PURPOSE
A systematic review was conducted to determine the effect of nonsteroidal anti-inflammatory drugs for the prevention or regression of colorectal adenomas and cancer.
METHODS
Randomized, controlled trials through September 2003 were identified. Nonsteroidal anti-inflammatory drugs were the interventions. The primary outcomes were the number of patients with at least one colorectal adenoma, a change in polyp burden, or colorectal cancer. The secondary outcome was adverse events. Two reviewers independently extracted data and assessed trial quality. Dichotomous outcomes were reported as relative risks with 95 percent confidence intervals. The data were combined if clinically and statistically reasonable.
RESULTS
Nine trials with 150 familial adenomatous polyposis and 24,143 population patients met the inclusion criteria. The interventions included sulindac, celecoxib, or aspirin. From the combined results of three trials, significantly fewer patients in the aspirin group developed recurrent sporadic colorectal adenomas (relative risk, 0.77 (95 percent confidence interval, 0.61, 0.96), number needed to treat 12.5 (95 percent confidence interval, 7.7, 25)) after one to three years. In another three trials, patients with familial adenomatous polyposis who received nonsteroidal anti-inflammatory drugs had a greater proportional reduction (range, 11.9–44 percent) in the number of colorectal adenomas compared with those in the control group (range, 4.5–10 percent). There was no significant difference for the outcomes of colorectal cancer or adverse events in any of the trials.
CONCLUSIONS
There is combined evidence from three randomized trials that aspirin significantly reduced the recurrence of sporadic adenomatous polyps. There was evidence from short-term trials to support regression, but not elimination or prevention, of colorectal polyps in familial adenomatous polyposis.
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REFERENCES
Canadian Cancer Society. Canadian Cancer Statistics, 2002. Available at: http://www.cancer.ca. Accessed February 2003.
American Cancer Society. Cancer Facts & Figures. Available at: http://www.cancer.org. Accessed February 2003.
Trends in screening for colorectal cancer: United States, 1997 and 1999. MMWR 2001;50:162–6
SW Vernon (1997) ArticleTitleParticipation in colorectal cancer screening: a review J Natl Cancer Inst 89 1406–22
N Arber ParticleDo (2000) ArticleTitleNSAIDs prevent colorectal cancer Can J Gastroenterol 14 299–307
E Hawk R Lubet P Limburg (1999) ArticleTitleChemoprevention in hereditary colorectal cancer syndromes Cancer 86 1731–43
A Paganini-Hill (1994) ArticleTitleAspirin and the prevention of colorectal cancer: a review of the evidence Semin Surg Oncol 10 158–64
D Turner HJ Berkel (1993) ArticleTitleNonsteroidal anti-inflammatory drugs for the prevention of colon cancer Can Med Assoc J 149 595–602
H Vainio G Morgan P Kleihues (1997) ArticleTitleAn international evaluation of the cancer-preventive potential of nonsteroidal anti-inflammatory drugs Cancer Epidemiol Biomarkers Prev 6 749–53
E Giovannucci EB Rimm MJ Stampfer GA Colditz A Ascherio WC Willett (1994) ArticleTitleAspirin use and the risk for colorectal cancer and adenoma in male health professionals Ann Intern Med 121 241–6
E Giovannucci KM Egan DJ Hunter et al. (1995) ArticleTitleAspirin and the risk of colorectal cancer in women N Engl J Med 333 609–14
AJ Dannenberg D Zakim (1999) ArticleTitleChemoprevention of colorectal cancer through inhibition of cyclooxygenase-2 Semin Oncol 26 499–504
RA Gupta RN Dubois (2000) ArticleTitleTranslational studies on Cox-2 inhibitors in the prevention and treatment of colon cancer Ann Acad Sci 910 196–206
Clarke M, Oxman AD. Cochrane reviewers’ handbook 4.1.6
National Cancer Institute. Common toxicity criteria. Available at: http://ctep.cancer.gov/reporting/ctc.html. Accessed May 12, 2003.
F Seow-Choen G Pappalardo G Maiani (1996) ArticleTitleProspective randomized study of sulindac versus calcium and calciferol for upper gastrointestinal polyps in familial adenomatous polyposis Br J Surgery 83 1763–6
KP Nugent KC Farmer AD Spigelman CB Williams RK Phillips (1993) ArticleTitleRandomized controlled trial of the effect of sulindac on duodenal and rectal polyposis and cell proliferation in patients with familial adenomatous polyposis Br J Surg 80 1618–9
J Burns PD Chapman J Mathers et al. (1995) ArticleTitleThe protocol for a European double-blind trial of aspirin and resistant starch in familial adenomatous polyposis: the CAPP study Concerted Action Polyposis Prevention. Eur J Cancer 31A 1385–6
J Burns PD Chapman J Mathers DT Bishop H Lynch (1997) ArticleTitleCAPP2: an international controlled trial of aspirin and resistant starch in carriers of HNPCC J Med Genet 34 S53
Anonymous. Design of the Women’s Health Initiative clinical trial and observational study. The Women’s Health Initiative Study Group. Control Clin Trials 1998;19:61–109.
