Update on Prostate Cancer Chemoprevention

Nonsteroidal Antiinflammatory Drugs

Nonsteroidal antiinflammatory drugs act to prevent the synthesis of endogenous prostaglandins by inhibition of the cyclooxygenase (COX) enzyme. Expression of the COX-2 isoenzyme is 3–5 times greater in patients with prostate cancer than in those with benign prostatic hyperplasia and is responsible for increased angiogenesis, tumorigenesis, and prostate cancer growth.^[31,32,33]

In a case-control study, daily use of over-the-counter NSAIDs was associated with a lower risk of prostate cancer (OR 0.34, 95% CI 0.23–0.58, p < 0.01), as was use of prescription NSAIDs (OR 0.35, 95% CI 0.15–0.84, p < 0.05).^[34] Another study was unable to show a relationship between aspirin therapy and reduced prostate cancer risk.^[35] A meta-analysis of the combined results from 12 studies of NSAIDs and prostate cancer risk found a 10% risk reduction associated with aspirin therapy (OR 0.9, 95% CI 0.82–0.99).^[36] However, the risk associated with other NSAIDs was more variable (OR 0.87, 95% CI 0.61–1.23). In another critical review of the literature regarding NSAIDs and the risk of several cancers, the authors combined the results from seven cohort and seven case-control studies regarding prostate cancer.^[37] They found an association between regular intake of NSAIDs and reduced prostate cancer risk (RR 0.61, 95% CI 0.45–0.85).

Studies have evaluated aspirin and nonselective NSAIDs. Because overexpression of COX-2 in the prostate is associated with increased angiogenesis and prostate cancer cell growth, two large randomized controlled trials with selective COX-2 inhibitors have been started. Given the recent evidence regarding increased cardiovascular risk with selective COX-2 inhibitors, it is unclear whether these trials will continue or if administration of these agents can be justified.^[38]

Pharmacotherapy. 2006;26(3):353-359. © 2006  Pharmacotherapy Publications