| 返回首页 | 新闻中心 | Celecoxib有效减少大肠腺瘤性息肉的发生率 |
|
|
| Celecoxib有效减少大肠腺瘤性息肉的发生率 | |
| 2008(加州圣地牙哥) — 没有潜在心血管疾病而有大肠腺瘤性息肉风险的病患，可以使用celecoxib进行安全且有效的预防；发表於美国癌症研究学会2008年会之第三期随机试验的五年资料显示，虽然COX-2 抑制剂在一些病患会引起增加心血管风险，但celecoxib 在减少腺瘤性息肉相当有效。 「Adenoma Prevention with Celecoxib (APC) 」试验的主要作者、波士顿布莱根妇女医院的外科副教授Monica Bertagnolli医师表示，有超过2,000名病患参加此研究，他们被分成三组，主要终点是评估三年的腺瘤性息肉发生率，但是我们希望可以维持到五年。 当研究人员发现可能有心臟毒性时停止了该项研究；当时，所有参与的病患几乎都接受治疗达三年，研究者决定将继续监测病患两年，以评估安全性和有效性。 APC研究将2,035名有发生偶发大肠腺瘤性息肉风险的病患随机分成以下三组：每天两次的 celecoxib 200 mg (总共400 mg)；每天两次的celecoxib 400 mg (总共800 mg)；或者安慰剂。三年结束时，服用400 mg celecoxib的病患中，33%有较少的腺瘤性息肉，且57%有较少的恶化病灶；服用800 mg celecoxib的病患，45%有较少的腺瘤性息肉，66%有较少的恶化病灶。 研究结束时，参与者可以选择继续两年的无治疗观察研究机会；五年之后，服用低剂量celecoxib的病患，其腺瘤性息肉率减少达41%，服用剂量celecoxib的病患则减少25%腺瘤性息肉率；在五年时，共有639名病患进行大肠镜，结果显示，服用400 mg celecoxib的累积恶化腺瘤性息肉发生率为0.125，服用800 mg者为0.158，服用安慰剂者为0.212。 Bertagnolli医师表示，我们有超过400病患-年的资料，这些病患都属於腺瘤性息肉高风险；服用安慰剂的病患有22%发生恶化腺瘤性息肉，许多有復发的腺瘤性息肉。 她也指出，研究中有84%的病患有至少一个心血管疾病风险；在我们设计研究的时候，我们不知道会有心血管风险，所以没有针对心臟病的排除规范。 整体而言，未校正的选择性心血管事件，据研究者报告，服用安慰剂的676名病患发生35件，服用低剂量celecoxib的683名病患发生45件，服用高剂量的669名病患发生46件。 Bertagnolli医师表示，有许多不同的方法来检视安全性；如果我们著眼於紧急治疗事件— 发生在第一次服用之后且持续到最后一次剂量— 佔整个心血管事件的8.5%；使用药物治疗的两组有比较多的事件，属一致的剂量反应。 研究开始时，有至少两个心血管风险因素的病患，在研究期间有最高的心臟併发症风险，这组中，服用 800 mg的病患有11.2%的风险，服用400 mg的病患有8.2%的风险，服用安慰剂的病患有5.9%的风险。 有三分之一的病患服用低剂量阿斯匹灵保护心臟，五年的大肠镜检查显示，这一小组病患的腺瘤性息肉发生率增加，显示使用阿斯匹灵者有比较恶化的疾病发生。 她结论表示，Celecoxib在降低腺瘤性息肉的有效率满高，在停止服用药物之后还可持续；服用较高剂量并无好处，每天两次、每次 200 mg比 400 mg安全，但是对於有心臟风险因素的病患来说，这两种剂量都不能说是安全的。 美国癌症研究学会(AACR) 2008年会：摘要LB-141。发表於2008年4月14日。 Celecoxib Effective in Reducing Incidence of Colon Adenomas April 16, 2008 (San Diego, California) — In patients without underlying cardiovascular disease who are at high risk for colon adenomas, chemoprevention with celecoxib appears to be safe and effective. The 5-year data from a randomized phase 3 trial, presented here at the American Association for Cancer Research 2008 Annual Meeting, found that although the COX-2 inhibitors have been associated with increased cardiovascular risk in some patients, celecoxib was highly effective in reducing adenomas. \"There were over 2000 patients enrolled in the study, with 3 treatment arms,\" said Monica Bertagnolli, MD, an associate professor of surgery at the Brigham and Women\'s Hospital, in Boston, Massachusetts, and the lead researcher on the Adenoma Prevention with Celecoxib (APC) trial. \"The main end point was to evaluate the incidence of adenomas at 3 years, but we wanted to keep it going for 5 years.\" The study was halted when the researchers became aware of associated cardiac toxicity. At that point, nearly all of the enrolled patients had received treatment for 3 years. The researchers decided that they would continue monitoring patients for an additional 2 years to assess safety and efficacy. The APC study randomized 2035 patients who were at high risk for developing sporadic colon adenomas into 1 of 3 groups: celecoxib 200 mg twice daily (total, 