Dutasteride slowed the time to prostate cancer progression in men with low-risk, early-stage disease who were followed with active surveillance in the phase III REDEEM study.
Of the 302 patients randomized, 38% of men given dutasteride (Avodart) 0.5 mg daily and 49% of those given placebo experienced some progression of their cancer. This resulted in a relative risk reduction of 38.9% in the dutasteride group, lead author Dr. Neil Fleshner said during a press briefing in advance of the Genitourinary Cancers Symposium.
The aggregate primary end point of the Reduction with Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) study was time to either therapeutic or pathological progression. Therapeutic progression was defined as prostatectomy, radiation, or hormonal therapy. Pathological progression was defined as at least four positive biopsy cores, at least 50% of any one core positive, or a Gleason pattern of 4 or more.
At final biopsy, 36% of 140 men receiving dutasteride had no cancer vs. 23% of 136 men on placebo (P = .024). This is a statistically and clinically significant improvement, said Dr. Fleshner, head of urology at University Health Network in Toronto.
There was no evidence of increased Gleason score progression in patients given dutasteride in the three-year trial, he said. At final biopsy, 12% of men given dutasteride and 14% of those given placebo had a Gleason score of 7, and 2% of men in both groups had a Gleason score of 8. This is noteworthy as an increase in high-grade prostate cancers was observed in men treated with dutasteride compared with those on placebo in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.
Avodart’s maker, GlaxoSmithKline, filed for a chemoprevention indication for dutasteride in the United States and Europe based mainly on the results of REDUCE. It has since announced receiving a Complete Response Letter from the Food and Drug Administration, which signals the indication has not been approved.
Dutasteride and finasteride, another 5-alpha reductase inhibitor, were shot down as prostate chemoprevention agents in December 2010 by the FDA’s Oncologic Drugs Advisory Committee on the basis that the risk-benefit profile for either drug is not favorable when it is used to reduce the risk of prostate cancer.
The current results will not resurrect GSK’s attempt to gain a chemoprevention indication for dutasteride. "They are not going to apply for it," Dr. Fleshner told reporters. "This was not a registration trial, and the time required to reassemble and complete another one will not fit in with their patent expiration. So, I don’t think we will see a formal indication for surveillance."
A separate cost-utility analysis published earlier this month showed that dutasteride at a cost of $626 per year, down from the current cost of $1,400, was unlikely to be cost effective for chemoprevention use in men at elevated risk for prostate cancer (Cancer Prev. Res. 2011;4:277-83).
Press briefing moderator Dr. Nicholas Vogelzang, with US Oncology, Las Vegas, said the paper is important because of the increased anxiety experienced by the growing number of men under watchful waiting.
"With this drug, dutasteride, the PSA [prostate-specific antigen] drops by about 50%; it makes the gland smaller, so they have [fewer] urinary symptoms," he said. "Now we have learned that this seems to reduce the amount of cancer in the gland, and we are now able to offer the patients who wish to have watchful waiting an active treatment option. I think it’s an important step forward."
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