Vandetanib in patients with inoperable hepatocellular carcinoma: A phase II, randomized, double-blind, placebo-controlled study
Vandetanib in patients with inoperable hepatocellular carcinoma: A phase II, randomized, double-blind, placebo-controlled study
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DOI：
10.1016/j.jhep.2011.12.013
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发表时间：
2012-01-01
影响因子：
25.7
通讯作者：
Cheng, Ann-Lii
中科院分区：
文献类型：
--
作者：
Hsu, Chiun;Yang, Tsai-Sheng;Cheng, Ann-Lii
背景与目的：血管内皮生长因子受体 (VEGFR) 和表皮生长因子受体 (EGFR) 抑制剂已在晚期肝细胞癌 (HCC) 中显示出抗肿瘤活性。本研究评估了凡德他尼（VEGFR 和 EGFR 的口服抑制剂）在不可切除的晚期 HCC 患者中的疗效和安全性。方法：符合条件的患者按 1:1:1 随机分配接受凡德他尼 300 mg/天、凡德他尼 100 mg/天或安慰剂。疾病进展后，所有患者都可以选择接受开放标签凡德他尼 300 mg/天。主要目的是评估肿瘤稳定率（完全缓解+部分缓解+疾病稳定> = 4个月）。次要评估包括无进展生存期（PFS）、总生存期（OS）和安全性。生物标志物研究包括循环促血管生成因子和动态对比增强磁共振成像 (DCE-MRI)。 结果：67 名患者被随机分为凡德他尼 300 mg (n = 19)、凡德他尼 100 mg (n = 25) 或安慰剂 (n = 23) 组。二十九名患者进入开放标签治疗。 Vandetanib 诱导循环 VEGF 显着增加并降低循环 VEGFR 水平。在凡德他尼组中，肿瘤稳定率与安慰剂没有显着差异：5.3%（凡德他尼 300 mg）、16.0%（凡德他尼 100 mg）和 8.7%（安慰剂）。凡德他尼治疗后，DCE-MRI 未检测到明显的血管变化。尽管发现凡德他尼治疗后 PFS 和 OS 有改善的趋势，但在统计学上并不显着。最常见的不良事件是腹泻和皮疹，其发生率在治疗组之间没有显着差异。结论：凡德他尼在 HCC 中的临床活性有限。安全性与之前的研究一致。 (C) 2012 年欧洲肝脏研究协会。由 Elsevier B.V. 出版。保留所有权利。
Background & Aims: Inhibitors of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) have shown anti-tumor activities in advanced hepatocellular carcinoma (HCC). The present study evaluated the efficacy and safety of vandetanib, an oral inhibitor of both VEGFR and EGFR, in patients with unresectable advanced HCC.Methods: Eligible patients were randomized 1:1:1 to receive vandetanib 300 mg/day, vandetanib 100 mg/day, or placebo. Upon disease progression, all patients had the option to receive open-label vandetanib 300 mg/day. The primary objective was to evaluate tumor stabilization rate (complete response + partial response + stable disease >= 4 months). Secondary assessments included progression-free survival (PFS), overall survival (OS) and safety. Biomarker studies included circulating pro-angiogenic factors and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).Results: Sixty-seven patients were randomized to vandetanib 300 mg (n = 19), vandetanib 100 mg (n = 25) or placebo (n = 23) groups. Twenty-nine patients entered open-label treatment. Vandetanib induced a significant increase in circulating VEGF and decrease in circulating VEGFR levels. In both vandetanib arms, tumor stabilization rate was not significantly different from placebo: 5.3% (vandetanib 300 mg), 16.0% (vandetanib 100 mg) and 8.7% (placebo). DCE-MRI did not detect significant vascular change after vandetanib treatment. Although trends of improved PFS and OS after vandetanib treatment were found, they were statistically insignificant. The most common adverse events were diarrhea and rash, whose incidence did not differ significantly between treatment groups.Conclusions: Vandetanib has limited clinical activity in HCC. The safety profile was consistent with previous studies. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.