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Coxibs: Pharmacology, Toxicity and Efficacy in Cancer Clinical Trials

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Prospects for Chemoprevention of Colorectal Neoplasia

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 191))

Abstract

This chapter briefly summarizes the current knowledge about the role of nonsteroidal anti-inflammatory drugs (NSAIDs), specially focusing on those selective for cyclooxygenase (COX)-2 (coxibs), on colorectal cancer (CRC) onset, and progression. Both epidemiological and experimental studies have reported that these drugs reduce the risk of developing colonic tumors. However, the promising use of coxibs in chemoprevention was halted abruptly due to the detection on enhanced cardiovascular (CV) risks. Thus, we discuss the clinical data and plausible mechanisms of CV hazards associated with traditional NSAIDs and coxibs. The extent of inhibition of COX-2-dependent prostacyclin, an important vasoprotective and anti-thrombotic pathway, in the absence of a complete suppression of COX-1-dependent platelet function, at common doses of NSAIDs, might play a role in CV toxicity. Coxibs might still be reserved for younger patients with familial adenomatous polyposis (FAP). However, it should be taken into consideration that recent findings of enhanced thromboxane (TX)A2 biosynthesis in colon tumorigenesis, detected in humans. In this context, the use of low-dose aspirin (which mainly acts by inhibiting platelet COX-1-dependent TXA2) may have a place for chemoprevention of CRCs (see also Chap. 3). The possible use of coxibs to prevent CRC will depend mainly on research progresses in biomarkers able to identify the patients uniquely susceptible to developing thrombotic events by inhibition of COX-2.

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Abbreviations

AMI:

Acute myocardial infarction

ASA:

Aspirin

CV:

Cardiovascular

CNS:

Central nervous system

CRC:

Colorectal cancer

COX:

Cyclooxygenase

EMA:

European medicine agency

EU:

European union

FAP:

Familial adenomatous polyposis

FDA:

Food and drug administration

GI:

Gastrointestinal

PGI2 :

Prostacyclin

PG:

Prostaglandin

RCT:

Randomized clinical trial

RR:

Relative risk

RA:

Rheumatoid arthritis

TXA2 :

Thromboxane

tNSAID:

Traditional nonsteroidal anti-inflammatory drug

US:

United States

References

  • Andersohn F, Suissa S, Garbe E (2006) Use of first- and second-generation cyclooxygenase-2-selective nonsteroidal antiinflammatory drugs and risk of acute myocardial infarction. Circulation 113:1950–1957

    CAS  PubMed  Google Scholar 

  • Antman EM, Bennett JS, Daugherty A et al (2007) Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American heart association. Circulation 115:1634–1642

    PubMed  Google Scholar 

  • Anzellotti P, Capone ML, Jeyam A et al (2011) Low-dose naproxen interferes with the antiplatelet effects of aspirin in healthy subjects: recommendations to minimize the functional consequences. Arthritis Rheum 63:850–859

    CAS  PubMed  Google Scholar 

  • Arber N (2008) Cyclooxygenase-2 inhibitors in colorectal cancer prevention: point. Cancer Epidemiol Biomarkers Prev 17:1852–1857

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Arehart E, Stitham E, Asselbergs FW et al (2008) Acceleration of cardiovascular disease by a dysfunctional prost acyclin receptor mutation: potential implications for cyclooxygenase-2 inhibition. Circ Res 102:986–993

    CAS  PubMed  Google Scholar 

  • Baek SJ, Kim KS, Nixon JB et al (2001) Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities. Mol Pharmacol 59:901–908

    CAS  PubMed  Google Scholar 

  • Baigent C, Blackwell L, Collins R et al (2009) Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 373:1849–1860

    PubMed  Google Scholar 

  • Bhatt DL, Scheiman J, Abraham NS et al (2008) ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. In: A report of the American college of cardiology foundation task force on clinical expert consensus documents, vol 52, pp 1502–1517

    Google Scholar 

  • Bak S, Andersen M, Tsiropoulos I et al (2003) Risk of stroke associated with nonsteroidal anti-inflammatory drugs: a nested case-control study. Stroke 34:379–386

    CAS  PubMed  Google Scholar 

  • Baron JA, Sandler RS, Bresalier RS et al (2006) A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterology 131:1674–1682

