SAN DIEGO — A drug once envisioned as a treatment for established cancers might instead help prevent the occurrence of colorectal cancer. Other work suggests the uses for this old drug might extend to a deadly childhood brain cancer.
Scientists first synthesized the drug, DFMO, in 1979, but since then it has developed a reputation as a jack of all trades and master of few. In the 1980s, DFMO showed efficacy in treating African sleeping sickness and eventually got regulatory approval for that use. It also gained clearance as a skin cream to fend off sun-related skin cancer. Otherwise, DFMO seemed to have been lost in the shuffle.
Part of the problem was a curious side effect of the drug. In some patients, it caused subtle, temporary hearing loss.
Now, oncologist Frank Meyskens Jr. of the University of California, Irvine and his colleagues have completed nearly two decades of testing very low doses of DFMO in people who are at high risk for colorectal cancer. Early on, the work showed that at doses only one-fiftieth the amount used to treat cancers, DFMO was safe and patients tolerated it well — and the hearing side effect didn’t show up.
In the recent study, researchers recruited 375 people who had already had precancerous colorectal growths called polyps removed. The scientists randomly assigned some to receive placebo pills and others to get DFMO plus the long-standing anti-inflammatory drug sulindac — both at very low doses. After three years, all participants underwent colonoscopy to determine their polyp status.
The results were so clear that the trial was stopped. About 41 percent of participants receiving placebo pills showed a polyp recurrence, compared with only 12 percent receiving the two-drug treatment. Moreover, 17 people getting placebos had developed more than one polyp while only one receiving the drugs had.
“We’re looking for commercial partners to try to move this drug forward,” says Meyskens, who presented the findings in April in San Diego at a meeting of the American Association for Cancer Research.
DFMO, or difluoromethylornithine, inhibits the synthesis of polyamines, basic compounds in cells. “Elevation of polyamines leads to increased growth, and almost anything like that leads to cancer opportunities,” Meyskens says.
In another study presented at the meeting, researchers in Australia found that DFMO shows promise against neuroblastoma, a brain cancer that preys on children.
Molecular biologist Michelle Haber of Children’s Cancer Institute in Randwick, Australia, reported the results of an experiment in which she and her colleagues induced a form of neuroblastoma in mice. All the animals received a standard chemotherapy drug. But mice also getting DFMO stayed tumor-free longer and survived longer than the other mice. “When polyamine levels are low, it reduces the proliferative capacity of cells,” Haber says.
Old drugs can have new uses, says Roy Herbst, a medical oncologist at the M.D.AndersonCancerCenter in Houston. “We need to look at all our resources. As we uncover the biology [of cancers] we need to look for our best agents that can target those pathways” essential to tumor growth.