastia. Preliminary data from placebo-controlled BPH trials have shown a decrease in the detection of prostate cancer in patients treated with dutasteride, although these studies were not designed to look at this issue. Dutasteride differs from finasteride in that it inhibits both isoenzymes of 5alpha-reductase, type I and type II. The landmark Prostate Cancer Prevention Trial at the end of the 7-year study demonstrated a 24.8% reduction in the incidence of prostate cancer in the finasteride group compared with placebo. However, a 25.5% increase in the prevalence of high-grade Gleason tumors has been observed, the clinical significance of which has been debated. Preliminary data suggest a decrease in prostate cancer incidence in dutasteride-treated patients and demonstrate type I alphareductase enzyme expression in prostate cancer. As a result, dutasteride is being investigated for prostate cancer prevention in the ongoing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which is discussed here.
Musquera
Mireia
M
University Clinics of Barcelona, c/o Alexandre R Zlotta, Mount Sinai Hospital, Joseph and Wolf Lebovic Building, 60 Murray Street, 6th Floor, Box 19, Toronto, Ontario M5T 3L9, Canada. mireimamusquera@hotmail.com
Fleshner
Neil E
NE
Finelli
Antonio
A
Zlotta
Alexandre R
AR
D058891:5-alpha Reductase Inhibitors; D000368:Aged; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001378:Azasteroids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D000068538:Dutasteride; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011470:Prostatic Hyperplasia / Q000097:blood / Q000188:drug therapy; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D012306:Risk
D058891:5-alpha Reductase Inhibitors; D016588:Anticarcinogenic Agents; D001378:Azasteroids; D007527:Isoenzymes; D017430:Prostate-Specific Antigen; D000068538:Dutasteride