    CAS  PubMed  Google Scholar 

  • Baron JA, Sandler RS, Bresalier RS et al (2008) Cardiovascular events associated with rofecoxib: final analysis of the Approve trial. Lancet 372:1756–1764

    CAS  PubMed  Google Scholar 

  • Bautista D, Obrador A, Moreno V et al (1997) Ki-ras mutation modifies the protective effect of dietary monounsaturated fat and calcium on sporadic colorectal cancer. Cancer Epidemiol Biomarkers Prev 6:57–61

    CAS  PubMed  Google Scholar 

  • Becker MC, Wang TH, Wisniewski L et al (2009) Rationale, design, and governance of prospective randomized evaluation of celecoxib integrated safety versus ibuprofen or naproxen (PRECISION), a cardiovascular end point trial of nonsteroidal antiinflammatory agents in patients with arthritis. Am Heart J 157:606–612

    CAS  PubMed  Google Scholar 

  • Bennett A, Del Tacca M (1975) Proceedings: prostaglandins in human colonic carcinoma. Gut 16:409

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Bisoendial RJ, Kastelein JJP, Peters SLM et al (2007) Effects of CRP infusion on endothelial function and coagulation in normocholesterolemic and hypercholesterolemic subjects. J Lipid Res 48:952–960

    CAS  PubMed  Google Scholar 

  • Bombardier C, Laine L, Reicin A et al (2000) Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR study group. N Engl J Med 343:1520–1528

    CAS  PubMed  Google Scholar 

  • Boursi B, Arber N (2007) Current and future clinical strategies in colon cancer prevention and the emerging role of chemoprevention. Curr Pharm Des 13:2274–2282

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Brun J, Jones R (2001) Nonsteroidal anti-inflammatory drug-associated dyspepsia: the scale of the problem. Am J Med 110:12S–13S

    CAS  PubMed  Google Scholar 

  • Buchanan FG, DuBois RN (2006) Connecting COX-2 and wnt in cancer. Cancer Cell 9:6–8

    CAS  PubMed  Google Scholar 

  • Bueno H, Bardají A, Patrignani P et al (2010) Spanish case-control study to assess NSAID-associated ACS risk investigators. Use of non-steroidal antiinflammatory drugs and type-specific risk of acute coronary syndrome. Am J Cardiol 105:1102–1106

    CAS  PubMed  Google Scholar 

  • Burke A, Smyth EM, FitzGerald GA (2006) Analgesic-antipyretic agents; pharmacotherapy of gout. In: Brunton LL, Lazo JS, Parker KL (eds) Goodman and Gilman’s the pharmacological basis of therapeutics, 11th edn. McGraw-Hill, New York

    Google Scholar 

  • Campos FG, Logullo Waitzberg AG et al (2005) Diet and colorectal cancer: current evidence for etiology and prevention. Nutr Hosp 20:18–25

    CAS  PubMed  Google Scholar 

  • Capone ML, Sciulli MG, Tacconelli S et al (2005) Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects. J Am Coll Cardiol 45:1295–1301

    CAS  PubMed  Google Scholar 

  • Capone ML, Tacconelli S, Di Francesco L et al (2007) Pharmacodynamic of cyclooxygenase inhibitors in humans. Prostaglandins Other Lipid Mediat 82:85–94

    CAS  PubMed  Google Scholar 

  • Capone ML, Tacconelli S, Sciulli MG et al (2004) Clinical pharmacology of platelet, monocyte, and vascular cyclooxygenase inhibition by naproxen and low-dose aspirin in healthy subjects. Circulation 109:1468–1471

    CAS  PubMed  Google Scholar 

  • Catella-Lawson F, Reilly MP, Kapoor SC et al (2001) Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med 345:1809–1817

    CAS  PubMed  Google Scholar 

  • Cha YI, DuBois RN (2007) NSAIDs and cancer prevention: targets downstream of COX-2. Annu Rev Med 58:239–252

    CAS  PubMed  Google Scholar 

  • Chan AT, Sima SS, Zauber AG (2011) C-reactive protein and risk of colorectal adenoma according to celecoxib treatment. Cancer Prev Res 4:1172–1180

    CAS  Google Scholar 

  • Chang CH, Shau WY, Kuo CW et al (2010) Increased risk of stroke associated with nonsteroidal anti-inflammatory drugs: a nationwide case-crossover study. Stroke 41:1884–1890

    CAS  PubMed  Google Scholar 

  • Chan FK, Chung SC, Suen BY et al (2001) Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med 344:967–973

