Prevention by Aspirin of Colorectal Adenoma Recurrence: Some Advances and Latest Results of the APACC Trial

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• 作者：Robert Benamouzig (1)
  Bernard Uzzan (2)
  Jacques Deyra (3)
  Antoine Martin (4)
  Stanislas Chaussade (5)
  
• 关键词：Colorectal adenoma ; Chemoprevention ; Acetylsalicylic acid ; Randomized controlled trial ; Placebo ; COX ; 2 expression
• 刊名：Current Colorectal Cancer Reports
• 出版年：2011
• 出版时间：March 2011
• 年：2011
• 卷：7
• 期：1
• 页码：33-41
• 全文大小：273KB
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• 作者单位：Robert Benamouzig (1)
  Bernard Uzzan (2)
  Jacques Deyra (3)
  Antoine Martin (4)
  Stanislas Chaussade (5)
  
  1. Department of Gastroenterology, AP-HP, Avicenne Hospital, 125 route de Stalingrad, Paris-13 University, 93009, Bobigny, France
  2. Department of Pharmacology, AP-HP, Avicenne Hospital, 125 route de Stalingrad, Paris-13 University, 93009, Bobigny, France
  3. APACC, AP-HP, Cochin Hospital, 27 rue du Faubourg Saint-Jacques, Paris-5 University, 75679, Paris Cedex 14, France
  4. Department of Pathology, AP-HP, Avicenne Hospital, 125 route de Stalingrad, Paris-13 University, 93009, Bobigny, France
  5. Department of Gastroenterology, AP-HP, Cochin Hospital, 27 rue du Faubourg Saint-Jacques, Paris-5 University, 75679, Paris Cedex 14, France
  

文摘

In a randomized controlled trial (RCT), 272 patients were assigned to lysine acetylsalicylate 160?mg/day (n--3) or 300?mg/day (n--7) or placebo (n--32). The primary end points were adenoma recurrence and adenomatous polyp burden (APB) at year 1 or 4 (last colonoscopy) and at year 4. At last colonoscopy, APB tended to be lower under aspirin 160?mg or at either dose compared with placebo (P--.06 and 0.07, respectively). At year 4, 55 patients had received aspirin 160?mg/d, 47,300?mg/d, and 83 placebo. APB and proportions of patients with at least one recurrent adenoma were similar in both groups. A personal history of adenomas and an initial APB higher than 10?mm predicted recurrence. Among 219 adenomas from 136 patients, 128 adenomas (58%) from 59 patients strongly expressed COX-2 assessed by immunohistochemistry, mainly adenomas larger than 10?mm (84/129 vs 44/90; P--.02) and adenomas showing high-grade dysplasia (22/29 vs 104/188; P--.04). Deep stromal initial expression of COX-2 predicted recurrence (P--.04). Protection by aspirin was mainly observed in patients in whom COX-2 initial expression was low (RR: 0.59; 95% CI--.39-.90; P--.02). Aspirin decreased adenoma recurrence significantly at 1?year, marginally at year 1 or 4, and not at year 4, possibly due to attrition but also to a differential effect according to polyp natural history. In a recent patient-level meta-analysis including the four published RCTs, aspirin significantly decreased adenoma risk by 17% and risk of advanced lesions by 28%.