Study shows aspirin can help prevent polyps in colorectal cancer patients

Taking one aspirin a day can prevent the development of precancerous polyps in patients at increased risk for colorectal cancer, according to a study by University researchers and colleagues published in today’s issue of the New England Journal of Medicine. Aspirin’s protective effect was so significant that the study was stopped early.

Conceived and organized by Cancer and Leukemia Group B, this study and a related one published in the same issue provide a significant boost to the mounting evidence that aspirin and related drugs can reduce the risk of colon cancer–the second-leading cancer killer.

“Aspirin had a significant protective effect,” said senior author Richard Schilsky, Professor in Medicine at the University and chairman of Cancer and Leukemia Group B. “It clearly reduced the formation of polyps in this study of high-risk individuals, which is good news because it provides a new way to lower the risk of recurrence in patients who have had colon cancer.”

An aspirin a day, the researchers found, reduced the occurrence of adenomas, precancerous polyps in the colon, by about one-third in patients with a history of colorectal cancer. Patients on aspirin who did get polyps took longer to develop them, and they had fewer polyps than those who did not take aspirin.

“This suggests,” Schilsky added, “that aspirin and similar anti-inflammatory drugs may help prevent this disease in average-risk individuals.” Although these drugs are not without risks, many people already take a daily aspirin to prevent cardiovascular disease. “Now we have one more reason,” he said, “to consider recommending aspirin for prevention in patients with no contraindications.”

Robert Sandler, professor of medicine and epidemiology at the University of North Carolina, said: “We are not suggesting that even those with increased cancer risk take aspirin until they have discussed it with their doctors.” Sandler, who was the lead author of the Cancer and Leukemia Group B paper and a co-author of the second study, added: “For those who have had polyps or previous colon cancer, regular colonoscopy and polyp removal remain the first step in prevention, possibly supplemented by aspirin.”

he American Cancer Society estimates that colorectal cancer will be diagnosed in about 147,500 people in the United States in 2003 and cause 57,100 deaths.

Although epidemiological studies in the early 1990s found that regular aspirin users, such as patients with arthritis, have less colon cancer than usual, the first large-scale controlled trials providing direct evidence of prevention are just being completed.

The initial trials involved patients at extremely high risk, those with a genetic disorder known as familial adenomatous polyposis, or FAP. People with FAP get hundreds of polyps that almost always progress to cancer by age 30. Celecoxib (Celebrex®), an anti-inflammatory drug similar to aspirin, reduced the development of polyps in patients with FAP by 28 percent and was approved by the FDA for this use in December 1999.

The two long-awaited studies published in today’s New England Journal of Medicine looked at slightly different groups at intermediate risk. In the Cancer and Leukemia Group B study, the researchers focused on patients who had previously had surgery for colorectal cancer but appeared to be cured. These people are very likely to develop new adenomas, which often progress to cancer. The other study looked at people who previously had precancerous polyps removed, but who had not been diagnosed with colorectal cancer.

The Cancer and Leukemia Group B study followed 517 patients with cancers that had been removed surgically. Although cured of their original tumors, these patients–none of whom had polyps at the beginning of the study–were at increased risk of developing new adenomas, which could develop into new cancers.

Half of these patients were assigned to take one coated aspirin a day and the rest to take a placebo. All patients had at least one colonoscopy performed about a year into the study, part of the standard follow-up for patients with colorectal cancer. Most had additional colon exams after 24 to 30 months.

During the three-year study, 17 percent (43 out of 259) of those taking aspirin and 27 percent (70 out of 258) of those getting the placebo developed adenomas.

The patients on aspirin who developed polyps had fewer of them. Twenty-six (10 percent) had one adenoma, nine (3 percent) had two, and eight (3 percent) had three. For patients not getting aspirin, 37 (14 percent) had one polyp, 19 (7 percent) had two and 14 (5 percent) had three.

Side effects, such as gastrointestinal bleeding or ulcers, were similar for each group.

The other study published in the journal also showed that aspirin could reduce the growth of polyps, but it found that a lower dose, 80 milligrams instead of 325, was more effective for patients with previous polyps.

“So we know from these two papers that aspirin is effective in preventing polyps, but we still do not know the best dose,” Sandler said.

Three additional nationwide studies are still underway to see if rofecoxib (Vioxx®) or celecoxib, drugs similar to aspirin but with fewer side effects, can prevent the growth of polyps in people with normal risk. Those studies should be completed by November 2004. Previous studies using drugs, dietary fiber or vitamin supplements to prevent adenomas have not had a significant effect.

Aspirin and these newer drugs inhibit an enzyme known as COX-2 that controls inflammation. COX-2 is expressed early and at high levels in colon tumors, where it leads to increased cell proliferation, increased capacity to invade normal tissue and the stimulation of new blood vessels.

This work was supported by grants from the National Institutes of Health and the National Cancer Institute. The study originated in 1992 in Cancer and Leukemia Group B, a national clinical research group.