    CAS  PubMed  Google Scholar 

  • Chan TA (2002) Nonsteroidal anti-inflammatory drugs, apoptosis, and colon-cancer chemoprevention. Lancet Oncol 3:166–174

    CAS  PubMed  Google Scholar 

  • Cheng I, Caberto CP, Lum-Jones A et al (2011) Type two diabetes risk variants and colorectal cancer risk: the multiethnic cohort and PAGE studies. Gut (May 20 [Epub ahead of print])

    Google Scholar 

  • Choi NK, Park BJ, Jeong SW et al (2008) Nonaspirin nonsteroidal anti-inflammatory drugs and hemorrhagic stroke risk: the acute brain bleeding analysis study. Stroke 39:845–849

    CAS  PubMed  Google Scholar 

  • Choti MA, Sitzmann JV, Tiburi MF et al (2002) Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg 235:759–766

    PubMed  Google Scholar 

  • Curtis JP, Wang Y, Portnay EL et al (2003) Aspirin, ibuprofen, and mortality after myocardial infarction: retrospective cohort study. BMJ 327:1322–1323

    PubMed  Google Scholar 

  • Dannenberg AJ, Altorki NK, Boyle JO et al (2001) Cyclo-oxygenase 2: a pharmacological target for the prevention of cancer. Lancet Oncol 2:544–551

    CAS  PubMed  Google Scholar 

  • Danenberg H, Szalai A, Swaminathan R et al (2003) Increased thrombosis following injury in human C-reactive protein transgenic mice. Circulation 108:512–515

    CAS  PubMed  Google Scholar 

  • Di Francesco L, Totani L, Dovizio M et al (2009) Induction of prostacyclin by steady laminar shear stress suppresses tumor necrosis factor-alpha biosynthesis via heme oxygenase-1 in human endothelial cells. Circ Res 104:506–513

    PubMed  Google Scholar 

  • DuBois RN, Radhika A, Reddy BS et al (1996) Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors. Gastroenterology 110:1259–1262

    CAS  PubMed  Google Scholar 

  • Eberhart CE, Coffey RJ, Radhika A et al (1994) Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 107:1183–1188

    CAS  PubMed  Google Scholar 

  • Farkouh ME, Kirshner H, Harrington RA et al (2004) Comparison of lumiracoxib with naproxen and ibuprofen in the therapeutic arthritis research and gastrointestinal event trial (TARGET), cardiovascular outcomes: randomised controlled trial. Lancet 364:675–684

    CAS  PubMed  Google Scholar 

  • Ferrandez A, Prescott S, Burt RW (2003) COX-2 and colorectal cancer. Curr Pharm Des 9:2229–2251

    CAS  PubMed  Google Scholar 

  • Fischer LM, Schlienger RG, Matter CM et al (2004) Discontinuation of non-steroidal anti-inflammatory drug therapy and the risk of acute myocardial infarction. Arch Intern Med 164:2472–2476

    CAS  PubMed  Google Scholar 

  • FitzGerald GA, Patrono C (2001) The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 345:433–442

    CAS  PubMed  Google Scholar 

  • Fuchs CS, Giovannucci EL, Colditz GA et al (1999) Dietary fiber and the risk of colorectal cancer and adenoma in women. N Engl J Med 340:169–176

    CAS  PubMed  Google Scholar 

  • Garcia Rodriguez LA, Ruigomez A, Wallander MA et al (2000) Detection of colorectal tumor and inflammatory bowel disease during follow-up of patients with initial diagnosis of irritable bowel syndrome. Scand J Gastroenterol 35:306–311

    CAS  PubMed  Google Scholar 

  • García Rodríguez LA, Varas-Lorenzo C, Maguire A et al (2004) A non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population. Circulation 109:3000–3006

    PubMed  Google Scholar 

  • García-Rodríguez LA, Tacconelli S, Patrignani P (2008) Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population. JACC 52:1628–1636

    PubMed  Google Scholar 

  • Giouleme O, Diamantidis MD, Marios Katsaros G (2011) Is diabetes a causal agent for colorectal cancer? Pathophysiological and molecular mechanisms. World J Gastroenterol 17:444–448

    CAS  PubMed  Google Scholar 

  • Giovannucci E (2002) Modifiable risk factors for colon cancer. Gastroenterol Clin North Am 31:925–943

