Department of Gastroenterology and Oncology, Institutes of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Clin Cancer Res. 2011 Jun 1;17(11):3803-11. doi: 10.1158/1078-0432.CCR-10-2395. Epub 2011 Mar 8.
On the basis of the results of our preliminary trial suggesting that aberrant crypt foci (ACF) could be eradicated by short-term administration of sulindac, in the present study, we explored the feasibility of using ACF as surrogate markers for chemoprevention of colorectal cancer.
Randomly assigned to sulindac (300 mg daily), etodolac (400 mg daily), and placebo groups were 189 subjects without polyps or who had undergone polypectomy. Drugs were administered for 2 months. ACF in the rectal region were counted by magnifying endoscopy. Occurrence of polyps was evaluated at 12 months. A planned interim analysis was conducted.
ACF number at 2 months was significantly suppressed in the sulindac group (P = 0.0075), but not in the etodolac group (P = 0.73). In the sulindac group, the numbers of adenomas plus hyperplastic polyps (total polyps) and adenomas at 12 months were significantly (P = 0.02) and marginally (P = 0.064) lower, respectively, in comparison with the placebo group; no such difference was observed in the etodolac group. In analysis of only polypectomized subjects, the numbers of total polyps and adenomas in the sulindac group were even more markedly lower, with P values of 0.014 and 0.034, respectively. A similar tendency was confirmed by analyses of the incidence of polyps at 12 months. Suppression rates of total polyps and adenomas in ACF responders to sulindac were significantly greater than in nonresponders. In all groups, compliance was more than 90% and no intolerable adverse effects were observed.
ACF may be useful as surrogate lesions for chemoprevention of colorectal cancer.
基于我们的初步试验结果表明，短期应用舒林酸可以消除异常隐窝病灶（ACF），本研究旨在探索将 ACF 作为结直肠癌化学预防替代标志物的可行性。
189 例无息肉或息肉切除术患者随机分为舒林酸（300mg 每日）、依托度酸（400mg 每日）和安慰剂组。药物治疗 2 个月。通过放大内镜计数直肠区域的 ACF。12 个月时评估息肉发生情况。进行了计划的中期分析。
舒林酸组 2 个月时 ACF 数量明显减少（P=0.0075），而依托度酸组则无变化（P=0.73）。舒林酸组 12 个月时腺瘤加增生性息肉（总息肉）和腺瘤的数量明显（P=0.02）和边缘性（P=0.064）低于安慰剂组；依托度酸组则无差异。在仅对息肉切除术患者进行分析时，舒林酸组的总息肉和腺瘤数量下降更为明显，P 值分别为 0.014 和 0.034。在分析 12 个月时的息肉发生率时也证实了类似的趋势。对舒林酸有反应的 ACF 患者的总息肉和腺瘤抑制率明显大于无反应者。在所有组中，依从性均大于 90%，未观察到不可耐受的不良反应。
ACF 可能是结直肠癌化学预防的有用替代病变。
