Can over-the-counter drugs help prevent colorectal cancer?

By Naveed Saleh, MD, MS, for MDLinx
Published December 20, 2018

Key Takeaways

When taken as chemoprevention for colorectal cancer, neither aspirin nor omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) decreased the number of people manifesting at least one polyp, according to the results of a recent study published in The Lancet.

“EPA and aspirin both have proof of concept for colorectal cancer chemoprevention, aligned with an excellent safety profile,” wrote authors, led by Mark Hull, PhD, clinician scientist and consultant gastroenterologist, Institute of Biomedical and Clinical Sciences, University of Leeds, St James’s University Hospital, Leeds, UK. “Therefore, we aimed to test the efficacy of EPA and aspirin, alone and in combination and compared with a placebo, in individuals with sporadic colorectal neoplasia detected at colonoscopy.”

Results from previous randomized-controlled trials have indicated that aspirin and metformin reduced the risk of colorectal adenomas after 1 year of chemoprevention.

In a 2×2 factorial, randomized, controlled trial, researchers randomized 640 patients aged between 55 and 73 years (mean age: 65 years; 80% men) at high-risk of colorectal cancer per screening endoscopy to one of four groups: 2 g EPA-free fatty acid (EPA-FFA) daily, 300 mg aspirin daily, EPA-FFE plus aspirin, or placebo. The primary outcome was adenoma detection rate (ADR)—the proportion of patients with any adenoma—at colonoscopy after 1 year of treatment.

Dr. Hull and his team found the following ADRs: 63% in the EPA group, 61% in the aspirin group, 61% in the EPA-plus-aspirin group, and 61% in the placebo group. They observed no effect for EPA or aspirin.

These drugs were well tolerated, with six gastrointestinal bleeds documented: two in the EPA group, three in the aspirin group, and one in the placebo group.

With respect to secondary analysis, the investigators did find support for chemopreventive activity of both EPA and aspirin. EPA and aspirin expressed both subtype- and site-selective effects: Aspirin was effective at reducing the total number of conventional adenomas in the left colorectum, and EPA was effective at reducing the total number of conventional (particularly serrated adenomas) in the right colorectum.

The study attained only 83% of its recruitment target due mostly to high screening failure, which included an unexpectedly high number of individuals who did not consent to the study after initial screening. According to the authors, this finding raises concern for the desirability of chemoprevention among patients—even in patients at high-risk for colorectal carcinoma.

Dr. Hull and colleagues also noted that their results may lead to questions as to whether ADR or adenoma number is the prime measure of chemoprevention efficacy.

“The trial raises the crucial question of whether ADR or adenoma number is the best measure of chemoprevention efficacy in polyp prevention trials that are based on quality-assured colonoscopy in individuals at high risk of colorectal cancer, in which the ADR is used as a performance indicator, and the adenoma recurrence rate is high,” they wrote.

“Neither EPA nor aspirin treatment were associated with a reduction in the proportion of patients with at least one colorectal adenoma. Further research is needed regarding the effect on colorectal adenoma number according to adenoma type and location,” concluded the authors. “Optimal use of EPA and aspirin might need a precision medicine approach to adenoma recurrence.”

This study was funded by the Efficacy and Mechanism Evaluation Programme, a UK Medical Research Council and National Institute for Health Research partnership.

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