    PubMed  Google Scholar 

  • Gislason GH, Jacobsen S, Rasmussen JN et al (2006) Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction. Circulation 113:2906–2913

    CAS  PubMed  Google Scholar 

  • Goel A, Chang DK, Ricciardiello L et al (2003) A novel mechanism for aspirin-mediated growth inhibition of human colon cancer cells. Clin Cancer Res 9:383–390

    CAS  PubMed  Google Scholar 

  • Grad E, Golomb M, Koroukhov N et al (2009) Aspirin reduces the prothrombotic activity of C-reactive protein. J Thromb Haemost 7:1393–1400

    CAS  PubMed  Google Scholar 

  • Graham DJ, Campen D, Hui R et al (2005) Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase two selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet 365:4996–5002

    Google Scholar 

  • Greenberg ER, Baron JA, Tosteson TD et al (1994) A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp prevention study group. N Engl J Med 331:141–147

    CAS  PubMed  Google Scholar 

  • Grosser T, Fries S, FitzGerald GA (2006) Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest 116:4–15

    CAS  PubMed  Google Scholar 

  • Haag MD, Bos MJ, Hofman A et al (2008) Cyclooxygenase selectivity of nonsteroidal anti-inflammatory drugs and risk of stroke. Arch Intern Med 168:1219–1224

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Hao X, Bishop AE, Wallace M et al (1999) Early expression of cyclo-oxygenase-2 during sporadic colorectal carcinogenesis. J Pathol 187:295–301

    CAS  PubMed  Google Scholar 

  • Headrick JR, Miller DL, Nagorney DM et al (2001) Surgical treatment of hepatic and pulmonary metastases from colon cancer. Ann Thorac Surg 71:975–980

    CAS  PubMed  Google Scholar 

  • Helin-Salmivaara A, Virtanen A, Vesalainen R et al (2006) NSAID use and the risk of hospitalization for first myocardial infarction in the general population: a nationwide case-control study from Finland. Eur Heart J 27:1657–1663

    PubMed  Google Scholar 

  • Hennekens CH, Buring JE, Manson JE et al (1996) Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 334:1145–1159

    CAS  PubMed  Google Scholar 

  • Hernández-Díaz S, García Rodríguez LA (2000) Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation. An overview of epidemiologic studies published in the 1990s. Arch Intern Med 160:2093–2099

    PubMed  Google Scholar 

  • Hernandez-Diaz S, Varas-Lorenzo C, Garcia Rodriguez LA (2006) Non-steroidal antiinflammatory drugs and the risk of acute myocardial infarction. Basic Clin Pharmacol Toxicol 98:266–274

    CAS  PubMed  Google Scholar 

  • Hippisley-Cox J, Coupland C (2005) Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ 330:1366–1372

    CAS  PubMed  Google Scholar 

  • Hong WK, Lippman SM, Itri LM et al (1990) Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323:795–801

    CAS  PubMed  Google Scholar 

  • Hudson M, Baron M, Rahme E et al (2005) Ibuprofen may abrogate the benefits of aspirin when used for secondary prevention of myocardial infarction. J Rheumatol 32:1589–1593

    CAS  PubMed  Google Scholar 

  • Husain SS, Szabo IL, Tamawski AS (2002) NSAID inhibition of GI cancer growth: clinical implications and molecular mechanisms of action. Am J Gastroenterol 97:542–553

    CAS  PubMed  Google Scholar 

  • Ilkhanoff L, Lewis JD, Hennessy S et al (2005) Potential limitations of electronic database studies of prescription non-aspirin non-steroidal anti-inflammatory drugs (NANSAIDs) and risk of myocardial infarction (MI). Pharmacoepidemiol Drug Saf 14:513–522

    PubMed  Google Scholar 

  • Jaffe BM (1974) Prostaglandins and cancer: an update. Prostaglandins 6:453–461

    CAS  PubMed  Google Scholar 

  • Jana NR (2008) NSAIDs and apoptosis. Cell Mol Life Sci 65:1295–1301

    CAS  PubMed  Google Scholar 

  • Janne PA, Mayer RJ (2000) Chemoprevention of colorectal cancer. N Engl J Med 342:1960–1968

    CAS  PubMed  Google Scholar 

  • Jiang Y, Ben Q, Shen H et al (2011) Diabetes mellitus and incidence and mortality of colorectal cancer: a systematic review and meta-analysis of cohort studies. Eur J Epidemiol [Epub ahead of print]

