New combination therapies aim at preventing colon cancer

At the American Association for Cancer Research (AACR) Seattle meeting in October, researchers focused on prevention strategies for cancer. Presenters were particularly excited about the potential for new combination therapies to prevent colorectal cancer.

"This approach is very important when a promising chemopreventive demonstrates significant efficacy but may produce some untoward side effects at higher effective doses," said Bandaru Reddy, Ph.D., of the Institute for Cancer Prevention in Valhalla, N.Y. He discussed several such combination therapies during a session at the AACR meeting.

Reddy investigated another duo, piroxicam and difluoromethylornithine (DFMO). The generic name for DFMO is eflornithine, and the drug was formerly marketed by Aventis under the brand name Ornidyl. DFMO is an antiprotozoal used to treat African sleeping sickness. The team gave low doses of these two drugs to rats. They found that both drugs inhibited tumor development, but the two worked better together than separately.

The COX-2 inhibitors have also been studied as chemopreventives. Although they may cause less GI bleeding than NSAIDs, they still have significant adverse effects at high doses, said Reddy. He and his team tested his low-dose combo theory with celecoxib (Celebrex, Pfizer), combining it with a dietary fatty acid supplement, docosahexaenoic acid (DHA). Once again, they administered the drugs separately and in combination and found they were more effective in combination.

Fatty acids are of interest in colon cancer because certain fatty acids appear to cause cancer while others prevent it. In clinical studies, diets high in saturated fats and n-6 polyunsaturated fatty acids (n-6 PUFAs) increased the risk of developing colon cancer. Diets high in fish and fish oils decreased cancer risk, especially if the fish is rich in n-3 PUFAs. Consequently, much research has been done to see whether n-3 PUFA supplements can prevent colon cancer. Reddy said that while this route may be effective in the general population, it might not be effective in high-risk patients. Combination therapy, such as the celecoxib and DHA regimen, might prove to be more suitable for these patients.

Jaye L. Viner, M.D., M.P.H., program director for the gastroenterology and other cancers research group at the National Cancer Institute in Bethesda, Md., concurred that low-dose chemopreventives in combination therapies look promising. There can be some roadblocks in the process, though. Because there are so many potential agents, resources are not available to study all of them. They must be analyzed for potential risks versus benefits to determine which agents seem most promising.

Once a prioritized list of potential chemopreventives is compiled, researchers can look at combining them. The drugs must be screened for pharmacokinetic and pharmacodynamic interactions before any combination studies can be done. Then there are the intellectual property rights attached to the drugs. Negotiating all of this can be a big hurdle, said Viner, but it's not impossible. Combination therapies have been established in other areas, such as cardiovascular disease and AIDS.

Preventing tumors before they start could save millions of Americans from the suffering, expense, and morbidity of cancer and its treatments. If effective low-risk chemopreventive combinations perform well in future trials, cancer prevention, rather than treatment, could be the wave of the future.