WASHINGTON — The FDA has issued a warning of an increased risk of high-grade prostate cancer with the 5-alpha reductase inhibitors finasteride (Proscar) and dutasteride (Avodart), currently approved to treat benign prostatic hypertrophy.
The agency announced Thursday that it has updated the Warnings and Precautions section of labels for the class of drugs — which includes branded products Propecia and Jalyn under which finasteride and dutasteride are marketed for other indications — to reflect the increased risk.
“This risk appears to be low, but healthcare professionals should be aware of this safety information, and weigh the known benefits against the potential risks when deciding to start or continue treatment with 5-ARIs in men,” the agency wrote in its safety announcement.
Avodart, Jalyn, and Proscar are approved to treat symptoms of an enlarged prostate. Propecia, at a 1-mg dose, is approved to treat hair loss in men.
The announcement follows the FDA’s Oncologic Drugs Advisory Committee’s vote of 17-0 in December that GlaxoSmithKline’s dutasteride and Merck’s finasteride should not be used to prevent prostate cancer because the drugs are linked to a higher incidence of high-grade tumors.
GlaxoSmithKline was seeking to expand dutasteride’s indication to include reducing the risk of prostate cancer in men who have had a prior negative biopsy and who have an elevated PSA.
Merck hadn’t been seeking an expanded indication, but the company wanted to update the label of finasteride to detail positive results of the Prostate Cancer Prevention Trial (PCPT), which demonstrated the drug’s chemopreventive potential.
Although the 5-alpha reductase inhibitors were shown to prevent low-risk cancers better than placebo, two large clinical trials painted a disturbing link between both drugs and an increased incidence of higher-risk prostate cancers.
Taken together, data from the trials — the PCPT and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial — showed the 5-alpha reductase inhibitors both provided a statistically significant reduction in the cumulative incidence of prostate cancer after four years (REDUCE) and seven years (PCPT) of treatment with dutasteride and finasteride, respectively.
But both trials also found an unexpected increase in the incidence of high-grade prostate cancers among men receiving the 5-alpha reductase inhibitors.
In the REDUCE trial, 29 high-grade tumors were found among patients being treated with dutasteride compared with 19 in the placebo group.
In the PCPT, there was a 26% decrease in all prostate cancers but an absolute increase of 1.3% in the incidence of high-grade tumors.
According to an FDA statistician who spoke at the December advisory committee meeting, if 200 men are treated with the drugs, it is expected that there will be one additional tumor with a Gleason score of 8 to 10.
How to handle low-grade prostate cancer is controversial in the urology community, in part because it is unknown if the low-grade tumors would ever develop into high-grade tumors, and also because the method used to originally detect prostate cancer — the PSA test — is inexact.
About five million men received a prescription for a 5-ARI between 2002 and 2009, according to the FDA.