Low-Dose Drug Combination Cuts Risk of Colon Polyp Recurrence

The Bottom Line

Results of a randomized phase III clinical trial show that a combination of low oral doses of the drugs difluoromethylornithine and sulindac greatly reduces the recurrence of colon polyps and is safe and well tolerated.

The Whole Story

Colorectal cancer is the second-leading cause of cancer death in the United States. Research has shown that the removal of precancerous polyps (benign growths that may become cancerous over time) can help lower the risk of colon cancer. However, polyps often recur, or come back. A key goal, therefore, is to identify treatments that will reduce the rate of polyp recurrence.

Results of research with animals and human cells grown in the laboratory has indicated that two drugs, difluoromethylornithine (DFMO) and sulindac (a nonsteroidal anti-inflammatory drug, or NSAID), can inhibit colon carcinogenesis. Animal research has shown further that these drugs may be especially effective when used in combination. Therefore, a phase III clinical trial was conducted to test whether a combination of low oral doses of DFMO and sulindac could reduce the recurrence of colorectal polyps in individuals who had been treated previously to remove such polyps.

In the trial, the researchers randomly assigned 375 individuals from whom at least one colon polyp, or adenoma, had been removed within the previous 5 years to receive either the two-drug combination or placebos. Both drugs were given orally at the lowest possible effective doses. After 3 years, the recurrence of colorectal adenomas was measured by colonoscopy. The results showed that:

• Adenomas recurred in far fewer individuals who took the two drugs (12 percent) than in those who took the placebos (41 percent).
• The presence of advanced adenomas was also much lower in individuals who took the two study drugs (less than 1 percent) than in those who took the placebos (8.5 percent).
• Multiple adenomas were detected in far fewer individuals who took the study drugs (less than 1 percent) than in individuals who took the placebos (13 percent).
• There were no differences in the side effects caused by the study drugs and the placebos.

The effects of the DFMO-sulindac combination were so striking that the trial was stopped early, having conclusively established the benefit of the drug combination on adenoma recurrence. Nevertheless, important questions remain to be answered. In particular, larger studies, with longer follow-up, will need to be conducted to determine whether the drug combination reduces the risk of colorectal cancer itself and whether it increases the risk of heart attack or stroke, as has been seen with some NSAIDs.

Publication: Meyskens FL, McLaren CE, Pelot D, et al. Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial. Cancer Prevention Research 2008; 1(1): 32-38.