The REDUCE trial enrolled over 8,000 patients from 42 different countries around the world. The trial was a randomized, double-blind, placebo-controlled Phase III clinical study. To be eligible to participate in this trial, patients had to meet the following criteria:
- Age between 50 and 75 years
- PSA level of 2.5 to 10 ng/ml
- A single pre-study prostate biopsy that was negative for high-grade prostatic intraepithelial neoplasia (HG-PIN), for ASAP, and for prostate cancer
- A prostate volume ≤ 80 cm3
The authors felt confident that these criteria were defining characteristics for men at high risk.
The results of this trial were published in the New England Journal of Medicine in April 2010, but they were originally presented by the senior investigator at the annual meeting of the American Urological Association in April 2009.
Patients were randomized to treatment with 0.5 mg dutasteride once daily or to a placebo. All patients received protocol-specific, 10-core prostate biopsies at 2 years and at 4 years after study enrollment. However, patients and investigators could decide that individual patients needed to have off-protocol biopsies if these were considered to be necessary. (The incience of such off-protocol biopsies turned out to be very low.)
The top-line results of the trial can be summarized as follows:
- The mean age of the men enrolled was 63 years in each arm
- 91 percent of the patients in each arm were Caucasian
- The mean PSA level of the patients in each arm was 5.9 ng/ml
- On trial entry, patients had an average of 8 negative biopsy cores in their pre-trial biopsy.
- 83 percent of the patients enrolled had at least one on-study biopsy.
- Dutasteride reduced the risk of prostate cancer by 23 percent compared to placebo over the 4 years of the study.
Additional data provided by Dr. Andriole in his presentation were as follows:
- 1,516 patients (22.5 percent) were diagnosed with prostate cancer overall
- 857 of these patients had been treated with placebo
- 659 of these patients had been treated with dutasteride 0.5 mg/day
- 621 patients (9.2 percent) were diagnosed with either HG-PIN or ASAP
- 4,589 patients (88.2 percent) had no disease
- The majority of the prostate cancers were diagnosed in the first two years of the study but …
- The risk reduction was still 23.5 percent when the second round of biopsies were conducted at year 4.
- Subgroup analysis showed that risk reduction was consistent across all risk groups
- There was a 4.3 percent level of drug discontinuation
- The most common side effects of dutasteride were low levels of decrease in libido and erectile dysfunction
- All cases of prostate cancer diagnosed were Gleason score 5 or higher
- There was no significiant increase in the proportion of high-grade tumors (Gleason score 7 to 10 or Gleason score 8 to 10) at 4 years as compared to 2 years.
The “New” Prostate Cancer InfoLink believes that this study provides full validation of the earlier Prostate Cancer Prevention Trial, which used finasteride as the active drug. In the current study we see a very slightly lower level of disease prevention compared to the 26 percent in the PCPT, but the REDUCE trial clearly enrolled a higher risk patient population. We continue to believe that the data from these two trials provide compelling evidence for the value of 5α-reductase inhibitor therapy in the prevention of prostate cancer in carefully selected men believed to be at significant risk for this disease.