Nonsteroidal Anti-inflammatory Drugs for Prevention of Colorectal Neoplasms: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

WANG Yiping , PAN Tao , YANG Jinlin , WANG Qiong , GAN Tao

Department of Gasroenterology; West China Hospital of Sichuan University（Chengdu610041）;

Corresponding author：

Keywords：

Nonste roidal anti-inflammatory drugs; Aspirin; Cheomprevention; Colorectal neoplasia; Randomized controlled trials; Systematic review

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Objective 　To assess the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) for the prevention of colorectal neoplasia.
Methods 　A systematic review of all relevant randomized controlled trials and quasi-randomized controlled trials of NSAIDs for prevention of colorectal neoplasms was performed by using The Cochrane Collaboration recommended methods.
Results 　Nine trials were included and assessed. There was sufficient evidence for aspirin to prevent the development of colorectal adenomas compared with placebo in three trials of high quality and large sample size with relative risk (RR) 0.81, 95% confidence interval (CI) 0.72 to 0.91 and P=0.000 5 . No adequate evidence supported aspirin in the prevention of development of colorectal cancer (RR 0.97, 95% CI 0.79 to 1.20, P= 0.79). However, there was no evidence to support sulindac and celecoxib curing or preventing colorectal adenomas or familial adenomatous polyposis (RR 0.71, 95% CI 0.49 to 1.03, P= 0.07 and RR 0.90, 95% CI 0.76 to 1.07, P=0.23). No evidence on the dose of NSAIDs was used for prevention of colorectal adenomas at present. No significant difference was seen in the number of adverse events between patients taking NSAIDs and those taking placebo (P=0.9).
Conclusions 　Aspirin may prevent the development of colorectal adenomas and may avoid polypectomy for 1 in every 10 to 18 persons but we don’t know whether aspirin can be substituted for endoscopically removed colorectal polyps. However, the true clinical benefit for prevention of colorectal neoplasia of NSAIDs should be considered.

Citation： WANG Yiping,PAN Tao,YANG Jinlin,WANG Qiong,GAN Tao. Nonsteroidal Anti-inflammatory Drugs for Prevention of Colorectal Neoplasms: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2005, 05(6): 438-443. doi: Copy