IM Lee NR Cook JE Manson JE Buring CH Hennekens (1999) ArticleTitleB-Carotene supplementation and incidence of cancer and cardiovascular disease: the Women’s Health Study J Natl Cancer Inst 91 2102–6
InstitutionalAuthorNameThe steering committee of the Physicians’ Health Group (1988) ArticleTitlePreliminary report: findings from the aspirin component of the ongoing physicians’ health study N Engl J Med 318 263–4
R Benamouzig H Yoon J Little et al. (2001) ArticleTitleAPACC, a French prospective study on aspirin efficacy in reducing colorectal adenoma recurrence: design and baseline findings Eur J Cancer Prev 10 327–35
PH Gann JE Manson RJ Glynn JE Buring CH Hennekens (1993) ArticleTitleLow-dose aspirin and incidence of colorectal tumors in a randomized trial J Natl Cancer Inst 85 1220–4
FM Giardiello VW Yang LM Hylind et al. (2002) ArticleTitlePrimary chemoprevention of familial adenomatous polyposis with sulindac N Engl J Med 346 1054–9
R Benamouzig J Deyra A Martin et al. (2003) ArticleTitleDaily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial Gastroenterology 125 328–36
JA Baron BF Cole RS Sandler et al. (2003) ArticleTitleA randomized trial of aspirin to prevent colorectal adenomas N Engl J Med 348 891–9
RS Sandler S Halabi JA Baron et al. (2003) ArticleTitleA randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer N Engl J Med 348 883–90
J Ladenheim G Garcia D Titzer et al. (1995) ArticleTitleEffect of sulindac on sporadic colonic polyps Gastroenterology 108 1083–7
G Steinbach PM Lynch RK Phillips et al. (2000) ArticleTitleThe effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis N Engl J Med 342 1946–52
FM Giardiello SR Hamilton AJ Krush et al. (1993) ArticleTitleTreatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis N Engl J Med 328 1313–6
D Labayle D Fischer P Vielh et al. (1991) ArticleTitleSulindac causes regression of rectal polyps in familial adenomatous polyposis Gastroenterology 101 635–9
SJ Winawer AG Zauber MN Ho (1993) ArticleTitlePrevention of colorectal cancer by colonoscopic polypectomy N Engl J Med 329 1977–81
SJ Winawer (1999) ArticleTitleNatural history of colorectal cancer Am J Med 106 3S–6S
A multi-centre double blind randomised controlled trial of aspirin and/or folate supplementation for the prevention of recurrent colorectal adenomas. UKCCCR National Register of Cancer Trials Web site. Available at: http://www.ctu.mrc.ac.uk/ukcccr/home.asp. Accessed October 30, 2003.
Trial update and news. Available at: http://www.ncl.ac.uk/capp/ptrial.htm. Accessed October 30, 2003.
KM Rexrode IM Lee NR Cook CH Hennekens JE Buring (2000) ArticleTitleBaseline characteristics of participants in the Women’s Health Study J Womens Health 9 19–27
InstitutionalAuthorNameU.S. Preventive Task Force (2002) ArticleTitleAspirin for the primary prevention of cardiovascular events: recommendations and rationale Ann Intern Med 136 161–72
D Mukherjee SE Nissen EJ Topol (2001) ArticleTitleRisk of cardiovascular events associated with selective COX-2 inhibitors JAMA 286 954–9
S Suleiman DK Rex A Sonnenberg (2002) ArticleTitleChemoprevention of colorectal cancer by aspirin: a cost-effectiveness analysis Gastroenterology 122 78–84
U Ladabaum CL Chopra G Huanga JM Scheiman ME Chernew AM Fendrick (2001) ArticleTitleAspirin as an adjunct to screening for prevention of sporadic colorectal cancer: a cost-effectiveness analysis Ann Intern Med 135 769–81
M Cruz-Correa LM Hylinda KE Romans SV Booker FM Giardiello (2002) ArticleTitleLong-term treatment with sulindac in familial adenomatous polyposis: a prospective cohort study Gastroenterology 122 641–5
Y Niv GM Fraser (1994) ArticleTitleAdenocarcinoma in the rectal segment in familial polyposis coli is not prevented by sulindac therapy Gastroenterology 107 854–7
AG Thorson HT Lynch TC Smyrk (1994) ArticleTitleRectal cancer in FAP patient after sulindac Lancet 343 180
JJ Keller GJ Offerhaus P Drillenburg et al. (2001) ArticleTitleMolecular analysis of sulindac-resistant adenomas in familial adenomatous polyposis Clin Cancer Res 7 4000–7
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T. K. Asano is a research fellow of the National Cancer Institute of Canada, with funds provided by the Canadian Cancer Society.
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Asano, T., McLeod, R. Nonsteroidal Anti-inflammatory Drugs and Aspirin for the Prevention of Colorectal Adenomas and Cancer: A Systematic Review. Dis Colon Rectum 47, 665–673 (2004). https://doi.org/10.1007/s10350-003-0111-9
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DOI: https://doi.org/10.1007/s10350-003-0111-9