Departments of Oncology and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Division of Hematology and Oncology, Chang-Gung Memorial Hospital Linkou, Linkou, Taiwan.
J Hepatol. 2012 May;56(5):1097-1103. doi: 10.1016/j.jhep.2011.12.013. Epub 2012 Jan 13.
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.
Eligible patients were randomized 1:1:1 to receive vandetanib 300mg/day, vandetanib 100mg/day, or placebo. Upon disease progression, all patients had the option to receive open-label vandetanib 300mg/day. The primary objective was to evaluate tumor stabilization rate (complete response+partial response+stable disease ⩾4months). 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).
Sixty-seven patients were randomized to vandetanib 300mg (n=19), vandetanib 100mg (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 300mg), 16.0% (vandetanib 100mg) 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.
Vandetanib has limited clinical activity in HCC. The safety profile was consistent with previous studies.
血管内皮生长因子受体（VEGFR）和表皮生长因子受体（EGFR）抑制剂在晚期肝细胞癌（HCC）中显示出抗肿瘤活性。本研究评估了口服 VEGFR 和 EGFR 双重抑制剂凡德他尼在不可切除的晚期 HCC 患者中的疗效和安全性。
符合条件的患者以 1:1:1 的比例随机分配至凡德他尼 300mg/天、凡德他尼 100mg/天或安慰剂组。疾病进展后，所有患者均有选择接受开放标签凡德他尼 300mg/天治疗的机会。主要终点是评估肿瘤稳定率（完全缓解+部分缓解+稳定疾病≥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）。
67 例患者被随机分配至凡德他尼 300mg 组（n=19）、凡德他尼 100mg 组（n=25）或安慰剂组（n=23）。29 例患者进入开放标签治疗。凡德他尼诱导循环 VEGF 水平显著升高，循环 VEGFR 水平降低。在凡德他尼两个剂量组中，肿瘤稳定率与安慰剂组无显著差异：5.3%（凡德他尼 300mg）、16.0%（凡德他尼 100mg）和 8.7%（安慰剂）。DCE-MRI 未检测到凡德他尼治疗后血管明显变化。尽管发现凡德他尼治疗后 PFS 和 OS 有改善趋势，但无统计学意义。最常见的不良反应是腹泻和皮疹，各组之间的发生率无显著差异。
凡德他尼在 HCC 中临床活性有限。安全性与既往研究一致。
