Intermittent dosing may shrink melanomas
San Francisco — Intermittent dosing of vemurafenib extended the lives of lab mice with drug-resistant melanoma tumors, according to results of an international study.
Researchers with University of California, San Francisco, Novartis Institutes for Biomedical Research, Emeryville, Calif., and University Hospital Zurich, found that adjusting the dosing of vemurafenib (Zelboraf, Genentech) and using an “on-again, off-again” schedule prolonged the lives of mice with melanoma tumors, Newswise reports.
The investigators learned that a mechanism by which melanoma cells become resistant to vemurafenib also causes them to become hooked on the drug, resulting in the cells using vemurafenib to cause a growth in rapidly progressing drug-resistant tumors.
The researchers theorized that if the melanoma cells resistance to the drug also caused it to become “addicted” to it, the drug-resistant tumors might shrink when vemurafenib is eliminated. When the investigators stopped giving the drug to mice with resistant tumors, the tumors shrank again. Mice that were continuously treated with vemurafenib died of drug-resistant disease within about 100 days, Newswise reports, but those mice given drug holidays lived beyond 100 days.
“These data highlight the concept that drug-resistant cells may also display drug dependency, such that altered dosing may prevent the emergence of lethal drug resistance,” study authors wrote. “Such observations may contribute to sustaining the durability of the vemurafenib response with the ultimate goal of curative therapy for the subset of melanoma patients with BRAF mutations.”
The study was published online Jan. 9 in Nature.