Steinbach G, Lynch P M, Phillips R K, Wallace M H, Hawk E, Gordon G B, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su L K, Levin B, Godio L, Patterson S, Rodriguez-Bigas M A, Jester S L, King K L, Schumacher M, Abbruzzese J, DuBois R N, Hittelman W N, Zimmerman S, Sherman J W, Kelloff G
University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
N Engl J Med. 2000 Jun 29;342(26):1946-52. doi: 10.1056/NEJM200006293422603.
Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive effects of nonsteroidal antiinflammatory drugs may be related to their inhibition of cyclooxygenase-2.
We studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyps in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, we randomly assigned 77 patients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of the study. We determined the number and size of polyps from photographs and videotapes; the response to treatment was expressed as the mean percent change from base line.
At base line, the mean (+/-SD) number of polyps in focal areas where polyps were counted was 15.5+/-13.4 in the 15 patients assigned to placebo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the patients receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P=0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of polyp diameters) (P=0.001), as compared with reductions of 4.5 and 4.9 percent, respectively, in the placebo group. The improvement in the extent of colorectal polyposis in the group receiving 400 mg twice a day was confirmed by a panel of endoscopists who reviewed the videotapes. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9 percent (P=0.33 for the comparison with placebo) and 14.6 percent (P=0.09), respectively. The incidence of adverse events was similar among the groups.
In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibitor, leads to a significant reduction in the number of colorectal polyps.
家族性腺瘤性息肉病患者患结直肠癌的风险接近100%。在这种疾病中，非甾体抗炎药的化学预防作用可能与其对环氧化酶-2的抑制作用有关。
我们研究了选择性环氧化酶-2抑制剂塞来昔布对家族性腺瘤性息肉病患者结直肠息肉的影响。在一项双盲、安慰剂对照研究中，我们将77例患者随机分为接受塞来昔布（100或400mg，每日两次）或安慰剂治疗6个月。患者在研究开始和结束时接受内镜检查。我们从照片和录像带中确定息肉的数量和大小；治疗反应以相对于基线的平均变化百分比表示。
在基线时，在对息肉进行计数的局部区域，分配到安慰剂组的15例患者息肉的平均（±标准差）数量为15.5±13.4个，分配到每日两次服用100mg塞来昔布的32例患者为11.5±8.5个，分配到每日两次服用400mg塞来昔布的30例患者为12.3±8.2个（组间比较P = 0.66）。6个月后，每日两次服用400mg塞来昔布的患者结直肠息肉的平均数量减少了28.0%（与安慰剂组比较P = 0.003），息肉负担（息肉直径总和）减少了30.7%（P = 0.001），而安慰剂组分别减少了4.5%和4.9%。一组内镜医师通过查看录像带证实了每日两次服用400mg塞来昔布组结直肠息肉病程度的改善。每日两次服用100mg塞来昔布组的减少幅度分别为11.9%（与安慰剂组比较P = 0.33）和14.6%（P = 0.09）。各组不良事件的发生率相似。
在家族性腺瘤性息肉病患者中，每日两次服用400mg环氧化酶-2抑制剂塞来昔布治疗6个月可使结直肠息肉数量显著减少。
