Effect of chemoprevention by low-dose aspirin of new or recurrent colorectal adenomas in patients with Lynch syndrome (AAS-Lynch): study protocol for a multicenter, double-blind, placebo-controlled randomized controlled trial

Adil Soualy, David Deutsch, Mourad Benallaoua, Amal Ait-Omar, Florence Mary, Sabine Helfen, Marouane Boubaya, Vincent Levy, Robert Benamouzig, AAS-Lynch group, Robert Benamouzig, Florence Mary, Amal Aït Omar, Mourad Benallaoua, Sabine Helfen, Semaher Al-Khafaji, Noémie Demare, Géraldine Perkins, Pierre Laurent-Puig, Jean-Christophe Saurin, Naouele Raby, Laurence Venat-Bouvet, Corinne Penaud, Delphine Bonnet, Virginie Sicart, Chloé Pomes, Thierry Lecomte, Claire Jollivet, Morgane Caulet, Stanislas Chaussade, Marion Dhooge, Fanny Maksimovic, Philippe Grandval, Sylvie Olschwang, Maud Saussereau, Jérôme Bellanger, Anne Netter-Coti, Hélène Delhomelle, Bruno Buecher, Lydia Mehdi, Sophie Lejeune, Afane Brahimi, Stéphane Cattan, Laurence Bellengier, David Tougeron, Sandrine Rafert, Emmanuelle Barouk Simonet, François Cornelis, Anna Serova-Erard, David Malka, Paul Gesta, Jeanne Oddoz, Véronique Mari, Samuel Lesourd, Gaëlle Kergoat, Louise Crivelli, Iradj Sobhani, Aurélien Amiot, Côme Lepage, Laurence Faivre-Olivier, Jean-Louis Jouve, Antoine Drouillard, Nora Perot, Marc Bardou, Sophie Nambot, Nadia Mekahli, Alain Lortholary, Carole Lenne, Jean-Paul Lagasse, Brahim Ouahrani, Thierry Frebourg, Nathalie Parodi, Maud Branchaud, Françoise Desseigne, Elodie Grinand, Olivier Ingster, Benoit Semelin, Francine Fein, Nelson Lourenco, Thomas Aparicio, Mathilde Brasseur, Anthony Lopez, Adil Soualy, David Deutsch, Mourad Benallaoua, Amal Ait-Omar, Florence Mary, Sabine Helfen, Marouane Boubaya, Vincent Levy, Robert Benamouzig, AAS-Lynch group, Robert Benamouzig, Florence Mary, Amal Aït Omar, Mourad Benallaoua, Sabine Helfen, Semaher Al-Khafaji, Noémie Demare, Géraldine Perkins, Pierre Laurent-Puig, Jean-Christophe Saurin, Naouele Raby, Laurence Venat-Bouvet, Corinne Penaud, Delphine Bonnet, Virginie Sicart, Chloé Pomes, Thierry Lecomte, Claire Jollivet, Morgane Caulet, Stanislas Chaussade, Marion Dhooge, Fanny Maksimovic, Philippe Grandval, Sylvie Olschwang, Maud Saussereau, Jérôme Bellanger, Anne Netter-Coti, Hélène Delhomelle, Bruno Buecher, Lydia Mehdi, Sophie Lejeune, Afane Brahimi, Stéphane Cattan, Laurence Bellengier, David Tougeron, Sandrine Rafert, Emmanuelle Barouk Simonet, François Cornelis, Anna Serova-Erard, David Malka, Paul Gesta, Jeanne Oddoz, Véronique Mari, Samuel Lesourd, Gaëlle Kergoat, Louise Crivelli, Iradj Sobhani, Aurélien Amiot, Côme Lepage, Laurence Faivre-Olivier, Jean-Louis Jouve, Antoine Drouillard, Nora Perot, Marc Bardou, Sophie Nambot, Nadia Mekahli, Alain Lortholary, Carole Lenne, Jean-Paul Lagasse, Brahim Ouahrani, Thierry Frebourg, Nathalie Parodi, Maud Branchaud, Françoise Desseigne, Elodie Grinand, Olivier Ingster, Benoit Semelin, Francine Fein, Nelson Lourenco, Thomas Aparicio, Mathilde Brasseur, Anthony Lopez

Abstract

Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC) and confers a high lifetime risk of CRC estimated to be up to 60%. Colonoscopy is recommended every 2 years in LS patients above the 20-25-year-old age bracket, and every year when colonic neoplasia has been detected. Efficient chemoprevention has the potential to represent a cost-effective intervention in these high-risk patients and could allow a delay in colonoscopy surveillance. Several epidemiological studies have shown that regular use of low dose aspirin is associated with a 20 to 30% reduction in the risk of sporadic colonic adenomas and colorectal cancer regardless of family risk. However, in recent large randomized trials in specific populations, aspirin use showed no protection for colorectal cancer. A prospective randomized CAPP-2 trial evaluated the effect of aspirin use in LS patients. The primary analysis of this trial showed no significant decrease in CRC in LS patients under daily aspirin. However, a preplanned secondary analysis after an extended follow-up showed a significant reduced risk of CRC in the aspirin group in the per-protocol analysis. The real effect and clinical benefit of aspirin are still to be consolidated in this population. The AAS-Lynch trial-a prospective, multicentric, double-blind, placebo-controlled, randomized clinical trial-was designed to investigate if daily aspirin therapy, at a dose of 100 or 300 mg, would decrease the occurrence or recurrence of colorectal adenomas in patients under 75 years of age, compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov NCT02813824 . Registered on 27 June 2016. The trial was prospectively registered.

