Prospective, double-blind, placebo-controlled, multicenter, randomized phase III study with orally administered budesonide for prevention of irinotecan (CPT-11)-induced diarrhea in patients with advanced colorectal cancer
Prospective, double-blind, placebo-controlled, multicenter, randomized phase III study with orally administered budesonide for prevention of irinotecan (CPT-11)-induced diarrhea in patients with advanced colorectal cancer
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DOI：
10.1159/000086971
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发表时间：
2005-01-01
期刊：
影响因子：
3.5
通讯作者：
Kleeberg, U
中科院分区：
文献类型：
--
作者：
Karthaus, M;Ballo, H;Kleeberg, U
背景：在伊立替康（CPT-11）治疗的患者中，不可预测的和严重的腹泻（NCl级bbb3）仍然是危及生命的不良事件。本研究的目的是评估口服布地奈德预防晚期结直肠癌患者cpt -11诱导的延迟性腹泻的有效性和安全性。患者和方法：共有56例接受CPT-11治疗（125 mg/m(2)，每周1次）的晚期结直肠癌患者入组了这项多中心试验。患者随机接受3毫克布地奈德口服治疗，每日3次，对照组为安慰剂。通过记录日记监测大便次数、大便一致性和洛哌丁胺抢救用药，详细评估腹泻情况。结果：在研究期间，58.3%的布地奈德治疗组患者可以预防腹泻（定义为每天发生的大便数量），而安慰剂组患者的这一比例为38.5%。布地奈德组患者发作次数较少（0.7次vs 2.2次），总腹泻持续时间明显短于安慰剂组（1.8天vs 4.2天）。安慰剂组洛哌丁胺的使用频率高于布地奈德组（55.6%对41.7%）。此外，安慰剂组（36.2粒）比布地奈德组（24.9粒）暴露于洛哌丁胺抢救药物的剂量更高。与安慰剂相比，布地奈德在第一个周期中对腹泻的预防效果更好（14 vs 10; p = 0.257），安慰剂组观察到更多的失败（16vs. 10）。10)。结论：这项双盲随机试验未能显示布地奈德在预防cpt -11诱导的腹泻方面有显著的益处。虽然存在这种趋势，但仍有必要进行进一步的试验。版权所有(C) 2005 S. Karger AG，巴塞尔。
Background: Unpredictable and severe diarrhea (NCl grade > 3) remains a life-threatening adverse event in patients treated with irinotecan (CPT-11). The aim of this study was to evaluate the efficacy and safety of orally administered budesonide for prevention of CPT-11-induced delayed diarrhea in patients with advanced colorectal cancer. Patients and Methods: A total of 56 patients with advanced colorectal cancer receiving CPT-11 therapy (125 mg/m(2) once weekly) were enrolled in this multicenter trial. Patients were randomly treated with 3 mg budesonide orally 3 times daily versus placebo. Detailed assessment of diarrhea by monitoring stool frequency, stool consistency and loperamide rescue medication was made by keeping a diary. Results: Diarrhea, defined as number of stools >4 occurring on a single day during the study period, could be prevented in 58.3% of the budesonide-treated patients compared to 38.5% of the patients under placebo. Patients in the budesonide group had less episodes (0.7 vs. 2.2 episodes) and a considerably shorter total duration of diarrhea (1.8 vs. 4.2 days) episodes than patients in the placebo group. Loperamide use was more frequent in the placebo than in the budesonide arm (55.6 vs. 41.7%). Also, exposure to rescue medication of loperamide was higher for placebo (36.2 capsules) than for budesonide (24.9 capsules). A superior prevention of diarrhea was observed for budesonide compared to placebo in the first cycle (14 vs. 10; p = 0.257), with more failures observed in the placebo group (16vs. 10). Conclusion:This double-blind randomized trial failed to show that budesonide has a significant benefit in preventing CPT-11-induced diarrhea. While a trend exists, further trials are warranted. Copyright (C) 2005 S. Karger AG, Basel.