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贝伐单抗对化疗所致肝毒性有保护作用吗?

[Does bevacizumab have a protective effect on hepatotoxicity induced by chemotherapy?].

作者信息

Zalinski S, Bigourdan J-M, Vauthey J-N

机构信息

Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.

出版信息

J Chir (Paris). 2010 Jan;147 Suppl 1:S18-24. doi: 10.1016/S0021-7697(10)70004-1.

Abstract

Although the prognosis of patients with colorectal liver metastases (CLM) has improved dramatically with oxaliplatin and irinotecan, the enthusiasm for the preoperative use of these cytotoxic agents is being tempered by concerns about their impact on the nontumoral liver parenchyma. Bevacizumab, an anti-angiogenic agent that specifically targets the vascular endothelial growth factor, exerts an antitumor effect by inhibiting the development of the vascular network that is promoted by the tumor and mandatory for its growth. Yet angiogenesis is also a physiologic event contributing to wound healing and tissue regeneration. To date, it is well documented that the use of bevacizumab in combination with cytotoxic agents greatly improves pathologic response. Also well described is the protective effect of bevacizumab against sinusoidal injuries induced by oxaliplatin-based chemotherapy. Up to now, no side effects related to the perioperative use of bevacizumab have been reported in the setting of liver resection for CLM, and bevacizumab was shown not to impair liver regeneration following portal vein embolization. The clinical consequences of the protective effect of bevacizumab against sinusoidal injuries are hard to evaluate as patient selection and preparation have improved and these improvements contribute greatly to the favorable outcomes following liver resection for CLM. Indeed, patient safety in the setting of hepatic resection for CLM mainly depends on a careful preoperative evaluation of liver volumes and a limited use of cytotoxic agents followed by a delay of at least 5 weeks before the surgery.

摘要

尽管随着奥沙利铂和伊立替康的应用,结直肠癌肝转移(CLM)患者的预后有了显著改善,但由于担心这些细胞毒性药物对非肿瘤性肝实质的影响,人们对术前使用它们的热情有所降温。贝伐单抗是一种特异性靶向血管内皮生长因子的抗血管生成药物,通过抑制肿瘤促进的、对其生长必不可少的血管网络的形成发挥抗肿瘤作用。然而,血管生成也是一个有助于伤口愈合和组织再生的生理过程。迄今为止,有充分的文献证明,贝伐单抗与细胞毒性药物联合使用可大大改善病理反应。贝伐单抗对基于奥沙利铂的化疗引起的肝血窦损伤的保护作用也有详细描述。到目前为止,在CLM肝切除术中,尚未有与围手术期使用贝伐单抗相关的副作用报道,并且贝伐单抗在门静脉栓塞后并未损害肝脏再生。由于患者选择和准备工作有所改善,这些改善对CLM肝切除术后的良好结果有很大贡献,因此很难评估贝伐单抗对肝血窦损伤的保护作用的临床后果。事实上,CLM肝切除术中的患者安全主要取决于术前对肝脏体积的仔细评估、细胞毒性药物的有限使用以及手术前至少延迟5周。

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