Two drugs fail to get FDA approval for prostate cancer prevention.
The long story of chemoprevention for prostate cancer seems to have to come to an anticlimactic end. After two large studies (The Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events study) showing a class of drugs could reduce the risk of prostate cancer but with some unsettling side effects, an advisory panel decided in December not to recommend Avodart (dutasteride) and Proscar (finasteride) for prostate cancer prevention.
Both drugs have already been approved for benign prostatic hyperplasia, or enlarged prostate to reduce urinary side effects from an enlarged prostate; however, a Food and Drug Administration advisory panel seemed uncomfortable approving the drugs for healthy men to prevent prostate cancer.
The two trials showed a relative risk reduction in overall prostate cancer incidence by about a quarter, however there was also a higher incidence of aggressive prostate cancers. In looking at the data, some experts said that decreasing the size of the prostate—which both drugs do—made it easier to find those riskier cancers by biopsy. The advisory panel determined that theory was inconclusive and, citing unknown long-term effects, voted overwhelmingly against approval.
On June 9, the FDA went one step further and revised the drugs’ safety information to include that they may increase the risk of high-grade prostate cancer.
“There is no doubt that finasteride reduces the amount of early-grade prostate cancer that was detected. At the same time, there’s also no doubt that the rates of high-grade prostate cancer were increased, and even the sponsoring companies had to acknowledge they could not exclude the possibility that this drug may have caused that increased risk of high-grade prostate cancer,” said Mikkael Sekeres, MD, during the panel’s vote on Proscar. “And that’s an unacceptable risk in a population of men who don’t have prostate cancer.”
The panel’s decision was followed by a paper published in the February issue of Cancer Prevention Research showing that Avodart was not a cost-effective prevention strategy. While the drug is fairly inexpensive in relative terms—about $1,400 per year—most patients would be taking the medication for decades, and the effect would only benefit about 5 percent of individuals and with no demonstrated effect on cancer mortality. Lower drug costs and restricting the chemoprevention to men deemed at high risk of prostate cancer might make the drug more cost effective, though, the researchers concluded.
The only other approved chemoprevention drugs are Evista (raloxifene) and tamoxifen, which decreases the risk of invasive breast cancer by about half, but has not been popular as a preventive agent because of the potential side effects, cost and inconveniences that come with an ongoing daily medication.