ORLANDO, FL—The 5-alpha reductase inhibitor (5-ARI) dutasteride reduced the risk of progression by nearly 40% in patients with low-risk prostate cancer on active surveillance, researchers reported here at the Genitourinary Cancers Symposium, a meeting cosponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.
In the study of 302 patients, about half of those given placebo had disease progression, compared with just over one-third given dutasteride, reported Neil Fleshner, MD, Head of Urology at the University Health Network in Toronto.
Additionally, men on dutasteride were significantly more likely to have no evidence of cancer at final biopsy three years after entering the study.
Used to treat benign prostatic hyperplasia, the 5-ARIs have also been studied as chemopreventive agents due to their action in reducing levels of dihydrotestosterone (DHT).
Large randomized trials have shown that treatment with dutasteride reduced the risk of prostate cancer in men at high risk and that its cousin finasteride reduced the incidence in men at low or average risk.
However, an FDA advisory committee in December voted against giving approval for either 5-ARI to expand the indication to include prostate cancer prevention, citing evidence of an increased risk of high-grade cancer among men treated with the drugs (OT 1/10/11 issue). The vote against dutasteride was made final by the full FDA in January.
The new study, known as REDEEM—Reduction with Dutasteride of Clinical Progression Events in Expectant Management—was designed to investigate another potential use for dutasteride: as an adjunct to active surveillance in men with early prostate cancer.
“This could be one of the best uses of these drugs—Let's find men with clinically insignificant cancers and give the drugs, not to prevent cancer, but to prevent the progression,” Dr. Fleshner said.
The 302 men in the study were age 48 to 82, with low-risk prostate cancer, defined as clinical stage T1c–T2a, a PSA level of less than 11 ng/mL, and a Gleason score of 6 or less.
All the men had opted for active surveillance, or watchful waiting. Patients were randomized to placebo or dutasteride (0.5 mg daily) and followed for three years.
Participants had 12-core prostate biopsies at baseline and at 12 and 36 months.
The primary endpoint was time to disease progression, defined as pathologic progression (Gleason score over 6, four or more positive cores, or more than 50% of any core positive) or therapeutic progression (need for treatment with radical prostatectomy, radiation therapy, and/or hormonal ablation).
A total of 38% of men in the dutasteride group had disease progression vs 49% of the placebo group. This corresponds to a significant, 38.9% reduction in the relative risk of progression, Dr. Fleshner reported.
On the final biopsy, there was no evidence of cancer in 36% of the men in the dutasteride group, compared with 23% of the placebo group.
Importantly, there was no evidence of an increased risk of high-grade cancer among men taking dutasteride, he said. On final biopsy, only three men in the placebo group and two in the dutasteride group had a Gleason score of 8, and none had a score of 9 or 10.
As measured using the Memorial Anxiety Scale for Prostate Cancer, patients taking dutasteride had significantly less prostate-cancer-related anxiety than those on placebo.
This finding is extremely important as men who opt for active surveillance experience high levels of anxiety, even though research has shown that men with early-stage prostate cancer are 20 times more likely to die of something other than their cancer, commented Nicholas J. Vogelzang, MD, Chair and Medical Director of the Developmental Therapeutics Committee of US Oncology in Las Vegas.
The anxiety can drive men to seek active treatment when it is not necessary, he said.
“With dutasteride, the PSA drops, generally by about 50%. Seeing the PSA drop is almost orgasmic for some patients,” Dr. Vogelzang said.
“Dutasteride makes the prostate gland smaller so men have fewer urinary symptoms.
“Now we have learned that this seems to reduce the amount of cancer in the gland, and we are now able to offer patients who wish to have watchful waiting an active treatment option.”
Even so, dutasteride is not likely to be approved by the FDA for this use, Dr. Fleshner said. “The FDA shot down the prevention model”—that is, use of 5-alpha reductase inhibitors for prostate cancer prevention, he said.
The study was funded by GlaxoSmithKline.