    Google Scholar 

  • Johnsen SP, Pedersen L, Friis S et al (2003) Nonaspirin nonsteroidal anti-inflammatory drugs and risk of hospitalization for intracerebral hemorrhage: a population-based case-control study. Stroke 34:387–391

    CAS  PubMed  Google Scholar 

  • Johnsen SP, Larsson H, Tarone RE et al (2005) Risk of hospitalization for myocardial infarction among users of rofecoxib, celecoxib, and other NSAIDs. Arch Intern Med 165:978–984

    CAS  PubMed  Google Scholar 

  • Kargman SL, O’Neill GP, Vickers PJ et al (1995) Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res 55:2556–2559

    CAS  PubMed  Google Scholar 

  • Kearney PM, Baigent C, Godwin J et al (2006) Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ 332:1302–1308

    CAS  PubMed  Google Scholar 

  • Kimmel SE, Berlin JA, Reilly M et al (2004) The effects of nonselective non-aspirin non-steroidal anti-inflammatory medications on the risk of nonfatal myocardial infarction and their interaction with aspirin. J Am Coll Cardiol 43:985–990

    CAS  PubMed  Google Scholar 

  • Kimmel SE, Berlin JA, Reilly M et al (2005) Patients exposed to rofecoxib and celecoxib have different odds of nonfatal myocardial infarction. Ann Intern Med 142:157–164

    CAS  PubMed  Google Scholar 

  • King MC, Wieand S, Hale K et al (2001) National surgical adjuvant breast and bowel project tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: national surgical adjuvant breast and bowel project (NSABP-P1) breast cancer prevention trial. JAMA 286:2251–2256

    CAS  PubMed  Google Scholar 

  • Koehne CH, Dubois RN (2004) COX-2 inhibition and colorectal cancer. Semin Oncol 3:12–21

    Google Scholar 

  • Kurth T, Glynn RJ, Walker AM et al (2003) Inhibition of clinical benefits on first myocardial infarction by nonsteroidal anti-inflammatory drugs. Circulation 108:1191–1195

    CAS  PubMed  Google Scholar 

  • Lai KC, Lam SK, Chu KM et al (2002) Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med 346:2033–2038

    CAS  PubMed  Google Scholar 

  • Laine L (2001) Approaches to nonsteroidal anti-inflammatory drug use in the high-risk patient. Gastroenterology 120:594–606

    CAS  PubMed  Google Scholar 

  • Lanas A, Scheiman J (2007) Low-dose aspirin and upper gastrointestinal damage: epidemiology, prevention and treatment. Curr Med Res Opin 23:163–173

    CAS  PubMed  Google Scholar 

  • Larsson S, Orsini N, Wolk A (2005) Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst 97:1679–1687

    PubMed  Google Scholar 

  • Lev-Ari S, Maimon Y, Strier L et al (2006) Down-regulation of prostaglandin E2 by curcumin is correlated with inhibition of cell growth and induction of apoptosis in human colon carcinoma cell lines. J Soc Integr Oncol 4:21–26

    PubMed  Google Scholar 

  • Lévesque LE, Brophy JM, Zhang B (2005) The risk for myocardial infarction with cyclooxygenase-2 inhibitors: A population study of elderly adults. Ann Internal Med 142:481–489

    Google Scholar 

  • Lin KJ, Hernandez-Diaz S, Garcia Rodriguez LA (2011) Acid suppressants reduce risk of gastrointestinal bleeding in patients on antithrombotic or anti-inflammatory therapy. Gastroenterology 141:71–79

    CAS  PubMed  Google Scholar 

  • Lipkin M, Newmark H (1985) Effect of added dietary calcium on colonic epithelial-cell proliferation in subjects at high risk for familial colonic cancer. N Engl J Med 313:1381–1384

    CAS  PubMed  Google Scholar 

  • Livio M, Del Maschio A, Cerletti C et al (1982) Indomethacin prevents the long-lasting inhibitory effect of aspirin on human platelet cyclo-oxygenase activity. Prostaglandins 23:787–796

    CAS  PubMed  Google Scholar 

  • MacDonald TM, Wei L (2003) Effect of ibuprofen on cardioprotective effect of aspirin. Lancet 361:573–574

