Skip to main content
SpringerLink
Log in

The role of aspirin in the prevention of polyp recurrence: What is the right dose?

  • Published:
Current Colorectal Cancer Reports

Abstract

Large cohort studies have demonstrated efficacy of aspirin for cardiovascular disease prevention. Aspirin and other NSAIDs inhibit cyclooxygenase-2 (COX-2), a mediator of prostaglandin production. Nonselective (sulindac) and selective COX-2 inhibitors (celecoxib, rofecoxib) induced regression of adenomas in familial adenomatous polyposis, with dose-dependent efficacy in one such trial. Randomized, controlled trials of patients with previous adenoma or colorectal cancer have shown significant efficacy at daily aspirin doses of 81 to 325 mg/d, although lowest effective aspirin dose was not clearly established. Cohort studies have underscored the need for very long-term (> 10 years) use of aspirin to reduce rates of colorectal cancer. Confounders included intermittent and variable dosing and the use of other NSAIDs and risk modifying drugs, so no clear aspirin dosing message has come from cohort studies. The randomized, controlled trials and cohort studies have taken place during a time when NSAID drug safety has come under challenge. Adverse cardiovascular events in the selective COX-2 inhibitor trials in nonfamilal adenomas have forced reexamination of the safety of NSAIDs in general. New studies will have to balance efficacy and safety more than ever.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Jemal A, Siegel R, Ward E, et al.: Cancer statistics, 2006. CA Cancer J Clin 2006, 56:106–130.

    Article  PubMed  Google Scholar 

  2. Pickhardt PJ, Choi JR, Hwang I, et al.: Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 2003, 349:2191–2200.

    Article  PubMed  CAS  Google Scholar 

  3. Hayden M, Pignone M, Phillips C, et al.: Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002, 136:161–172.

    PubMed  CAS  Google Scholar 

  4. Ridker PM, Cook NR, Lee I-M, et al.: A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med 2005, 352:1293–1304.

    Article  PubMed  CAS  Google Scholar 

  5. Hawk E, Umar A, Viner JL: Colorectal cancer chemoprevention—an overview of the science. Gastroenterology 2004, 126:1423–1447.

    Article  PubMed  Google Scholar 

  6. Barnes CJ, Lee M: Chem oprevention of spontaneous intestinal adenomas in the adenomatous polyposis coli Min mouse model with aspirin. Gastroenterology 1998, 114:873–877.

    Article  PubMed  CAS  Google Scholar 

  7. Reddy BS, Rao CV, Rivenson A, et al.: Inhibitory effect of aspirin on azoxymethane-induced colon carcinogenesis in F344 rats. Carcinogenesis 1993, 14:1493–1497.

    Article  PubMed  CAS  Google Scholar 

  8. Craven PA, DeRubertis FR: Effects of aspirin on 1,2-dimethylhydrazine-induced colonic carcinogenesis. Carcinogenesis 1992, 13:541–546.

    Article  PubMed  CAS  Google Scholar 

  9. Shpitz B, Bomstein Y, Kariv N, et al.: Chemopreventive effect of aspirin on growth of aberrant crypt foci in rats. Int J Colorectal Dis 1998, 13:169–172.

    Article  PubMed  CAS  Google Scholar 

  10. Sheehan KM, Sheahan K, O’Donoghue DP, et al.: The relationship between cyclooxygenase-2 expression and colorectal cancer. JAMA 1999, 282:1254–1257.

    Article  PubMed  CAS  Google Scholar 

  11. Marnett LJ, DuBois RN: COX-2: a target for colon cancer prevention. Annu Rev Pharmacol Toxicol 2002, 42:55–80.

    Article  PubMed  CAS  Google Scholar 

  12. Oshima M, Dinchuk JE, Kargman SL, et al.: Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 1996, 87:803–809.

    Article  PubMed  CAS  Google Scholar 

  13. Sheng H, Shao J, Kirkland SC, et al.: Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. J Clin Invest 1997, 99:2254–2259.

    Article  PubMed  CAS  Google Scholar 

  14. Wolfe MM, Lichtenstein DR, Singh G: Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 1999, 340:1888–1899.

    Article  PubMed  CAS  Google Scholar 

  15. Lehmann JM, Lenhard JM, Oliver BB, et al.: Peroxisome proliferators-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal antiinflammatory drugs. J Biol Chem 1997, 272:3406–3410.

    Article  PubMed  CAS  Google Scholar 

  16. Hsu AL, Ching TT, Wang DS, et al.: The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2. J Biol Chem 2000, 275:11397–11403.

    Article  PubMed  CAS  Google Scholar 

  17. Waskewich C, Blumenthal RD, Li H, et al.: Celecoxib exhibits the greatest potency amongst cyclooxygenase (COX) inhibitors for growth inhibition of COX-2-negative hematopoietic and epithelial cell lines. Cancer Res 2002, 62:2029–2033.

    PubMed  CAS  Google Scholar 

  18. van Stolk R, Stoner G, Hayton WL, et al.: Phase I trial of exisulind (sulindac sulfone, FGN-1) as a chemopreventive agent in patients with familial adenomatous polyposis. Clin Cancer Res 2000, 6:78–89.

    PubMed  Google Scholar 

  19. Labayle D, Fischer D, Viehl P, et al.: Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Gastroenterology 1991, 101:635–639.

    PubMed  CAS  Google Scholar 

  20. Giardiello FM, Hamilton SR, Krush AJ, et al.: Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 1993, 328:1313–1316.

