Genetics of Colorectal Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Major Genetic Syndromes
Table 9. Practice Guidelines for Diagnosis and Colon Surveillance of Lynch Syndrome continued...
Chemoprevention in LS
The Colorectal Adenoma/Carcinoma Prevention Programme (CAPP2) was a double-blind, placebo-controlled, randomized trial to determine the role of aspirin in preventing CRC in patients with LS who were in surveillance programs at a number of international centers. The study randomly assigned 861 participants to aspirin (600 mg/day), aspirin placebo, resistant starch (30 g/day), or starch placebo for up to 4 years. At a mean follow-up of 55.7 months (range: 1–128 mo), 53 primary CRCs developed in 48 participants (18 of 427 in the aspirin group and 30 of 434 in the aspirin placebo group). Seventy-six patients who refused randomization to the aspirin groups (because of an aspirin sensitivity or a history of peptic ulcer disease) were randomly assigned to receive resistant starch or resistant starch placebo. The intention-to-treat analysis yielded an HR for CRC of 0.63 (95% CI, 0.35–1.13; P = .12). However, five of the patients who developed CRC developed two primary colon cancers. A Poisson regression was performed to account for the effect of the multiple primary CRCs and yielded a protective effect for aspirin (incidence rate ratio [IRR], 0.56; 95% CI, 0.32–0.99; P = .05). For participants who completed at least 2 years of treatment, the per-protocol analysis yielded an HR of 0.41 (95% CI, 0.19–0.86; P = .02) and an IRR of 0.37 (0.18–0.78; P = .008). An analysis of all LS cancers (endometrial, ovarian, pancreatic, small bowel, gall bladder, ureter, stomach, kidney, and brain) revealed a protective effect of aspirin versus placebo (HR, 0.65; 95% CI, 0.42–1.00; P = .05). There were no significant differences in adverse events between the aspirin and placebo groups, and no serious adverse effects were noted with any treatment. The authors concluded that 600 mg of aspirin per day for a mean of 25 months substantially reduced cancer incidence in LS patients. A limitation of the trial is that the frequency of surveillance studies at the various centers was not reported as being standardized. Earlier CAPP2 trial results for 746 LS patients enrolled in the study were published in 2008  and failed to show a significant preventive effect on incident colonic adenomas or carcinomas (relative risk [RR], 1.0; 95% CI, 0.7–1.4) with a shorter mean follow-up of 29 months (range: 7–74 mo). The CAPP3 trial, which will evaluate the effect of lower doses of aspirin, is expected to begin in 2013.