    CAS  PubMed  Google Scholar 

  • Mamdani M, Rochon P, Juurlink D et al (2003) Effect of selective cyclooxygenase two inhibitors and naproxen on short-term risk of acute myocardial infarction in the elderly. Arch Intern Med 163:481–486

    CAS  PubMed  Google Scholar 

  • Massó González EL, Patrignani P et al (2010) Variability among nonsteroidal antiinflammatory drugs in risk of upper gastrointestinal bleeding. Arthritis Rheum 62:1592–1601

    PubMed  Google Scholar 

  • McGettigan P, Han P, Henry D (2006) Cyclooxygenase-2 inhibitors and coronary occlusion: exploring dose-response relationships. Br J Clin Pharmacol 62:358–365

    CAS  PubMed  Google Scholar 

  • McGettigan P, Henry D (2006) Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA 296:1633–1644

    CAS  PubMed  Google Scholar 

  • Nussmeier NA, Whelton AA, Brown MT et al (2005) Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 352:1081–1091

    CAS  PubMed  Google Scholar 

  • Oates JA (2011) Cardiovascular risk markers and mechanisms in targeting the COX pathway for colorectal cancer prevention. Cancer Prev Res 4:1145–1148

    CAS  Google Scholar 

  • Pan MR, Chang HC, Hung WC (2008) Non-steroidal anti-inflammatory drugs suppress the ERK signaling pathway via block of Ras/c-Raf interaction and activation of MAP kinase phosphatases. Cell Signal 20:1134–1141

    CAS  PubMed  Google Scholar 

  • Parkin DM, Pisani P, Ferlay J (1999) Global cancer statistics. CA Cancer J Clin 49:33–64

    CAS  PubMed  Google Scholar 

  • Patel TN, Goldberg KC (2004) Use of aspirin and ibuprofen compared with aspirin alone and the risk of myocardial infarction. Arch Intern Med 164:852–856

    CAS  PubMed  Google Scholar 

  • Patrignani P, Capone ML, Tacconelli S (2008a) NSAIDs and cardiovascular disease. Heart 94:395–397

    CAS  PubMed  Google Scholar 

  • Patrignani P, Tacconelli S, Capone ML (2008b) Risk management profile of etoricoxib: an example of personalized medicine. Ther Clin Risk Manage 4:983–997

    CAS  Google Scholar 

  • Patrignani P, Panara MR, Greco A et al (1994) Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases. J Pharmacol Exp Ther 271:1705–1712

    CAS  PubMed  Google Scholar 

  • Patrignani P, Sciulli MG, Manarini S et al (1999) COX-2 is not involved in thromboxane biosynthesis by activated human platelets. J Physiol Pharmacol 50:661–667

    CAS  PubMed  Google Scholar 

  • Patrono C, Baigent C, Hirsh J et al (2008) Antiplatelet drugs: American college of chest physicians evidence-based clinical practice guidelines (8th edn). Chest 133(6 Suppl):199S–233S

    CAS  PubMed  Google Scholar 

  • Patrono C, Ciabattoni G, Pinca E et al (1980) Low dose aspirin and inhibition of thromboxane B2 production in healthy subjects. Thromb Res 17:317–327

    CAS  PubMed  Google Scholar 

  • Rao CV, Reddy BS (2004) NSAIDs and chemoprevention. Curr Cancer Drug Targets 4:29–42

    CAS  PubMed  Google Scholar 

  • Ray W, Stein C, Hall K et al (2002) Non-steroidal anti-inflammatory drugs and the risk of serious coronary heart disease: an observational study. Lancet 359:118–123

    CAS  PubMed  Google Scholar 

  • Ray WA, Varas-Lorenzo C, Chung CP et al (2009) Cardiovascular risks of non-steroidal anti-inflammatory drugs in patients following hospitalization for serious coronary heart disease. Circ Cardiovasc Qual Outcomes 2:155–163

    Google Scholar 

  • Reilly IA, FitzGerald GA (1987) Inhibition of thromboxane formation in vivo and ex vivo: implications for therapy with platelet inhibitory drugs. Blood 69:180–186

    CAS  PubMed  Google Scholar 

  • Renda G, Tacconelli S, Capone ML et al (2006) Celecoxib, ibuprofen and the antiplatelet effect of aspirin in patients with osteoarthritis and ischemic heart disease. Clin Pharmacol Ther 80:264–274