1.	［1］Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL. Genetic alterations during colorectal-tumor development[J]. N Engl J Med, 1988; 319 (9): 525-532.
2.	［2］Peipins LA, sandler RS. Epidemiology of colorectal adenomas[J]. Epidemiol Rev, 1994; 16(2):272-297.
3.	［3］Neugut AI, Jacobson JS, DeVivo I. Epidemiology of colorectal adenomatous polyps[J]. Cancer Epidemiol Biomarkers Prev,1993; 2 (2): 159-176.
4.	［4］Winawer SJ, Zauber AG, Ho MN, O’Brien MJ, Gottlieb LS, Sternberg SS, Waye JD, Schapiro M, Bond JH, Panish JF, Jerome D. Waye, Melvin Schapiro, John H. Bond, Joel F. Panish, Ackroyd F, Shike M, Kurtz RC, Hornsby-Lewis L, Gerdes H, Stewart ET, The National Polyp Study Workgroup. Prevention of colorectal cancer by colonoscopic polypectomy[J]. N Engl J Med,1993; 329 (27): 1977-1981.
5.	［5］Janne PA, Mayer RJ. Primary care: Chemoprevention of colorectal cancer[J]. N Engl J Med,2000; 342(26):1960-1968.
6.	［6］Collet JP, Sharpe C, Belzile E, Boivin JF, Hanley J, Abenhaim L. Colorectal cancer prevention by non-steroidal anti-inflammatory drugs: effects of dosage and timing[J]. Br J cancer, 1999; 81 (1): 62-68.
7.	［7］Gao X, Sun S, Sun F, Li M, Sun HB,Zhang WD, Song SQ. Nonsteroidal anti-inflammatory drugs and risk of polyposis, colorectal carcinoma[J]. Chinn J Prev Med, 2002; 36(5):332-335.
8.	高雪芹,孙素玲,孙方利,李敏,孙华宾,张维东,宋守芹. 非甾体类抗炎药对肠息肉及结、直肠癌保护作用的病例对照研究[J]. 中华预防医学杂志, 2002; 36(5):332～335.
9.	［8］Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Colditz GA.; Ascherio A; Willett WC. Aspirin Use and the Risk for Colorectal Cancer and adenomas in male health Professionals[J]. Annals of Internal Medicine,1994; 121(4):241-246.
10.	［9］Smalley W, Ray WA, Daugherty J, Griffin MR. Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer: A population-based study[J]. Archives of Internal Medicine, 1999; 159(2):161-166.
11.	［10］Labayle D, Fischer D, Vielh P, Drouhin F, Pariente A, Bories C, Duhamel O, Trousset M, Attali P. Sulindac causes regression of rectal polyps in familial adenomatous polyposis[J]. Gastroenterology, 1991; 101(3):635-639.
12.	［11］Giardiello FM, Hamilton SR, Krush AJ, Piantadosi S, Hylind LM, Celano P, Booker SV, Robinson CR, Offerhaus GJ. Treatment of Colonic and Rectal Adenomas with Sulindac in Familial Adenomatous Polyosis[J]. N Engl J Med, 1993; 328(18):1313-1316.
13.	［12］Baron JA, Cole BF, Sandler RS, Haile RW, Ahnen D, Bresalier R, McKeown-Eyssen G, Summers RW, Rothstein R, Burke CA, Snover DC, Church TR, Allen JI, Beach M, Beck GJ, Bond JH, Byers T, Greenberg ER, Mandel JS, Marcon N, Mott LA, Pearson L, Saibil F, van Stolk RU. A randomized trial of aspirin to prevent colorectal adenomas[J]. N Engl J Med,2003; 348(10):891-899.
14.	［13］Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R, Petrelli N, Pipas JM, Karp DD, Loprinzi CL, Steinbach G, Schilsky R. A randomized trial of aspirin to prevent colorectal adenomas in patients with provious colorectal cancer[J]. N Engl J Med, 2003; 348(10):883-890.
15.	［14］Benamouzig R, Deyra J, Martin A, Girard B, Jullian E, Piednoir B, Couturier D, Coste T, Little J, Chaussade S. Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial[J]. Gastroenterology, 2003; 125(2):328-336.
16.	［15］Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su LK, Levin B.The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis[J]. N Engl J Med, 2000; 342 (26):1946-1952.
17.	［16］Giardiello FM, Yang VW, Hylind LM, Krush AJ, Petersen GM, Trimbath JD, Piantadosi S, Garrett E, Geiman DE, Hubbard W, Offerhaus GJ, Hamilton SR. Primary Chemoprevention of Familial Adenomatous Polyposis with Sulindac[J]. N Engl J Med, 2002; 346(14):1054-1059.
18.	［17］Ladenheim J, Garcia G, Titzer D, Herzenberg H, Lavori P, Edson R, Omary MB. Effect of sulindac on sporadic colonic polyps[J]. Gastroenterology,1995; 108(4):1083-1087.
19.	［18］Chen HP, Han SX, Zeng LM, Xu G, Yang H. Sulindac for treatment of colorectal adenomas[J]. Chin J Dig, 2001; 21(5):340-341.
20.	陈和平,韩盛玺,曾利明,徐刚,杨红. 舒林酸对散发性结肠腺瘤性息肉的疗效[J]. 中华消化杂志, 2001; 21(5):340～341.
21.	［19］Nugent KP, Farmer KC, Spigelman AD, Williams CB, Phillips RK. Randomized controlled trial of effect of sulindac on duodenal and rectal polyposis and cell proliferationa in patients with familial adenomatous polyposis[J]. Br J surg, 1993; 80(12): 1618-1619.
22.	［20］Gann PH, Manson JE, Glynn RJ, Buring JE, Hennekens CH. Low-dose aspirin and incidence of colorectal tumors in a randomized trial[J]. Journal of the National Cancer Institute, 1993; 85(15):1220-1224.
23.	［21］Taketo MM. Cyclooxygenasa-2 inhibitor in tumorigenesis[J]. J Natl Cancer Inst, 1998; 90:1529-1536.
24.	［22］Giovannucci E, Egan KM, Hunter DJ, Stampfer MJ, Colditz GA, Willett WC, Speizer FE. Aspirin and the risk of colorectal Cancer in women[J]. N Engl J Med, 1995; 333 (10):609-614.
25.	［23］Derry S, Loke Yk. Risk of gastrointestinal haemorrhage with long term use of aspirin: Meta-analysis[J]. BMJ, 2000; 321: (7270):1183-1187.
26.	［24］Watson AJ. Are proximal colorectal cancers always associated with distal adenomas[J]? Gut, 2003; 52(3):317-318.
27.	［25］Bond JH. Polyp guideline: diagnosis, treatment, and surveillance for patients with colorectal polyps[J]. The American Journal of Gastroenterology, 2000; 95(11):3053-3063.

