Nnsteroidal Ati Inflammatory gents for Colon Cancer Prevention

Colon cancer prevention has now focused on novel targeted therapies, such as non-steroidal anti-inflammatory agents (NSAIDs). Aspirin, an inhibitor of COX-1 and -2, has been studied in several large randomised studies, but the effect on colorectal cancer prevention is unclear. The US Physician's Health Study, which enrolled 22 071 physicians as participants, reported that aspirin had no effect on the incidence of polyps or colon cancer [3]. However, Baron et al. conducted the Aspirin/Folate Polyp Prevention Study, a randomised, double-blind, placebo-controlled trial of daily aspirin (325 mg and 8 mg) and daily folate (1 mg) in 1121 patients with a recent history of colon adenomas [4]. This trial demonstrated that the 81-mg dose of aspirin prevented recurrence of colorectal adenomas (47% placebo vs. 38% aspirin 81 mg vs. 45% aspirin 325 mg; p=0.04). This translated into a relative-risk reduction of 19% in the 81-mg aspirin group and a non-significant reduction of 4% in the 325-mg aspirin group. This study also reported a relative-risk reduction of 40% in the 81-mg aspirin group for advanced lesions. In addition, Sandler et al. [5] reported on the Colorectal Adenoma Prevention Study, which randomised 635 patients with prior colorectal cancer to 325-mg aspirin or placebo. Twenty percent of the placebo group developed recurrent adenomas compared with 17% in the aspirin arm (p=0.0004), for an adjusted relative risk of 0.65. Aspirin intervention delayed the development of recurrent adenoma and also decreased the number of recurrent adenomas.

Although the role of aspirin remains debated, the benefit of NSAIDs in chemoprevention has clearly been defined in certain high-risk subgroups [6]. In clinical trials of patients with FAP, sulindac (150 mg twice a day for 9 months) was shown to decrease the number of polyps by 44% and decrease the diameter of the polyps by 35% (p=0.014 and p<0.001, respectively) [7]. In a study, 77 patients with FAP (more than 5 polyps 2 mm in size) were randomised to receive placebo, 100 mg, or 400 mg of celecoxib twice daily [8]. Celecoxib is a selective COX-2 inhibitor. Response to treatment was reported as the mean percent change from baseline. After 6 months, the 30 patients assigned to 400 mg of celecoxib had a 28% reduction in the mean number of colorectal polyps (p=0.003) and a 30.7% reduction in the polyp burden (p=0.001) compared with 4.5 and 4.9% in the placebo group, respectively. This positive result led to the FDAs approval of celecoxib in the treatment of patients with FAP.

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