Current Treatment Options in Oncology

, Volume 5, Issue 5, pp 417–426 | Cite as

Strategies for prevention of colorectal cancer: Pharmaceutical and nutritional interventions

  • Christopher D. Lao
  • Dean E. Brenner
Article

Opinion statement

Interventions designed to delay or prevent the development of invasive colorectal adenocarcinoma might result in a profound impact on the incidence of and mortality from colorectal cancer. Current developmental efforts focus in two major directions: identification and testing of combination-targeted signal transduction pathway modu-lators and development of nutriceuticals. Both approaches recognize the heterogene-ity of the carcinogenesis process. Combinations of agents (eg, aspirin or sulindac with DFMO, calcium with fiber), which have complementary or synergistic mechanisms or agents with broad spectrum anti-carcinogenic effects can potentially improve upon the effects of single agents and account for redundant signal transduction pathways involved in uncontrolled growth of clonal cells. Preliminary data in rodent systems suggest nutriceuticals or standardized foodstuffs, which contain multiple components, many of which are not identified have synergistic anticarcinogenesis effects. Diet modulation or supplementation with known standardized foodstuffs may be ideal in individuals at risk for colorectal cancer. Current clinical models for colorectal cancer prevention focus upon a pathologic-surrogate endpoint (reducing the recurrence or emergence of adenomas). This surrogate, generally accepted at a regulatory level, might not represent the true malignant progression from normal colonic mucosa to the malignant phenotype. Could the intervention simply prevent the emergence of ade-nomas that would not have progressed to invasive neoplasia in any event? Despite this major weakness, the adenoma remains the regulatory endpoint for efficacy because the cancer event remains rare, even among individuals selected as high-risk epidemiology but without known, highly pressured genetic-based stress. Over the next decade, the emergence of molecular and proteomic profiling tools have the potential of selecting adenomas that will progress to adenocarcinomas and will allow for investigation to be focused on individuals at increased risk.

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References and Recommended Reading

