Colon cancer chemoprevention: Clinical development of aspirin as a chemopreventive agent

✍ Scribed by Krishnan, Koyamangalath; Ruffin, Mack T.; Brenner, Dean E.

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 81 KB
• Volume: 67
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(1997)28/29+<148::aid-jcb18>3.0.co;2-d

✦ Synopsis

We have studied aspirin as a potential chemopreventive for colorectal cancer, completing Phase I studies on aspirin pharmacology and potential biomarker assays (prostaglandins, PGE 2 and PGF 2␣ and cyclooxygenase modulation) in normal human subjects. These studies have determined the optimal dose of aspirin for future Phase IIa and IIb chemopreventive trials in high-risk cohorts of patients for colon cancer. Aspirin's effects on rectal prostaglandins are prolonged, detectable even after aspirin and its metabolite are removed from the plasma. Aspirin-mediated inhibition of prostaglandin production in the human rectal epithelium may be related to direct suppression of cyclooxygenase transcription and not to enzyme inactivation by acetylation. A systematic method to monitor adherence (self-report, telephone contact, pill count, and microelectronic monitoring) has been established for future trials. Strategies to improve recruitment of high-risk cohorts have been developed. Phase IIa non-randomized studies with aspirin at 81 mg in high-risk cohorts (resected Duke's A colon cancer, Duke's C colon cancer treated with adjuvant therapy and disease-free at 5 years, history of colon adenomas Ͼ 1 cm, two or more first-degree relatives with colon cancer, and familial adenomatous polyposis and hereditary non-polyposis colorectal cancer syndromes) are currently being conducted for surrogate end-point biomarker (prostaglandins, cyclooxygenase, cellular mucins, and proliferation) modulation.