Saif M Wasif, Mehra Ranee
Yale University School of Medicine, Division of Medical Oncology, 333 Cedar Street, FMP 116, New Haven, CT 06520, USA.
Expert Opin Drug Saf. 2006 Jul;5(4):553-66. doi: 10.1517/14740338.5.4.553.
Bevacizumab, a recombinant, humanised monoclonal antibody against vascular endothelial growth factor, when used in combination with intravenous 5-fluorouracil (5-FU)-based chemotherapy as first-line treatment of metastatic colorectal cancer (CRC) improves survival. In a randomised, placebo-controlled Phase III study, the addition of bevacizumab to irinotecan/5-FU/leucovorin (IFL) resulted in significant improvement in survival compared with IFL alone, which led to its approval for first-line use in CRC. Bevacizumab also demonstrates improved efficacy in combination with 5-FU/LV over chemotherapy alone when data were pooled from two randomised Phase II studies utilising bevacizumab with 5-FU/leucovorin, and also in a third treatment arm of bevacizumab/5-FU/LV of a randomised Phase III study. More recently, in the second-line setting, bevacizumab in combination with FOLFOX improved survival from 10.8 to 12.9 months in the ECOG 3200 trial. Clinical activity with the addition of bevacizumab to oxaliplatin and either 5-FU or capecitabine-based regimens has also been shown in TREE-2, and activity with the combination of bevacizumab and the EGFR inhibitor cetuximab has been documented in BOND-2. In this study, bevacizumab was generally well-tolerated with no unexpected toxicities when combined with cetuximab. A few toxicities were uniformly encountered in all of the above studies, in particular grade 3 medically-manageable hypertension (3 - 16%). In addition, other toxicities were haemorrhage (2 - 9.3%), gastrointestinal perforation (1.5%), arterial thromboembolism (3.8%), wound healing (1 - 2%) and proteinuria (1 - 2%). As bevacizumab is becoming widely used in general oncology practice, it is important to understand the toxicities which can arise and to develop practice guidelines for their management. This review addresses the toxicities noted in trials using bevacizumab for the treatment of CRC and provides recommendations for toxicity management.
贝伐单抗是一种重组人源化单克隆抗体，可抗血管内皮生长因子，与基于静脉注射5-氟尿嘧啶（5-FU）的化疗联合用于转移性结直肠癌（CRC）的一线治疗时可提高生存率。在一项随机、安慰剂对照的III期研究中，与单纯使用伊立替康/5-FU/亚叶酸钙（IFL）相比，在IFL中添加贝伐单抗可显著提高生存率，这使其获批用于CRC的一线治疗。当汇总两项使用贝伐单抗联合5-FU/亚叶酸钙的随机II期研究以及一项随机III期研究的贝伐单抗/5-FU/亚叶酸钙治疗组的数据时，贝伐单抗与5-FU/LV联合使用也显示出比单纯化疗更高的疗效。最近，在二线治疗中，在ECOG 3200试验中，贝伐单抗联合FOLFOX可使生存期从10.8个月提高至12.9个月。在TREE-2研究中也显示了在奥沙利铂和基于5-FU或卡培他滨的方案中添加贝伐单抗的临床活性，并且在BOND-2研究中记录了贝伐单抗与表皮生长因子受体（EGFR）抑制剂西妥昔单抗联合使用的活性。在本研究中，贝伐单抗与西妥昔单抗联合使用时一般耐受性良好，未出现意外毒性。在上述所有研究中均一致出现了一些毒性，特别是3级可通过药物治疗的高血压（3%-16%）。此外，其他毒性包括出血（2%-9.3%）、胃肠道穿孔（1.5%）、动脉血栓栓塞（3.8%）、伤口愈合问题（1%-2%）和蛋白尿（1%-2%）。由于贝伐单抗在普通肿瘤学实践中应用越来越广泛，了解可能出现的毒性并制定其管理的实践指南很重要。本综述阐述了使用贝伐单抗治疗CRC的试验中所发现的毒性，并提供了毒性管理的建议。
