Is aspirin ready for colorectal cancer chemoprevention and adjuvant therapy?
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1 Is aspirin ready for colorectal cancer chemoprevention and adjuvant therapy? Robert Benamouzig Service de Gastroentérologie Hôpital Avicenne Bobigny, France
2 Aspirin and Colorectal carcinogenesis Aspirin inhibits: Animal experiments colon cancer xenograft in mouse model chemically-induced colonic carcinogenesis in rodents carcinogenesis related to APC gene mutations in the Min mouse model and APC (delta 474 ) mice
3 Aspirin and Colorectal carcinogenesis Animal experiments Number of animals with tumors Number of tumors per animal Early step of carcinogenesis: Aberrant crypt foci Before and after carcinogen administration Low and high dose Reversible
4 Colorectal cancer & aspirin : Case-control studies OR = cases
5 Colorectal cancer & aspirin : Cohort studies OR = cases
6 Aspirin RCTs : adenomas Cole, JNCI 2009
7 Aspirin vascular RCTs : Colorectal cancer -24% -35% Rothwell, Lancet 2010
8 Lynch & aspirin : CAPP2 600 mg per day during 29 months Burn, NEJM 2008 & Lancet 2011
9 Cancer Aspirin & other cancers Case-control and cohort studies Studies (n) Cases (n) RR 95% CI Oesophagus (SCC) Oesophagus/cardia (AdenoK) Gastric Pancreas Lung Endometrial Breast Ovarian Prostate Bladder Kidney
10 Aspirin RCTs : all cancer mortality -21% Rothwell, Lancet 2011
11 RCTs : all cancer mortality Secondary prevention Mills et al, 2012
12 RCTs : vascular and all cancer mortality Primary prevention Sheshasai et al, 2012 Significant bleeding every 73 persons
13 Adjuvant aspirin after colorectal cancer in patients : overall mortality Bastiaannet et al, Br J Cancer 2012
14 Adjuvant aspirin after colorectal cancer in patients > 70 years Reimers et al, 2013
15 Adjuvant aspirin in colorectal cancer : a PI3K mutation effect Liao et al, NEJM 2012
16 Major aspirin safety issues GI ulcers GI Bleeding + Significant GI bleeding : HR = 1.55 (CI ) 1 to 2 significant bleeds / 1000 person-years Lower risk for low dose aspirin? Intracranial bleeding ++ HR = 1.43 (CI ) 1 or 2 / person-years
17 Risk-benefit issues Hypothesis : 10% reduction in cancer mortality years Females years yearsmales Males years Thun et al, 2012
18 Is aspirin protection predated by endoscopy? Benefit for a cohort of subjects included in 20 years prevention programmes No screening Aspirin Sigmoidoscopy Sigmoidoscopy + Aspirin Colonoscopy Colonoscopy + Aspirin CRC cases CRC prevent. rate CRC deaths Lifeyears gained 35% 31% 58% 68% 78% Hassane et al, Gut 2012
19 Is aspirin protection predated by endoscopy? Hassane et al, Gut 2012
20 Colorectal cancer chemoprevention Aspirin is effective Aspirin is efficient Modalities & targets?
21 Aspirin Dose in RCTs Low dose better? Rothwell, Lancet 2010
22 Aspirin Dose in RCTs Low dose better? Cole, JNCI 2009
23 How long to treat: A long term effect 2 RR 1 Giovanucci, NEJM > 20 Duration of regular aspirin use
24 Aspirin prevention modalities? Dose Treatment duration Yes : the lower ( mg) Yes : the longest possible Target population Primary prevention?? Secondary prevention High risk (genetic)? High risk (non genetic)
25 Aspirin targets Discussed on a personal basis in : Healthy people with increased vascular risk 10 year risk > 10% Healthy people with increased cancer risk People with vascular conditions People with advanced colorectal adenomas, particularly those with proximal lesions
26 «Standard risk»? Age Sex BMI Exercice Diet Tobacco Vascular risk factors
27
28 Aspirin effect in high risk patients Reductions in colon cancer risk associated with aspirin use were not significantly modified by : Body mass index Physical activity Plasma C-peptide level Zhang et al, Am J Epidemiol 2011
29 Adjuvant aspirin after colorectal cancer To be considered PI3K mutation
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