    CAS  PubMed  Google Scholar 

  • Rhame E, Pilote L, LeLorier J (2002) Association between naproxen use and protection against acute myocardial infarction. Arch Intern Med 162:1111–1115

    Google Scholar 

  • Rigas B, Goldman IS, Levine L (1993) Altered eicosanoid levels in human colon cancer. J Lab Clin Med 122:518–523

    CAS  PubMed  Google Scholar 

  • Roumie CL, Mitchel EFJ, Kaltenbach L, Arbogast PG, Gideon P, Griffin MR et al (2008) Nonaspirin NSAIDs, cyclooxygenase 2 inhibitors, and the risk for stroke. Stroke 39:2037–2045

    CAS  PubMed  Google Scholar 

  • Schlienger R, Jick H, Meier C (2002) Use of nonsteroidal anti-inflammatory drugs and the risk of first-time acute myocardial infarction. Br J Clin Pharmacol 54:327–332

    CAS  PubMed  Google Scholar 

  • Sciulli MG, Filabozzi P, Tacconelli S et al (2005) Platelet activation in patients with colorectal cancer. Prostaglandin Leukot Essent Fatty Acid 72:79–83

    CAS  Google Scholar 

  • Sciulli MG, Seta F, Tacconelli S et al (2003) Effects of acetaminophen on constitutive and inducible prostanoid biosynthesis in human blood cells. Br J Pharmacol 138:634–641

    CAS  PubMed  Google Scholar 

  • Shiff SJ, Rigas B (1999) The role of cyclooxygenase inhibition in the antineoplastic effects of nonsteroidal antiinflammatory drugs (NSAIDs). J Exp Med 190:445–450

    CAS  PubMed  Google Scholar 

  • Silverstein FE, Faich G, Goldstein JL et al (2000) Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. JAMA 284:1247–1255

    CAS  PubMed  Google Scholar 

  • Simmons DL, Botting RM, Hla T (2004) Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev 56:387–437

    CAS  PubMed  Google Scholar 

  • Singh G, Mithal A, Triadafilopoulos G (2005) Both selective COX-2 inhibitors and non-selective NSAIDs increase the risk of acute myocardial infarction in patients with arthritis: selectivity is with the patient not the drug class. Ann Rheum Dis 64(suppl III):85–86

    Google Scholar 

  • Singh G, Wu O, Langhorne P, Madhok R (2006) Risk of acute myocardial infarction with nonselective non-steroidal anti-inflammatory drugs: a meta-analysis. Arthritis Res Ther 8:R153–R161

    PubMed  Google Scholar 

  • Sinicrope FA (2006) Targeting cyclooxygenase-2 for prevention and therapy of colorectal cancer. Mol Carcinog 45:447–454

    CAS  PubMed  Google Scholar 

  • Smyth EM, Grosser T, Wang M, Yu Y et al (2009) Prostanoids in health and disease. J Lipid Res 50(Suppl):S423–S428

    PubMed  Google Scholar 

  • Solomon D, Glynn R, Levin R (2002) Nonsteroidal anti-inflammatory drug use and acute myocardial infarction. Arch Intern Med 162:1099–1104

    CAS  PubMed  Google Scholar 

  • Solomon D, Schneeweiss S, Glynn R et al (2004) Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation 109:2068–2073

    CAS  PubMed  Google Scholar 

  • Solomon DH, Avorn J, Sturmer T et al (2006a) Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: high-risk subgroups and time course of risk. Arthritis Rheum 54:1378–1389

    CAS  PubMed  Google Scholar 

  • Solomon SD, McMurray JJ, Pfeffer MA et al (2005) Adenoma prevention with celecoxib (APC) study investigators. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 352:1071–1080

    CAS  PubMed  Google Scholar 

  • Solomon SD, Pfeffer MA, McMurray JJ et al (2006b) Effect of celecoxib on cardiovascular events and blood pressure in two trials for the prevention of colorectal adenomas. Circulation 114:1028–1035

    CAS  PubMed  Google Scholar 

  • Steering Committee of the Physicians’ Health Study Research Group (1989) 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 321:129–135

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Sturkenboom MCJM, Dieleman J, Verhamme K et al (2005) Cardiovascular events during use of COX-2 selective and non-selective NSAIDs. Pharmacoepidemiol Drug Saf 14:S57

    Google Scholar 

  • Suissa S, Bernatsky S, Hudson M (2006) Antirheumatic drug use and the risk of acute myocardial infarction. Arthritis Rheum 55:531–536