Conflict of interest statement

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analysis, or interpretation of data; and in the writing of the manuscript.

References

    1. Vasen HFA, et al. One to 2-year surveillance intervals reduce risk of colorectal cancer in families with lynch syndrome. Gastroenterology. 2010;138:2300–2306. doi: 10.1053/j.gastro.2010.02.053.
    1. Chan AT, Ogino S, Fuchs CS. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med. 2007;356:2131–2142. doi: 10.1056/NEJMoa067208.
    1. Rothwell PM, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet. 2010;376:1741–1750. doi: 10.1016/S0140-6736(10)61543-7.
    1. Baron JA, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med. 2003;348:891–899. doi: 10.1056/NEJMoa021735.
    1. Sandler RS, 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. doi: 10.1056/NEJMoa021633.
    1. Logan RFA, et al. Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology. 2008;134:29–38. doi: 10.1053/j.gastro.2007.10.014.
    1. Pommergaard H-C, Burcharth J, Rosenberg J, Raskov H. Aspirin, calcitriol, and calcium do not prevent adenoma recurrence in a randomized controlled trial. Gastroenterology. 2016;150:114–122.e4. doi: 10.1053/j.gastro.2015.09.010.
    1. Benamouzig R, et al. Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial. Gastroenterology. 2003;125:328–336. doi: 10.1016/S0016-5085(03)00887-4.
    1. Hull MA, Sprange K, Hepburn T, et al. Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial. Lancet. 2018;392(10164):2583–2594. doi: 10.1016/S0140-6736(18)31775-6.
    1. Ishikawa H, et al. The preventive effects of low-dose enteric-coated aspirin tablets on the development of colorectal tumours in Asian patients: a randomised trial. Gut. 2014;63:1755–1759. doi: 10.1136/gutjnl-2013-305827.
    1. Cole BF, et al. Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. JNCI J Natl Cancer Inst. 2009;101:256–266. doi: 10.1093/jnci/djn485.
    1. Sutcliffe P, et al. Aspirin for prophylactic use in the primary prevention of cardiovascular disease and cancer: a systematic review and overview of reviews. Health Technol Assess Winch Engl. 2013;17:1–253.
    1. The ASCEND Study Collaborative Group Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med. 2018;379:1529–1539. doi: 10.1056/NEJMoa1804988.
    1. McNeil JJ, et al. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med. 2018;379:1519–1528. doi: 10.1056/NEJMoa1803955.
    1. Burn J, Bishop DT, Mecklin JP, et al. Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome [published correction appears in N Engl J Med. 2009 Apr 2;360(14):1470]. N Engl J Med. 2008;359(24):2567–78. 10.1056/NEJMoa0801297.
    1. Burn J, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet Lond Engl. 2011;378:2081–2087. doi: 10.1016/S0140-6736(11)61049-0.
    1. Järvinen HJ, et al. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology. 2000;118:829–834. doi: 10.1016/S0016-5085(00)70168-5.
    1. Rahmi G, et al. Impact of chromoscopy on adenoma detection in patients with Lynch syndrome: a prospective, multicenter, blinded, tandem colonoscopy study. Am J Gastroenterol. 2015;110:288–298. doi: 10.1038/ajg.2014.423.
    1. Bernardini D, Lapuelle J, Chaussade S, Robaszkiewicz M. Critères de qualité du compte rendu de coloscopie – Recommandations du CNP-HGE et de la SFED. Hépato-Gastro Oncol Digest. 2019;26(1):29–33. doi: 10.1684/hpg.2018.1732.
    1. Hercberg S, et al. The SU.VI.MAX study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004;164:2335–2342. doi: 10.1001/archinte.164.21.2335.
    1. Golubic R, et al. Validity of electronically administered recent physical activity questionnaire (RPAQ) in ten European countries. PLoS One. 2014;9(3):e92829. doi: 10.1371/journal.pone.0092829.
    1. Patrignani P, Patrono C. Aspirin, platelet inhibition and cancer prevention. Platelets. 2018;29:779–785. doi: 10.1080/09537104.2018.1492105.
    1. Dovizio M, Bruno A, Tacconelli S, Patrignani P. Mode of action of aspirin as a chemopreventive agent. Recent Results Cancer Res. 2013;191:39–65. doi: 10.1007/978-3-642-30331-9_3.
    1. Chan AT, McNeil J. Aspirin and cancer prevention in the elderly: where do we go from here? Gastroenterology. 2019;156(3):534–538. doi: 10.1053/j.gastro.2018.11.063.
    1. Fanaroff AC, Roe MT. Contemporary reflections on the safety of long-term aspirin treatment for the secondary prevention of cardiovascular disease. Drug Saf. 2016;39:715–727. doi: 10.1007/s40264-016-0421-1.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する