A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer
A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer
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DOI：
10.1056/nejmoa021491
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发表时间：
2003-07-31
影响因子：
158.5
通讯作者：
Rosenberg, SA
中科院分区：
文献类型：
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作者：
Yang, JC;Haworth, L;Rosenberg, SA
背景：肿瘤抑制基因VHL的突变导致肾透明细胞癌血管内皮生长因子的过度分泌。我们进行了一项临床试验，以评估贝伐单抗，血管内皮生长因子的中和抗体，在转移性renal cell carcinoma.METHODS：一个随机，双盲，2期试验进行比较安慰剂与贝伐单抗的剂量为3和10毫克每公斤体重，每两周给予一次;疾病进展的时间和反应率的主要终点。允许从安慰剂到抗体治疗的交叉，生存是次要终点。结果：观察到最小的毒性作用，以高血压和无症状蛋白尿为主。在中期分析符合提前停止标准后，停止试验。116名患者被随机分配到治疗组（安慰剂组40例，低剂量抗体组37例，高剂量抗体组39例），与安慰剂组相比，高剂量抗体组的疾病进展时间显著延长（风险比，2.55;所有比较的P0.20）。贝伐单抗可显著延长转移性肾细胞癌患者的疾病进展时间。
BACKGROUND:Mutations in the tumor-suppressor gene VHL cause oversecretion of vascular endothelial growth factor by clear-cell renal carcinomas. We conducted a clinical trial to evaluate bevacizumab, a neutralizing antibody against vascular endothelial growth factor, in patients with metastatic renal-cell carcinoma.METHODS:A randomized, double-blind, phase 2 trial was conducted comparing placebo with bevacizumab at doses of 3 and 10 mg per kilogram of body weight, given every two weeks; the time to progression of disease and the response rate were primary end points. Crossover from placebo to antibody treatment was allowed, and survival was a secondary end point.RESULTS:Minimal toxic effects were seen, with hypertension and asymptomatic proteinuria predominating. The trial was stopped after the interim analysis met the criteria for early stopping. With 116 patients randomly assigned to treatment groups (40 to placebo, 37 to low-dose antibody, and 39 to high-dose antibody), there was a significant prolongation of the time to progression of disease in the high-dose-antibody group as compared with the placebo group (hazard ratio, 2.55; P0.20 for all comparisons).CONCLUSIONS:Bevacizumab can significantly prolong the time to progression of disease in patients with metastatic renal-cell cancer.