  1. 1.
    Colbert LH, Lanza E, Ballard-Barbash R, et al.: Adenom-atous polyp recurrence and physical activity in the Polyp Prevention Trial (United States). Cancer Causes Control 2002, 13:445–453.PubMedCrossRefGoogle Scholar
  2. 2.
    Colbert LH, Hartman TJ, Malila N, et al.: Physical activ-ity in relation to cancer of the colon and rectum in a cohort of male smokers. Cancer Epidemiol Biomarkers Prev 2001, 10:265–268.PubMedGoogle Scholar
  3. 3.
    Slattery ML: Physical activity and colorectal cancer. Sports Med 2004, 34:239–252.PubMedCrossRefGoogle Scholar
  4. 4.
    Michels KB, Edward G, Joshipura KJ, et al.: Prospective study of fruit and vegetable consumption and inci-dence of colon and rectal cancers. J Natl Cancer Inst 2000, 92:1740–1752.PubMedCrossRefGoogle Scholar
  5. 5.
    Jansen MC, Bueno-de-Mesquita HB, Buzina R, et al.: Dietary fiber and plant foods in relation to colorectal cancer mortality: the Seven Countries Study. Int J Can-cer 1999, 81:174–179.Google Scholar
  6. 6.
    McCullough ML, Robertson AS, Chao A, et al.: A prospec-tive study of whole grains, fruits, vegetables and colon cancer risk. Cancer Causes Control 2003, 14:959–970.PubMedCrossRefGoogle Scholar
  7. 7.
    Miller AB, Altenburg HP, Bueno-de-Mesquita B, et al.: Fruits and vegetables and lung cancer: findings from the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 2004, 108:269–276.PubMedCrossRefGoogle Scholar
  8. 8.
    Slattery ML, Curtin KP, Edwards SL, et al.: Plant foods, fiber, and rectal cancer. Am J Clin Nutr 2004, 79:274–281.PubMedGoogle Scholar
  9. 9.
    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.PubMedCrossRefGoogle Scholar
  10. 10.
    Cruz-Correa M, Hylind LM, Romans KE, et al.: Long-term treatment with sulindac in familial adenoma-tous polyposis: a prospective cohort study. Gastroenter-ology 2002, 122:641–645.CrossRefGoogle Scholar
  11. 11.
    Giardiello FM, Yang VW, Hylind LM, et al.: Primary chemoprevention of familial adenomatous polyposis with sulindac. N Engl J Med 2002, 346:1054–1059.PubMedCrossRefGoogle Scholar
  12. 12.
    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. This randomized clinical prevention trial addresses the effect of different doses of a putative chemopreventive agent (aspirin) and the combination of putative agents (aspirin and folate). Although a modest effect in preventing recurrent adenomas was seen, this study addresses important issues in the field of preven-tion (ie, optimal dose over maximum tolerated dose and the effect and tolerance of combination agents in humans).PubMedCrossRefGoogle Scholar
  13. 13.
    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. This randomized clinical trial provides additional support for aspirin as an effective agent at reducing recurrent polyps, which presumably will prevent a certain number of invasive cancers.PubMedCrossRefGoogle Scholar
  14. 14.
    Benamouzig R, Deyra J, Martin A, et al.: Daily soluble aspirin and prevention of colorectal adenoma recur-rence: one-year results of the APACC trial. Gastroenter-ology 2003, 125:328–336.CrossRefGoogle Scholar
  15. 15.
    Chan AT, Giovannucci EL, Schernhammer ES, et al.: A prospective study of aspirin use and the risk for col-orectal adenoma. Ann Intern Med 2004, 140:157–166.PubMedGoogle Scholar
  16. 16.
    Schernhammer ES, Kang JH, Chan AT, et al.: A prospec-tive study of aspirin use and the risk of pancreatic cancer in women. J Natl Cancer Inst 2004, 96:22–28.PubMedCrossRefGoogle Scholar
  17. 17.
    Suleiman S, Rex DK, Sonnenberg A: Chemoprevention of colorectal cancer by aspirin: a cost-effectiveness analysis. Gastroenterology 2002, 122:78–84.PubMedCrossRefGoogle Scholar
  18. 18.
    Steinbach G, Lynch PM, Phillips RK, et al.: The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000, 342:1946–1952. This randomized clinical trial led to the only currently FDA-approved agent, celecoxib, for colorectal cancer chemoprevention.PubMedCrossRefGoogle Scholar
  19. 19.
    Higuchi T, Iwama T, Yoshinaga K, et al.: A randomized, double-blind, placebo-controlled trial of the effects of rofecoxib, a selective cyclooxygenase-2 inhibitor, on rectal polyps in familial adenomatous polyposis patients. Clin Cancer Res 2003, 9:4756–4760.PubMedGoogle Scholar
  20. 20.
