Colorectal cancer NSAIDs

Approximately 8% to 20% of patients with UC and 7% to 26% of patients with CD are elderly at initial diagnosis.42 In general, IBD presents similarly in elderly patients compared to younger individuals. Elderly patients may have more comor-bid diseases, some of which may make the diagnosis of IBD more difficult. Such conditions include ischemic colitis, diverticular disease, and microscopic colitis. Increased age is also associated with a higher incidence of adenomatous polyps, but the onset of IBD at an advanced age does not appear to increase the risk of developing colorectal cancer. Elderly patients may also use more medications, particularly NSAIDs, which may induce or exacerbate colitis. 

In summary, the true association between most dietary factors and the risk of colon cancer is unclear. The protective effects of fiber, calcium, and a diet low in fat are not completely known. Lifestyle factors such as NSAID use and hormone use appear to decrease the risk of colorectal cancer, whereas physical inactivity, alcohol use, and smoking appear to increase the risk of colon cancer. Clinical risk factors and genetic mutations are well-known risks for colon cancer. 

Selective COX-2 inhibitors have also been shown to prevent early and late forms of colorectal neoplasia in rat models. Reddy et al. showed that administration of celecoxib inhibited aberrant colonic crypt foci (ACF) induction and multiplicity by about 40-49% in an azoxymethane-induced ACF rat model (81). Later the same investigators also showed that dietary administration of celecoxib can inhibit both the incidence and multiplicity of colon tumors by about 93 % and 97 %, respectively in the same rat model (82). Other researchers reported similar results with the Min mouse model (52). There is little data on human clinical trials with selective COX-2 inhibitors for colorectal tumor prevention. Recently Steinbach et al. conducted a double-blind, placebo-controlled study with 77 patients with FAP, and reported that treatment with celecoxib, a selective COX-2 inhibitor, for 6 mo led to a significant reduction (28%) in the number of colorectal polyps in these patients (50). Collectively, COX-2 nonspecific or specific NSAIDs appear to have chemopreventive activity against colorectal cancer development. Selective... 

Kune GA. Colorectal cancer chemoprevention aspirin, other NSAID and COX-2 inhibitors. Aust NZ JSurg 2000 70 452 155. 

Celecoxib has been approved for the treatment of osteoarthritis and rheumatoid arthritis, and rofecoxib has been approved for the treatment of osteoarthritis, acute pain and primary dysmenorrhea. Celecoxib and rofecoxib do not appear to differ in efficacy for the treatment of osteoarthritis. However, neither drug has efficacy greater than that of the non-selective NSAIDs. Since the COX-2 enzyme appears to play an important role in colon cancer the COX-2 inhibitors may find future uses in the treatment or prevention of colorectal cancer. 

Chell S, Patsos HA, Qualtrough D, et al. Prospects in NSAID-derived chemoprevention of colorectal cancer. Biochem Soc Trans. 2005 33 667-671. 

Waterhouse DM, Brenner D. Aspirin, NSAIDs, and risk reduction of colorectal cancer. The problem is translation. Arch Intern Med 1994 154(4) 366-8. 

Despite these complexities, COX-2-specific inhibitors relieve pain in many OA patients with a lower risk of GI adverse events than nonspecific NSAIDs. COX-2 inhibitors, members of the coxib class newly created by the World Health Organization, have become extremely widely used over a short period of time. These agents continue to be studied intensely not only for their efficacy and toxicity profile in rheumatic disease, but also for exciting potential applications such as the prevention of Alzheimer s disease and colorectal cancer. 

Nonsteroidal Anti-Inflammatory Drugs (NSAID) and Colorectal Cancer... 

---