April 15, 2008 (San Diego) -- A combination of the targeted anticancer agent DFMO and the antiarthritis drug sulindac reduces the risk of recurrent colon polyps by up to 95%, researchers report.
Importantly, the combination was associated with less toxicity than chemotherapy, says study head Frank Meyskens, MD, director of the Cancer Center at the University of California at Irvine.
"This is the best thing that's come along for colon cancer prevention in 20 years," he tells WebMD.
The combination treatment worked so well that the study was halted early.
"We're all pretty excited," says Roy Herbst, MD. "The data is pretty extraordinary."
The study was presented here at the annual meeting of the American Association for Cancer Research. Herbst, a cancer specialist at the University of Texas M.D. Anderson Cancer in Houston, moderated the session.
Colorectal cancer will strike about 150,000 Americans in 2008. It will kill about 50,000 men and women, according to the American Cancer Society.
Reduction in Risk of Multiple Colon Growths
Meyskens and colleagues studied 375 people who had at least three colorectal polyps, also known as adenomas, removed.
They were randomly assigned to treatment with either a combination of DFMO and sulindac, or placebo.
After three years, colonoscopy exams showed that 12.3% of patients given the drug combination had developed a new polyp, compared with 41.1% of patients given a placebo. This translates to a 70% reduction in risk.
"Even more remarkable was that there was a 92% reduction in the risk of advanced adenomas that are more likely to go on to cancer," Meyskens says. A total of 0.7% of patients in the treatment group had advanced adenomas -- such as those that are 1 centimeter in size or larger or have signs of abnormal cell growth under the microscope (dysplasia) -- vs. 8.5% in the placebo group.
"The real home run: A 95% reduction in multiple adenomas," Meyskens says. A total of 0.7% of patients in the treatment group developed more than one adenoma, versus 13.2% in the placebo group.
There was no significant difference in the rate of serious side effects, including heart attacks and strokes, between the two groups.
Use Foreseen in People at High Risk of Colon Cancer
Meyskens says that DFMO, which is short for difluoromethylornithine, was developed as a cancer medication, but is now used to treat African sleeping sickness. It's also used to remove unwanted hair. Sulindac, a non-steroidal anti-inflammatory drug (NSAID), is also sold as Clinoril.
Meyskens says that further study is needed to confirm both the safety and effectiveness of the combo treatment. But he thinks it will eventually be used to help prevent colon cancer in "people at highest risk, such as people with advanced adenoma on colonoscopy."
It may also prove useful for "people with early colon cancer who have been cured. Without treatment, about one-third will go on to have another colon cancer," he says.
Celebrex Also Slashes Polyp Risks
But that research also showed that people taking Celebrex had more heart attacks, stroke, and other cardiovascular problems, particularly if they already had heart disease.
The researchers followed people who were involved in a study that was terminated early after Celebrex was linked to an increased risk of cardiovascular problems.
Participants took either 200 milligrams or 400 milligrams of Celebrex, or a placebo, twice a day, for three years. About 600 of them had a follow-up colonoscopy an average of one-and-one-half years after stopping the drug.
"At three years, there was about a 57% reduction in the presence of new advanced lesions in patients on the lower dose of Celebrex," says Monica Bertagnolli, MD, associate professor of surgery at the Brigham and Women's Hospital in Boston.
By an average of one-and-one-half years after discontinuing treatment, there was still a 41% reduction in advanced lesions among people on the lower dose of Celebrex, she tells WebMD
The higher dose was no more effective than the lower dose, Bertagnolli says.
Heart Safety of Celebrex Is a Concern
"Almost any way you look at it, there is some cardiovascular risk associated with Celebrex. So we can't say the 200-milligram, twice-daily dose, is completely safe. We can say that neither dose should be used by patients with cardiovascular risk factors," Bertagnolli says.
So what about people at low risk of heart problems but high risk of colon cancer?
That's a muddy area, she says.
"For people at high risk, such as those who have had multiple, large adenomas removed, we can certainly say it is certainly effective," Bertagnolli tells WebMD.
The risks to the heart have to be weighed against the cancer-prevention benefits, she says.
Scott Lippman, MD, of the University of Texas M.D. Anderson Cancer Center in Houston and a participant at both presentations, tells WebMD: "These are two of the most important trials in cancer prevention research. They will take us into the future."
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