[EMBARGOED UNTIL 5:00 P.M. Eastern March 5 to coincide with publication in the New England Journal of Medicine on March 6, 2003.]
ASPIRIN PREVENTS POLYPS IN COLON CANCER PATIENTS
COLUMBUS, Ohio - A single tablet of aspirin a day may be one of the best ways to prevent colorectal polyps from recurring in patients who have already had colon cancer, a new study has shown.
The finding comes from a large, randomized, double-blind trial in which the benefits from the aspirin were so striking that the study was stopped midway through the investigation so that patients receiving a placebo could take the medication instead.
The study found there were 37 percent fewer patients who developed adenomas – a precursor to colon cancer – among those taking a standard daily dose of aspirin, compared to patients who did not.
The study, initially conducted under the auspices of National Cancer Institute’s Cancer and Leukemia Group B (CALGB), a consortium of clinical trials centers, involved 719 patients with a history of colon cancer at three dozen participating institutions from 1993-2000.
“While other research has shown that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the risk of colon cancer in large populations, this is among the first to demonstrate in a scientific manner the protective properties of aspirin in people who have already had the disease,” says Electra Paskett, chair of the CALGB committee that provided oversight to the study and associate director of population sciences at The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.
Paskett, chair of the CALGB’s Cancer Control and Health Outcomes Committee and a co-author of the study, says the implications of the results are important because colorectal cancer is the second most common malignancy when male and female cancers are considered together.
The findings are reported in the March 6 issue of The New England Journal of Medicine.
“Aspirin and other NSAIDs have consistently demonstrated possible protection against colon cancer and other diseases,” says Robert Sandler, professor of medicine and epidemiology and chief of the division of digestive diseases and nutrition at the University of North Carolina at Chapel Hill and lead principal investigator of the project.
"But this study offers the strongest proof of protection because participants were assigned at random to the two study arms; in other words, this was a true experiment.”
Colorectal adenomas are widely viewed as the precursor to most colon cancer, so investigators hypothesized if they could prevent the occurrence of polyps, they could slow or block cancer from recurring in patients who had already been treated for it.
Study participants were between the ages of 30 and 80, and all had been treated for colon or rectal cancer but were believed to be at low risk for recurrence. Researchers first screened the participants to make sure it was safe for them to take the aspirin every day, and monitored them for their motivation and adherence to the dosing schedule. Following the initial three-month evaluation period, 635 patients were randomly assigned to either the aspirin or placebo group.
The patients remained under the care of their regular physicians, and investigators monitored the findings of their colonoscopies or sigmoidoscopies, examinations periodically conducted during routine follow-up care for colon cancer patients.
Researchers measured the proportion of patients in each group who developed polyps, the size and extent of the polyps and how long it took from randomization for the polyps to first appear.
Statistics revealed that 517 patients had at least one colonoscopy a little over a year after randomization; 17 percent of patients in the aspirin group had developed one or more adenomatous polyps compared with 27 percent of those in the placebo group. The aspirin also decreased the number of adenomas each patient developed and prolonged the time to their initial appearance. These findings held true even after controlling for age, sex, cancer stage, the number of colonoscopies and the time to the initial colonoscopy.
On the other hand, the median size of the largest polyp was similar in the two groups, as was the proportion of participants who developed large or advanced polyps. The number and types of adverse events – everything from stroke and ulcers to gastrointestinal bleeding and death – were also similar between the two arms of the study.
The study was halted when an independent data and safety monitoring board found the statistics about the benefits of aspirin so compelling, it felt that patients in the placebo arm should be free to choose to take the medication.
The research team chose a dose level of 325 mg of aspirin because that is the standard dose in which aspirin comes. The study did not determine whether a lower dose would be just as effective, or if a higher dose would work even better. They also acknowledge that aspirin, by itself, should not take the place of routine surveillance for recurrence of polyps through regular colonoscopy examination because it can cause side effects in some people and did not completely block polyps from forming.
Sandler acknowledges Journal readers may be perplexed by a companion study in the same issue that found that a smaller dose of aspirin (81 mg) protected people with a history of polyps from recurrence, but that a larger dose (325 mg – the same used in the CALGB study) did not appear to offer any benefit.
“We studied two different populations. It is difficult to completely reconcile these seemingly contradictor results. I would simply conclude that the two studies provide strong evidence that aspirin is protective and less guidance about the best dose,” Sandler says.
“The good news is that both studies tell us that sometimes, the best chemopreventive agents are close at hand, and relatively inexpensive,” says Paskett.
Contact: Michelle Gailiun, Medical Center Communications,
614-293-3737, or Gailiun.email@example.com