Bevacizumab for Patients with Metastatic Renal Cancer
Bevacizumab for Patients with Metastatic Renal Cancer
复制标题
贝伐单抗用于转移性肾癌患者
作者：
J. Yang
大多数透明细胞肾细胞癌（RCC）是由von Hippel-Lindau基因的双等位基因丢失引起的。这种损失的一个后果是通过涉及缺氧诱导因子积累的途径上调血管内皮生长因子。血管内皮生长因子是一种有效的血管生成因子，由许多人类癌症分泌，但透明细胞RCC作为一个群体产生特别高的水平，并具有高度的血管组织学外观。在一项随机、安慰剂对照、双盲试验中，我们测试了血管内皮生长因子中和抗体贝伐单抗在转移性肾细胞癌患者中的应用。在每2周一次3或10 mg/kg剂量下，毒性作用极轻微，高血压和蛋白尿是最严重的事件。在接受较高剂量贝伐珠单抗的患者中，有4例部分缓解（缓解率10%），肿瘤进展时间显著延长。采用交叉设计和非常敏感的疾病进展标准，没有显示生存率差异。4例患者已接受长期贝伐珠单抗治疗3 - 5年，无肿瘤进展。三个有大量的蛋白尿，但保持正常的肾功能。一个小的试点试验结合贝伐单抗和沙利度胺显示没有意外的毒性作用。未来的试验应考虑联合治疗和策略，其中患者通过抗血管生成药物（如贝伐单抗）治疗初始疾病进展。
Most clear cell renal cell cancer (RCC) is caused by biallelic loss of the von Hippel-Lindau gene. One consequence of this loss is up-regulation of vascular endothelial growth factor via a pathway involving accumulation of hypoxia inducible factor. Vascular endothelial growth factor, a potent angiogenic factor, is secreted by many human cancers, but clear cell RCC as a group produces particularly high levels and has a highly vascular histologic appearance. In a randomized, placebo-controlled, double-blind trial, we tested the use of a neutralizing antibody to vascular endothelial growth factor, bevacizumab, in patients with metastatic RCC. At 3 or 10 mg/kg every 2 weeks, toxic effects were minimal, with hypertension and proteinuria the most substantial events. There were four partial responses (10% response rate) and a highly substantial prolongation of time to tumor progression in patients who received the higher dose of bevacizumab. With a crossover design and very sensitive criteria for disease progression, no difference in survival was shown. Four patients have been undergoing long-term bevacizumab therapy without tumor progression for 3 to 5 years. Three have substantial proteinuria but retain normal renal function. A small pilot trial combining bevacizumab and thalidomide showed no unexpected toxic effects. Future trials should consider combination therapies and strategies in which patients are treated through initial disease progression with antiangiogenic agents such as bevacizumab.
影响因子：
4
作者：
W. Plunkett;P. Huang;Y. Z. Xu;V. Heinemann;R. Grunewald;V. Gandhi
通讯作者：
W. Plunkett;P. Huang;Y. Z. Xu;V. Heinemann;R. Grunewald;V. Gandhi
影响因子：
158.5
作者：
Yang, JC;Haworth, L;Rosenberg, SA
通讯作者：
Rosenberg, SA