    Terry P, Giovannucci E, Michels KB, et al.: Fruit, vegeta-bles, dietary fiber, and risk of colorectal cancer. J Natl Cancer Inst 2001, 93:525–533.PubMedCrossRefGoogle Scholar
  21. 21.
    Pietinen P, Malila N, Virtanen M, et al.: Diet and risk of colorectal cancer in a cohort of Finnish men. Cancer Causes Control 1999, 10:387–396.PubMedCrossRefGoogle Scholar
  22. 22.
    Peters U, Sinha R, Chatterjee N, et al.: Dietary fibre and colorectal adenoma in a colorectal cancer early detec-tion programme. Lancet 2003, 361:1491–1495.PubMedCrossRefGoogle Scholar
  23. 23.
    Bingham SA, Day NE, Luben R, et al.: Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): an observational study. Lancet 2003, 361:1496–1501.PubMedCrossRefGoogle Scholar
  24. 24.
    Alberts DS, Martinez ME, Roe DJ, et al.: Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Preven-tion Physicians’ Network. N Engl J Med 2000, 342:1156–1162.PubMedCrossRefGoogle Scholar
  25. 25.
    Schatzkin A, Lanza E, Corle D, et al.: Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. N Engl J Med 2000, 342:1149–1155.PubMedCrossRefGoogle Scholar
  26. 26.
    Baron JA, Beach M, Mandel JS, et al.: Calcium supple-ments for the prevention of colorectal adenomas. Cal-cium Polyp Prevention Study Group. N Engl J Med 1999, 340:101–107. This study provides evidence from a randomized placebo-con-trolled clinical trial that calcium has chemopreventive activity.PubMedCrossRefGoogle Scholar
  27. 27.
    Grau MV, Baron JA, Sandler RS, et al.: Vitamin D, cal-cium supplementation, and colorectal adenomas: results of a randomized trial. J Natl Cancer Inst 2003, 95:1765–1771.PubMedGoogle Scholar
  28. 28.
    Baron J, Sandler R, Haile R, et al.: Folate intake, alcohol consumption, cigarette smoking, and risk of colorec-tal adenomas. J Natl Cancer Inst 1998, 90:57–62.PubMedCrossRefGoogle Scholar
  29. 29.
    Bird C, Swendseid M, Witte J, et al.: Red cell and plasma folate, folate consumption, and the risk of colorectal adenomatous polyps. Cancer Epidemiol Biomarkers Prev 1995, 4:709–714.PubMedGoogle Scholar
  30. 30.
    Mason J: Folate and colon cancer: a fascinating puzzle we have yet to complete. Clin Nutr 1998, 17:41–43.PubMedCrossRefGoogle Scholar
  31. 31.
    Giovannucci E, Stampfer MJ, Colditz GA, et al.: Multivita-min use, folate, and colon cancer in women in the Nurses’ Health Study. Ann Intern Med 1998, 129:517–524.PubMedGoogle Scholar
  32. 32.
    Su LJ, Arab L: Nutritional status of folate and colon cancer risk: evidence from NHANES I epidemiologic follow-up study. Ann Epidemiol 2001, 11(1):65–72.PubMedCrossRefGoogle Scholar
  33. 33.
    Wu K, Willett WC, Chan JM, et al.: A prospective study on supplemental vitamin e intake and risk of colon cancer in women and men. Cancer Epidemiol Biomarkers Prev 2002, 11:1298–1304.PubMedGoogle Scholar
  34. 34.
    Greenberg ER, Baron JA, Tosteson TD, et al.: A clinical trial of antioxidant vitamins to prevent colorectal ade-noma. Polyp Prevention Study Group. N Engl J Med 1994, 331(3):141–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Albanes D, Malila N, Taylor PR, et al.: Effects of supple-mental alpha-tocopherol and beta-carotene on col-orectal cancer: results from a controlled trial (Finland). Cancer Causes Control 2000, 11:197–205.PubMedCrossRefGoogle Scholar
  36. 36.
    Klein EA, Thompson IM, Lippman SM, et al.: SELECT: the Selenium and Vitamin E Cancer Prevention Trial: rationale and design. Prostate Cancer Prostatic Dis 2000, 3:145–151.PubMedCrossRefGoogle Scholar
  37. 37.
    Cook NR, Le IM, Manson JE, et al.: Effects of beta-caro-tene supplementation on cancer incidence by baseline characteristics in the Physicians’ Health Study (United States). Cancer Causes Control 2000, 11:617–626.PubMedCrossRefGoogle Scholar
  38. 38.
    Baron JA, Cole BF, Mott L, et al.: Neoplastic and antine-oplastic effects of beta-carotene on colorectal ade-noma recurrence: results of a randomized trial. J Natl Cancer Inst 2003, 95:717–722.PubMedCrossRefGoogle Scholar
  39. 39.
    Malila N, Virtamo J, Virtanen M, et al.: Dietary and serum alpha-tocopherol, beta-carotene and retinol, and risk for colorectal cancer in male smokers. Eur J Clin Nutr 2002, 56:615–621.PubMedCrossRefGoogle Scholar
  40. 40.