    CAS  PubMed  Google Scholar 

  • Thrift AG, McNeil JJ, Forbes A et al (1999) Risk of primary intracerebral haemorrhage associated with aspirin and non-steroidal anti-inflammatory drugs: case-control study. BMJ 318:759–764

    CAS  PubMed  Google Scholar 

  • Trock B, Lanza E, Greenwald P (1990) Dietary fiber, vegetables, and colon cancer: critical review and meta-analyses of the epidemiologic evidence. J Natl Cancer Inst 82:650–661

    CAS  PubMed  Google Scholar 

  • Vane R (1971) Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 31:250–260

    Google Scholar 

  • Varas-Lorenzo C, Castellsague J, Stang MR et al (2009) The use of selective cyclooxygenase-2 inhibitors and the risk of acute myocardial infarction in Saskatchewan, Canada. Pharmacoepidemiol Drug Saf 18:1016–1025

    CAS  PubMed  Google Scholar 

  • Velentgas P, West W, Cannuscio CC et al (2006) Cardiovascular risk of selective cyclooxygenase-2 inhibitors and other non-aspirin non-steroidal anti-inflammatory medications. Pharmacoepidemiol Drug Saf 15:641–652

    CAS  PubMed  Google Scholar 

  • Wactawski-Wende J, Kotchen JM, Anderson GL et al (2006) Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 354:684–696

    CAS  PubMed  Google Scholar 

  • Wang D, Dubois RN (2010a) Eicosanoids and cancer. Nat Rev Cancer 10:181–193

    CAS  PubMed  Google Scholar 

  • Wang D, Dubois RN (2010b) The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene 29:781–788

    CAS  PubMed  Google Scholar 

  • Watson D, Rhodes T, Holmes R (2002) Lower risk of thromboembolic cardiovascular events with naproxen among patients with rheumatoid arthritis. Arch Intern Med 162:1105–1110

    CAS  PubMed  Google Scholar 

  • Weir HK, Thun MJ, Hankey BF et al (2003) Annual report to the nation on the status of cancer, 1975–2000, featuring the uses of surveillance data for cancer prevention and control. J Natl Cancer Inst 95:1276–1299

    PubMed  Google Scholar 

  • Willett WC, Stampfer MJ, Colditz GA et al (1990) Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. N Engl J Med 323:1664–1672

    CAS  PubMed  Google Scholar 

  • Wu K, Willett WC, Fuchs CS et al (2002) Calcium intake and risk of colon cancer in women and men. J Natl Cancer Inst 94:437–446

    PubMed  Google Scholar 

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Acknowledgments

This work was supported by research founding from the European Community Sixth Framework Programme (Eicosanox grant LSMH-CT-2004-005033). We apologize to our colleagues for not being able to reference all primary work due to space limitations.

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Authors and Affiliations

  1. Centro Español de Investigacion Farmacoepidemiologica (CEIFE), 2 Almirante 28, 28004 Madrid, Spain

    Luis A. Garcia Rodriguez & Lucia Cea-Soriano

  2. Center of Excellence On Aging (CeSI) and Department of Neuroscience and Imaging, G. d’Annunzio University, School of Medicine, Via dei Vestini 31, 66100 Chieti CH, Italy

    Stefania Tacconelli & Paola Patrignani

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  1. Luis A. Garcia Rodriguez
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  2. Lucia Cea-Soriano
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  3. Stefania Tacconelli
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  4. Paola Patrignani
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Correspondence to Luis A. Garcia Rodriguez or Paola Patrignani .

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Editors and Affiliations

  1. Massachusetts General Hospital, Gastrointestinal Unit, Harvard Medical School, Fruit Street 55, Boston, 02114, Massachusetts, USA

    Andrew T. Chan

  2. BSP-GD-GMA-CVRM, Berlin, S101, 09, 140, Bayer Schering Pharma AG, Müllerstraße 178, Berlin, 13351, Germany

    Elmar Detering

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Garcia Rodriguez, L.A., Cea-Soriano, L., Tacconelli, S., Patrignani, P. (2013). Coxibs: Pharmacology, Toxicity and Efficacy in Cancer Clinical Trials. In: Chan, A., Detering, E. (eds) Prospects for Chemoprevention of Colorectal Neoplasia. Recent Results in Cancer Research, vol 191. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30331-9_4

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