1. ［1］Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL. Genetic alterations during colorectal-tumor development[J]. N Engl J Med, 1988; 319 (9): 525-532.
2. ［2］Peipins LA, sandler RS. Epidemiology of colorectal adenomas[J]. Epidemiol Rev, 1994; 16(2):272-297.
3. ［3］Neugut AI, Jacobson JS, DeVivo I. Epidemiology of colorectal adenomatous polyps[J]. Cancer Epidemiol Biomarkers Prev,1993; 2 (2): 159-176.
4. ［4］Winawer SJ, Zauber AG, Ho MN, O’Brien MJ, Gottlieb LS, Sternberg SS, Waye JD, Schapiro M, Bond JH, Panish JF, Jerome D. Waye, Melvin Schapiro, John H. Bond, Joel F. Panish, Ackroyd F, Shike M, Kurtz RC, Hornsby-Lewis L, Gerdes H, Stewart ET, The National Polyp Study Workgroup. Prevention of colorectal cancer by colonoscopic polypectomy[J]. N Engl J Med,1993; 329 (27): 1977-1981.
5. ［5］Janne PA, Mayer RJ. Primary care: Chemoprevention of colorectal cancer[J]. N Engl J Med,2000; 342(26):1960-1968.
6. ［6］Collet JP, Sharpe C, Belzile E, Boivin JF, Hanley J, Abenhaim L. Colorectal cancer prevention by non-steroidal anti-inflammatory drugs: effects of dosage and timing[J]. Br J cancer, 1999; 81 (1): 62-68.
7. ［7］Gao X, Sun S, Sun F, Li M, Sun HB,Zhang WD, Song SQ. Nonsteroidal anti-inflammatory drugs and risk of polyposis, colorectal carcinoma[J]. Chinn J Prev Med, 2002; 36(5):332-335.
8. 高雪芹,孙素玲,孙方利,李敏,孙华宾,张维东,宋守芹. 非甾体类抗炎药对肠息肉及结、直肠癌保护作用的病例对照研究[J]. 中华预防医学杂志, 2002; 36(5):332～335.
9. ［8］Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Colditz GA.; Ascherio A; Willett WC. Aspirin Use and the Risk for Colorectal Cancer and adenomas in male health Professionals[J]. Annals of Internal Medicine,1994; 121(4):241-246.
10. ［9］Smalley W, Ray WA, Daugherty J, Griffin MR. Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer: A population-based study[J]. Archives of Internal Medicine, 1999; 159(2):161-166.
11. ［10］Labayle D, Fischer D, Vielh P, Drouhin F, Pariente A, Bories C, Duhamel O, Trousset M, Attali P. Sulindac causes regression of rectal polyps in familial adenomatous polyposis[J]. Gastroenterology, 1991; 101(3):635-639.
12. ［11］Giardiello FM, Hamilton SR, Krush AJ, Piantadosi S, Hylind LM, Celano P, Booker SV, Robinson CR, Offerhaus GJ. Treatment of Colonic and Rectal Adenomas with Sulindac in Familial Adenomatous Polyosis[J]. N Engl J Med, 1993; 328(18):1313-1316.
13. ［12］Baron JA, Cole BF, Sandler RS, Haile RW, Ahnen D, Bresalier R, McKeown-Eyssen G, Summers RW, Rothstein R, Burke CA, Snover DC, Church TR, Allen JI, Beach M, Beck GJ, Bond JH, Byers T, Greenberg ER, Mandel JS, Marcon N, Mott LA, Pearson L, Saibil F, van Stolk RU. A randomized trial of aspirin to prevent colorectal adenomas[J]. N Engl J Med,2003; 348(10):891-899.