    Article  PubMed  CAS  Google Scholar 

  21. Baron JA, Cole BF, Sandler RS, et al.: A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003, 348:891–899.

    Article  PubMed  CAS  Google Scholar 

  22. Sandler RS, Halabi S, Baron JA, et al.: A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 2003, 348:883–890.

    Article  PubMed  CAS  Google Scholar 

  23. Benamouzig R, Deyra J, Martin A, et al.: Daily solube aspirin and prevention of colorectal adenom a recurrence: one-year results of the APACC trial. Gastroenterology 2003, 125:328–336.

    Article  PubMed  CAS  Google Scholar 

  24. Ladenheim J, Garcia G, Titzer D, et al.: Effect of sulindac on sporadic colonic polyps. Gastroenterology 1995, 108:1083–1087.

    Article  PubMed  CAS  Google Scholar 

  25. Matsuhashi N, Nakajima A, Fukushima Y, et al.: Effects of sulindac on sporadic colorectal adenomatous polyps. Gut 1997, 40:344–349.

    PubMed  CAS  Google Scholar 

  26. Bertagnolli, MM, Eagle, CJ, Zauber, AG, et al.: Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med, 2006, 355:873–884.

    Article  PubMed  CAS  Google Scholar 

  27. Arber N, Eagle CJ, Spicak J, et al.: Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med 2006, 355:885–895.

    Article  PubMed  CAS  Google Scholar 

  28. Baron JA, Sandler RS, Bresalier RS, et al.: A randomized trial of rofecoxib for the chem oprevention of colorectal adenomas. Gastroenterology 2006, In press.

  29. Hallak A, Alon-Baron L, Shamir R, et al.: Rofecoxib reduces polyp recurrence in familial polyposis. Dig Dis Sci 2003, 48:1998–2002.

    Article  PubMed  CAS  Google Scholar 

  30. Steinbach G, Lynch PM, Phillips RK, et al.: The effect celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000, 342:1946–1952.

    Article  PubMed  CAS  Google Scholar 

  31. Benamouzig R, Deyra J, Martin A, et al.: Daily soluble aspirin and prevention of colorectal adenoma a recurrence: four years results of the APACC trial. Gastroenterology 2006, 130(Suppl 2):689.

    Google Scholar 

  32. Chan AT, Giovannucci EL, Meyerhardt J, et al.: Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. JAMA 2005, 294:914–923.

    Article  PubMed  CAS  Google Scholar 

  33. Chan AT, Manson JE, Feskinach D, et al.: Long-term aspirin use and mortality: implications for chemoprevention. Gastroenterology 2006, 130(Supp 2):688.

    Google Scholar 

  34. Giovannucci E, Rimm EB, Stampfer MJ, et al.: Aspirin use and risk for colorectal cancer and adenoma in male health professionals. Ann Int Med 1994, 121:241–246.

    PubMed  CAS  Google Scholar 

  35. Steering Committee of the Physicians’ Health Study: Final report on the aspirin component of the ongoing Physicians’ Health Study. Steering Committee of the Physicians’ Health Study Research Group. N Engl J Med 1989, 321:129–135.

    Article  Google Scholar 

  36. Gann PH, Manson JE, Glynn RJ, et al.: Low-dose aspirin and incidence of colorectal tumors in a randomized trial. J Natl Cancer Inst 1993, 85:1220–1224.

    Article  PubMed  CAS  Google Scholar 

  37. Solomon SD, McMurray JV, Pfeffer MA, et al.: Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005, 352:1071–1080.

    Article  PubMed  CAS  Google Scholar 

  38. Bresalier RS, Sandler RS, Quan H, et al.: Cardiovascular events associated with rofecoxib in a colorectal adenoma a chemoprevention trial. N Engl J Med 2005, 352:1092–1102.

    Article  PubMed  CAS  Google Scholar 

  39. Cruz-Correa, M, Hylind, LM, Romans, et al.: Long-term treatment with sulindac in familial adenomatous polyposis: a prospective cohort study. Gastroenterology 2002, 122:641–645.

    Article  PubMed  CAS  Google Scholar 

  40. Winde G, Gumbinger HG, Kemper F, et al.: The NSAID sulindac reverses rectal adenomas in colectomised patients with familial adenomatous polyposis: clinical results of a dose-finding study on rectal sulindac administration. Int J Colorectal Dis 1993, 8:13–17.

    Article  PubMed  CAS  Google Scholar 

  41. Hippisley-Cox J, Coupland C: Risk of myocardial infarction in patients taking cyclooxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population-based nested case-control analysis. BMJ 2005, 330:1366–1373.

    Article  PubMed  CAS  Google Scholar 

  42. McGettigan P, Henry D: Cardiovascular risk and inhibition of cyclooxygenase. JAMA 2006, 296:1633–1644.

    Article  PubMed  CAS  Google Scholar 

  43. Graham, DJ: Cox-2 inhibitors, other NSAIDs, and cardiovascular risk: the seduction of common sense. JAMA 2006, 296:1653–1656.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastrointestinal Medicine and Nutrition-436, University of Texas M. D. Anderson Cancer Center, P. O. Box 301402, Houston, TX, 77230-1402, USA

    Patrick M. Lynch JD, MD

Authors
  1. Patrick M. Lynch JD, MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrick M. Lynch JD, MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lynch, P.M. The role of aspirin in the prevention of polyp recurrence: What is the right dose?. Curr colorectal cancer rep 3, 24–28 (2007). https://doi.org/10.1007/s11888-007-0012-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11888-007-0012-8

Keywords

Search

Navigation