    Duffield-Lillico AJ, Reid ME, Turnbull BW, et al.: Base-line characteristics and the effect of selenium supple-mentation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Pre-vention of Cancer Trial. Cancer Epidemiol Biomarkers Prev 2002, 11:630–639.PubMedGoogle Scholar
  41. 41.
    Jacobs EJ, Connell CJ, Patel AV, et al.: Vitamin C and vitamin E supplement use and colorectal cancer mor-tality in a large American Cancer Society cohort. Can-cer Epidemiol Biomarkers Prev 2001, 10:17–23.Google Scholar
  42. 42.
    Leu T, Maa M: The molecular mechanisms for the anti-tumorigenic effect of curcumin. Curr Med Chem Anti-Canc Agents 2002, 2:357–370.CrossRefGoogle Scholar
  43. 43.
    Rao CV, Rivenson A, Simi B, et al.: Chemoprevention of colon cancer by dietary curcumin. Ann N Y Acad Sci 1995, 768:201–204.PubMedCrossRefGoogle Scholar
  44. 44.
    Ramsewak RS, DeWitt DL, Nair MG: Cytotoxicity, antioxi-dant and anti-inflammatory activities of curcumins I-III from Curcuma longa. Phytomedicine 2000, 7:303–308.PubMedGoogle Scholar
  45. 45.
    Cheng AL, Hsu CH, Lin JK, et al.: Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 2001, 21:2895–2900.PubMedGoogle Scholar
  46. 46.
    Meyskens FL Jr, Gerner EW: Development of difluo-romethylornithine (DFMO) as a chemoprevention agent. Clin Cancer Res 1999, 5:945–951.PubMedGoogle Scholar
  47. 47.
    Kresty L, Morse M, Morgan C, et al.: Chemoprevention of esophageal tumorigenesis in dietary administra-tion of lyophilized black raspberries. Cancer Res 2001, 61:6112–6119. Evidence of preventive efficacy of a standardized food from a preclinical in vivo rodent model of esophageal carcinogenesis.PubMedGoogle Scholar
  48. 48.
    Harris G, Gupta A, Nines R, et al.: The effects of lyo-philized black raspberries on azoxymethane-induced colon cancer and 8-hydroxy-2’-deoxyguanosine levels in the Fishcer 344 rat. Nutr Cancer 2001, 40:125–133.PubMedCrossRefGoogle Scholar
  49. 49.
    Li H, Kramer P, Lubet R, et al.: Effects of calcium on azoxymethane-induced aberrant crypt foci and cell proliferation in the colon of rats. Cancer Lett 1998, 124:39–46.PubMedCrossRefGoogle Scholar
  50. 50.
    Deschner EE, Cohen BI, Raicht RF: The kinetics of the protective effect of beta-sitosterol against MNU-induced colonic neoplasia. J Cancer Res Clin Oncol 1982, 103:49–54.PubMedCrossRefGoogle Scholar
  51. 51.
    Rao C, Tokumo K, Rigotty J, et al.: Chemoprevention of colon carcinogenesis by dietary administration of piroxicam, a-difluoromethylornithine, 16-a-fluoro-5- androsten-17-one, and ellagic acid individually and in combination. Cancer Res 1991:4528-4553.Google Scholar
  52. 52.
    Kawabata K, Yamamoto K, Rigotty J, et al.: Chemopre-vention of colon carcinogenesis by dietary adminis-tration of piroxicam, alpha-difluoromethylornithine, 16-alpha-fluoro-5-adrosten-17-one and ellagic acid individually and in combination. Cancer Res 1991, 51:4528–4534.Google Scholar
  53. 53.
    Coffey R, Hawkey C, Damstrup L, et al.: Epidermal growth factor receptor activation induces nuclear tar-geting of cyclooxygenase-2, basolateral release of prostaglandins, and mitogenesis in polarizing colon cancer cells. Proc Natl Acad Sci USA 1997, 94:657–662.PubMedCrossRefGoogle Scholar
  54. 54.
    Torrance CJ, Jackson PE, Montgomery E, et al.: Combi-natorial chemoprevention of intestinal neoplasia. Nat Med 2000, 6:1024–1028. This article demonstrates mechanistic translation of synergis-tic efficacy of combined preventive pharmaceutical interven-tions in a preclinical in vivo model.PubMedCrossRefGoogle Scholar
  55. 55.
    Agarwal B, Rao CV, Bhendwal S, et al.: Lovastatin aug-ments sulindac-induced apoptosis in colon cancer cells and potentiates chemopreventive effects of sulin-dac. Gastroenterology 1999, 117:838–847.PubMedCrossRefGoogle Scholar
  56. 56.
    Swamy MV, Cooma I, Reddy BS, et al.: Lamin B, caspase-3 activity, and apoptosis induction by a combination of HMG-CoA reductase inhibitor and COX-2 inhibitors: a novel approach in developing effective chemopreven-tive regimens. Int J Oncol 2002, 20:753–759. Preclinical model demonstrating statin-NSAID preventive efficacy.PubMedGoogle Scholar

Copyright information

© Current Science Inc 2004

Authors and Affiliations

  • Christopher D. Lao
  • Dean E. Brenner
    • 1
  1. 1.University of MichiganAnn ArborUSA

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