Japanese researchers reported on 1 April 2021 in The Lancet Gastroenterology & Hepatology findings from a randomised, double-blind, placebo-controlled study with a two-by-two factorial design, conducted in 11 centres, that low-dose aspirin safely suppressed the recurrence of colorectal polyps larger than 5 mm in patients with familial adenomatous polyposis (FAP).
They reported in the study background that the only established treatment for preventing colorectal cancer in patients with FAP is colectomy. However, colectomy reduces patient quality of life.
In this study, eligible patients were aged 16 to 70 years with a history of more than 100 adenomatous polyps in the large intestine and without prior colectomy. Before the study, patients underwent endoscopic removal of all colorectal polyps of at least 5 mm in diameter.
Randomisation was done with a minimisation method with a random component to balance the groups with respect to the adjustment factors of sex, age (<30 years vs ≥30 years), or smoking status. Patients and researchers were masked to the treatment group.
There were four study groups: aspirin (100 mg per day) plus mesalazine (2 g per day), aspirin (100 mg per day) plus mesalazine placebo, aspirin placebo plus mesalazine (2 g per day), or aspirin placebo plus mesalazine placebo. Treatment was continued until 1 week before 8 month colonoscopy.
The primary endpoint was the incidence of colorectal polyps of at least 5 mm at 8 months and was assessed in the intention-to-treat (ITT) population. Safety was assessed in the ITT population. The study team also performed a per-protocol analysis including only patients who took at least 70% of the allocated study drug.
In total, 104 patients were randomly assigned to receive either aspirin or aspirin placebo (n=52) or mesalazine or mesalazine placebo (n=52). Two patients withdrew from the aspirin plus mesalazine placebo group.
In total, 26 (50%) of 52 patients who received no aspirin had colorectal polyps of at least 5 mm at 8 months, 15 (30%) of the 50 patients who received any aspirin, 21 (42%) of the 50 patients who received no mesalazine, and 20 (38%) of the 52 patients who received any mesalazine.
The adjusted odds ratio for polyp recurrence was 0.37 (95% confidence interval [CI] 0.16–0.86) in the patients who received any aspirin and 0.87 (95% CI 0.38–2.00) in any who received mesalazine.
The most common adverse events were grade 1–2 upper gastrointestinal symptoms in three (12%) of 26 patients who received aspirin plus mesalazine, one (4%) of 24 patients who received aspirin plus mesalazine placebo, and one (4%) of 26 patients who received mesalazine plus aspirin placebo. There was one grade 4 event in the mesalazine plus aspirin placebo group, but not related to the treatment.
The authors concluded that that their results suggest an effect of low-dose aspirin for FAP and it could be an alternative for preventing colorectal cancer in these patients.
In an accompanied editorial, Patrick Lynch of the Department of Gastroenterology, Hepatology & Nutrition, University of Texas MD Anderson Cancer Center in Houston, TX, US wrote that the key issues in colorectal adenoma chemoprevention revolve around drug efficacy and safety. In pre-colectomy and post-colectomy patients, the goal of chemoprevention is to prevent or slow the growth of adenomas, thereby attenuating risk of cancer and thus reducing the need for or delay surgery and also potentially decreasing the frequency of surveillance endoscopy.
The study was funded by the Japan Agency for Medical Research and Development.
- Ishikawa H, Mutoh M, Sato Y, et al. Chemoprevention with low-dose aspirin, mesalazine, or both in patients with familial adenomatous polyposis without previous colectomy (J-FAPP Study IV): a multicentre, double-blind, randomised, two-by-two factorial design trial. The Lancet Gastroenterology & Hepatology; Published online 1 April 2021. DOI: https://doi.org/10.1016/S2468-1253(21)00018-2
- Lynch PM. Low-dose aspirin and mesalazine for patients with familial adenomatous polyposis. The Lancet Gastroenterology & Hepatology; Published online 1 April 2021. DOI: https://doi.org/10.1016/S2468-1253(21)00102-3