Gastrointestinal perforation due to bevacizumab in colorectal cancer
Gastrointestinal perforation due to bevacizumab in colorectal cancer
复制标题
DOI：
10.1245/s10434-006-9337-9
复制
发表时间：
2007-06-01
影响因子：
3.7
通讯作者：
Salem, Ronald R.
中科院分区：
文献类型：
--
作者：
Saif, Muhammad Wasif;Elfiky, Aymen;Salem, Ronald R.
贝伐单抗是美国食品和药物协会批准的第一种血管内皮生长因子靶向药物，与标准化疗方案相结合，可大大提高转移性结直肠癌患者的无进展和总存活率。尽管贝伐单抗总体耐受性良好，但在临床试验中，一些患者发生了一些严重的不良事件，包括动脉血栓栓塞症和胃肠道穿孔。在关键的3期试验中首次观察到胃肠道穿孔，贝伐单抗组发生了6起事件(1.5%)，而对照组没有事件发生。从那时起，在其他大型试验中也观察到了类似的胃肠道穿孔率。典型的临床表现是伴随便秘和呕吐的腹痛。这样的事件发生在整个治疗过程中，与暴露时间无关。在有和没有消化性溃疡疾病、憩室病和长期使用非类固醇抗炎药病史的患者中，胃肠道穿孔的发生率没有差异。然而，原发肿瘤完好、近期乙状结肠镜检查或结肠镜检查病史、或既往辅助放射治疗的患者胃肠道穿孔的发生率似乎较高，但有必要通过多因素分析来证实这些初步发现。导致胃肠道穿孔的机制尚不清楚，可能是多因素的。发生胃肠道穿孔的患者应永久停用贝伐单抗。本文综述了贝伐单抗治疗结直肠癌患者胃肠道穿孔的发生率、临床表现、发病机制、危险因素及处理方法。
Bevacizumab is the first U.S. Food and Drug Association-approved vascular endothelial growth factor-targeted agent that greatly increases progression-free and overall survival in combination with standard chemotherapy regimens in patients with metastatic colorectal cancer. Although bevacizumab is generally well tolerated, some serious adverse events have occurred in some patients in clinical trials, including arterial thromboembolism and gastrointestinal (GI) perforation. GI perforation was first observed in the pivotal phase 3 trial, in which six events occurred in bevacizumab group (1.5%), compared with no events in the control group. Since then, similar rates of GI perforation have been observed in other large trials. Typical presentation was abdominal pain associated with constipation and vomiting. Such events occurred throughout treatment and were not correlated with duration of exposure. No difference in rate of GI perforations was found in patients who did and did not have a baseline history of peptic ulcer disease, diverticulosis, and history of chronic use of nonsteroidal anti-inflammatory drugs. However, the incidence of GI perforation seemed to be higher in patients with primary tumor intact, recent history of sigmoidoscopy or colonoscopy, or previous adjuvant radiotherapy, but it is necessary to confirm these preliminary findings by multivariate analyses. The mechanism responsible for causing GI perforation is not known and may be multifactorial. Bevacizumab should be permanently discontinued in patients who develop GI perforation. This article reviews the incidence, presentation, pathogenesis, risk factors, and management of GI perforation in patients with colorectal cancer who are treated with bevacizumab.