400 mg); celecoxib 400 mg twice daily (total, 800 mg); or placebo. At the 3-year end point, patients taking 400 mg of celecoxib had 33% fewer adenomas and 57% fewer advanced lesions. Participants taking the 800 mg dose had 45% fewer adenomas and 66% fewer advanced lesions. At the end of the study, participants were offered the opportunity to continue in a 2-year off-treatment observational study. After 5 years, the rate of adenomas was reduced by 41% in patients who took the lower dose of celecoxib, and by 25% in patients who took the higher dose. Colonoscopies were performed on 639 patients at 5 years, and results demonstrated a cumulative advanced adenoma incidence of 0.125 in patients who took 400 mg of celecoxib and 0.158 in patients who took 800 mg, compared with 0.212 in patients who took placebo. \"We had more than 400 patient-years of data,\" said Dr. Bertagnolli. \"These patients were all at very high risk for adenomas. Twenty-two percent of patients on placebo developed advanced adenomas, and many had recurring adenomas.\" She also pointed out that 84% of patients in the study had at least 1 risk factor for cardiovascular disease. \"At the time we designed it, we didn\'t know about the cardiovascular risk, so there was no exclusion criteria for heart disease.\" Overall, nonadjudicated selected cardiovascular events, as reported by trial investigators, occurred 35 times in the 676 patients taking placebo, 45 times in 683 patients taking the lower dose of celecoxib, and 46 times in 669 patients taking the higher dose. \"There are many different ways of looking at safety,\" said Dr. Bertagnolli. \"If we look at treatment-emergent events — an event that occurs after the first dose of the drug is taken and continues until the last dose — we saw that 8.5% had some type of adverse cardiovascular event. There were more events in the 2 groups that used the drug, and there was a consistent dose response.\" Patients who had at least 2 cardiovascular risk factors at study baseline were at the highest risk for cardiac complications during the course of the study. Among this subgroup, patients taking 800 mg had an 11.2% risk, those taking 400 mg had an 8.2% risk, and those taking placebo had a 5.9% risk. One third of the patients were taking low-dose aspirin for cardiac protection, and 5-year colonoscopy data showed that this subset had an increased incidence of adenomas, suggesting the presence of more aggressive disease in individuals using aspirin. \"Celecoxib had a high rate of efficacy for reducing adenomas, and it persists even after discontinuing the drug,\" she concluded. \"There was no benefit to the higher dose. The twice-daily 200 mg is safer than 400 mg, but we can\'t say that either dose is safe for a patient with cardiac risk factors.\" American Association for Cancer Research (AACR) 2008 Annual Meeting: Abstract LB-141. Presented April 14, 2008. 发布时间：2008年04月24日 |
|
| 【推荐好友】 【发表评论】 |