Saif Muhammad Wasif, Elfiky Aymen, Salem Ronald R
Yale Cancer Center, Yale University School of Medicine, Divisions of Medical and Surgical Oncology, 333 Cedar Street, FMP 116, New Haven, Connecticut 06520, USA.
Ann Surg Oncol. 2007 Jun;14(6):1860-9. doi: 10.1245/s10434-006-9337-9. Epub 2007 Mar 14.
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.
贝伐单抗是美国食品药品监督管理局批准的首个血管内皮生长因子靶向药物，在转移性结直肠癌患者中，与标准化疗方案联合使用时，可显著提高无进展生存期和总生存期。尽管贝伐单抗一般耐受性良好，但在临床试验中，部分患者出现了一些严重不良事件，包括动脉血栓栓塞和胃肠道穿孔。胃肠道穿孔首次在关键的3期试验中被观察到，在该试验中，贝伐单抗组发生了6例此类事件（1.5%），而对照组未发生。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发生率。典型表现为伴有便秘和呕吐的腹痛。此类事件在整个治疗过程中均有发生，且与暴露时间无关。有和没有消化性溃疡病、憩室病基线病史以及长期使用非甾体抗炎药病史的患者，胃肠道穿孔发生率无差异。然而，原发肿瘤完整、近期有乙状结肠镜或结肠镜检查史或既往有辅助放疗史的患者，胃肠道穿孔发生率似乎更高，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。本文综述了接受贝伐单抗治疗的结直肠癌患者胃肠道穿孔的发生率、表现、发病机制、危险因素及处理方法。
