NEW YORK (Reuters Health) - Some men with prostate cancer (PCa) may benefit, at least temporarily, from taking abiraterone acetate with food, rather than on an empty stomach as the label instructions direct, a small study suggests.
The U.S. Food and Drug Administration approved abiraterone in 2011 as a once-daily oral treatment taken with prednisone and without food for metastatic castration-resistant PCa who had failed treatment with docetaxel.
"Outside of a study, I wouldn't recommend necessarily doing this, but we actually showed in our patients that this was safe, we showed no increases in major toxicity and that it bought patients additional months on a study drug that is FDA-approved," Dr. Andrew Armstrong of the Duke Cancer Institute in Durham, North Carolina, told Reuters Health by phone.
"I think it merits attention and prospective studies. It could improve the efficacy of this drug," he said.
Dr. Armstrong and colleagues reviewed data on 60 patients who received abiraterone at their center between 2011 and 2013. Nineteen of those patients switched to taking the drug with food when prostate-specific antigen (PSA) levels began to rise, while 41 patients continued to take it without food.
Of the 19 men who switched, five hadn't responded to abiraterone initially, and they had further PSA increases when administration was changed to "with food" at PSA progression. Fourteen men had initially responded to abiraterone, and after the "with food" switch, three had PSA declines to pre-switch levels. The median time on abiraterone increased by almost 100 days (272 vs. 177 days) in patients who switched to taking the medicine with food, the authors reported online March 17 in Prostate Cancer and Prostatic Disease.
There was no evidence of increased toxicity - but the benefit proved to be temporary.
"The men who responded did so only transiently," Dr. Armstrong said. "The patients who had a food-effect response, while they did have a drop in their PSA, the PSA did go back up again a couple of months later. I don't think this is a dramatic study. For these men, it bought them some additional time, and I think it was of value."
"We were excited just to get this out there. But it is a small clinical observation that might trigger some greater interest," he added.
The next step would be a prospective study to pinpoint the mechanism by which the food effect would lead to a benefit, Dr. Armstrong said.
Abiraterone inhibits CYP17, a key enzyme in the production of androgens. Recent research has suggested that another enzyme, 3-beta-HSD1, is mutated in castration-resistant PCa, and possibly is resistant to abiraterone, Dr. Armstrong said.
"Maybe just taking it with food, if the patient's tumor is dependent on this additional enzyme, we can get higher areas of concentration of the drug safely and inhibit that (enzyme), he explained. "Maybe in some cases we can turn back resistance to (abiraterone) at least for a little while. That's what we saw in about 21% of men."
Understanding the mechanism may help with future studies, he said. "It could be higher drug levels. It could be blocking this new enzyme. It's likely one of the two. Identifying that ahead of time in a prospective study would be the next step."
Dr. Armstrong has been an advisor and consultant to Janssen Pharmaceutica, maker of abiraterone; another author reported receiving research support from Janssen.
SOURCE: http://bit.ly/19eSVUK
Prostate Cancer Prostatic Dis 2015.
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