14. ［13］Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R, Petrelli N, Pipas JM, Karp DD, Loprinzi CL, Steinbach G, Schilsky R. A randomized trial of aspirin to prevent colorectal adenomas in patients with provious colorectal cancer[J]. N Engl J Med, 2003; 348(10):883-890.
15. ［14］Benamouzig R, Deyra J, Martin A, Girard B, Jullian E, Piednoir B, Couturier D, Coste T, Little J, Chaussade S. Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial[J]. Gastroenterology, 2003; 125(2):328-336.
16. ［15］Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su LK, Levin B.The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis[J]. N Engl J Med, 2000; 342 (26):1946-1952.
17. ［16］Giardiello FM, Yang VW, Hylind LM, Krush AJ, Petersen GM, Trimbath JD, Piantadosi S, Garrett E, Geiman DE, Hubbard W, Offerhaus GJ, Hamilton SR. Primary Chemoprevention of Familial Adenomatous Polyposis with Sulindac[J]. N Engl J Med, 2002; 346(14):1054-1059.
18. ［17］Ladenheim J, Garcia G, Titzer D, Herzenberg H, Lavori P, Edson R, Omary MB. Effect of sulindac on sporadic colonic polyps[J]. Gastroenterology,1995; 108(4):1083-1087.
19. ［18］Chen HP, Han SX, Zeng LM, Xu G, Yang H. Sulindac for treatment of colorectal adenomas[J]. Chin J Dig, 2001; 21(5):340-341.
20. 陈和平,韩盛玺,曾利明,徐刚,杨红. 舒林酸对散发性结肠腺瘤性息肉的疗效[J]. 中华消化杂志, 2001; 21(5):340～341.
21. ［19］Nugent KP, Farmer KC, Spigelman AD, Williams CB, Phillips RK. Randomized controlled trial of effect of sulindac on duodenal and rectal polyposis and cell proliferationa in patients with familial adenomatous polyposis[J]. Br J surg, 1993; 80(12): 1618-1619.
22. ［20］Gann PH, Manson JE, Glynn RJ, Buring JE, Hennekens CH. Low-dose aspirin and incidence of colorectal tumors in a randomized trial[J]. Journal of the National Cancer Institute, 1993; 85(15):1220-1224.
23. ［21］Taketo MM. Cyclooxygenasa-2 inhibitor in tumorigenesis[J]. J Natl Cancer Inst, 1998; 90:1529-1536.
24. ［22］Giovannucci E, Egan KM, Hunter DJ, Stampfer MJ, Colditz GA, Willett WC, Speizer FE. Aspirin and the risk of colorectal Cancer in women[J]. N Engl J Med, 1995; 333 (10):609-614.
25. ［23］Derry S, Loke Yk. Risk of gastrointestinal haemorrhage with long term use of aspirin: Meta-analysis[J]. BMJ, 2000; 321: (7270):1183-1187.
26. ［24］Watson AJ. Are proximal colorectal cancers always associated with distal adenomas[J]? Gut, 2003; 52(3):317-318.
27. ［25］Bond JH. Polyp guideline: diagnosis, treatment, and surveillance for patients with colorectal polyps[J]. The American Journal of Gastroenterology, 2000; 95(11):3053-3063.

Chinese Journal of Evidence-Based Medicine

Nonsteroidal Anti-inflammatory Drugs for Prevention of Colorectal Neoplasms: A Systematic Review

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