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Colorectal Cancer Health Center
Evidence of Benefit
Chemoprevention
Nonsteroidal anti-inflammatory drugs
The clinical utility of nonsteroidal anti-inflammatory drugs (NSAIDs) results from their ability to inhibit the activity of cyclooxygenase (COX). COX is important in the transformation of arachidonic acid into prostanoids, prostaglandins, and thromboxane A2. NSAIDs include not only aspirin, first-generation nonselective inhibitors of the two functional isoforms of COX, termed COX-1 and COX-2, but newer second-generation drugs that inhibit primarily COX-2. Normally, COX-1 is expressed in most tissues and primarily plays a housekeeping role, e.g., gastrointestinal mucosal protection and platelet aggregation. COX-2 activity is crucial in stress responses and in mediating and propagating the pain and inflammation that are characteristic of arthritis.[1]
Nonselective COX inhibitors include indomethacin (Indocin); sulindac (Clinoril); piroxicam (Feldene); diflunisal (Dolobid); ibuprofen (Advil, Motrin); ketoprofen (Orudis); naproxen (Naprosyn); and naproxen sodium (Aleve, Anaprox). Selective COX-2 inhibitors include celecoxib (Celebrex), rofecoxib (Vioxx), and valdecoxib (Bextra). Rofecoxib and valdecoxib are no longer marketed because of an associated increased risk of serious cardiovascular events.
Both celecoxib and rofecoxib have been associated with serious cardiovascular events including dose-related death from cardiovascular causes, myocardial infarction, stroke, or heart failure.[2,3,4,5] Four trials that demonstrated this increased risk are summarized in Table 1.
Table 1. Cardiovascular Risks Associated With Celecoxib and Rofecoxib Dose/Drugs
| Authors | Dose/Trial Drug | Risk | Indication |
| [3] | Rofecoxib <25 mg/qd; rofecoxib >25 mg/qd | OR = 1.47 (0.99–2.17) 3 vs. 58 (1.27–10.17) | Nested case-control study all users |
| [5] | Celecoxib 200 mg/qd vs. 400 mg bid | 3.4%; HR = 3.4 (95% CI, 1.4–7.8) | Sporadic adenoma prevention trial (N = 2,035) |
| [4] | Rofecoxib 25 mg/qd | RR = 1.92 (95% CI, 1.19–3.11; P = .008) | Chemoprevention sporadic adenoma |
| [2] | Rofecoxib 25 mg/qd | RR (estimated) = 2.66 (95% CI, 1.03–6.86; P = .04) | Chemoprevention sporadic adenoma median study Rx 7.4 months |
Celecoxib reduces the incidence of adenomas; however, celecoxib does not have a role in reducing the risk of sporadic colorectal cancer (CRC). Its long-term efficacy in preventing CRC has not been shown due to increased risk of cardiovascular events, and because there are other effective ways, such as screening to reduce CRC mortality.[6]
Several, but not all, epidemiological studies have reported a reduction in colon cancer incidence associated with the use of aspirin. Several cohort studies suggest a preventive effect of aspirin. Among a group of more than 600,000 adults enrolled in an American Cancer Society study, mortality in regular users of aspirin was about 40% lower for cancers of the colon and rectum.[7,8] In a study of more than 11,000 men and women in Sweden with rheumatoid arthritis (and presumably ingesting NSAIDs), colon cancer incidence was 37% lower and rectal cancer was 28% lower than predicted from cancer registry data.[9] In a report from the Health Professionals Follow-up Study of 47,000 males, regular use of aspirin (at least 2 times per week) was associated with a 30% overall reduction in CRC, including a 50% reduction in advanced cases.[10] In a Women's Health Study randomized 2 x 2 factorial trial of 100 mg of aspirin every other day for an average of 10 years, similar rates of breast, colorectal, or other site-specific cancers were observed in both the aspirin and placebo arms.[11] In a report from the Nurses’ Health Study involving 82,911 women followed for 20 years, the multivariate RR for colon cancer was 0.77 (95% CI, 0.67–0.88) among women who regularly used aspirin (=2 standard 325 mg tablets per week) compared with nonregular use. Significant RR was not observed, however, until more than 10 years of use. The benefit appeared to be dose-related (e.g., women who used more than 14 aspirin per week for longer than 10 years had a multivariate RR for cancer of 0.47 [95% CI, 0.31–0.71]). A similar dose-response relationship was observed for nonaspirin NSAIDs. The incidence of reported major gastrointestinal bleeding events also appeared to be dose-related.[12] A population-based retrospective cohort study of nonaspirin NSAID use among individuals aged 65 years and older was also associated with lower risk, particularly with increasing durations of use.[13] In the Physicians’ Health Study, 22,000 men aged 40 to 84 years were randomly assigned to receive placebo or aspirin (325 mg every other day) for 5 years. There was no reduction in invasive cancers or adenomas at a median follow-up of 4.5 years.[14] In a subsequent analysis of more than 12 years, both randomized and observational analyses indicated that there was no association between the use of aspirin and the incidence of CRC. The low dose of aspirin and the short treatment period may account for the null findings.[15]
WebMD Public Information from the National Cancer Institute
This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER
In addition to taking drugs that combat nausea during chemotherapy treatments, there are simple things patients can do.
