Cediranib (AZD2171) in patients with advanced hepatocellular carcinoma: a phase II North Central Cancer Treatment Group Clinical Trial.
Cediranib (AZD2171) in patients with advanced hepatocellular carcinoma: a phase II North Central Cancer Treatment Group Clinical Trial.
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DOI：
10.1097/coc.0b013e3182118cdf
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发表时间：
2012-08
期刊：
影响因子：
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通讯作者：
Nair S
中科院分区：
文献类型：
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作者：
Alberts SR;Fitch TR;Kim GP;Morlan BW;Dakhil SR;Gross HM;Nair S
血管内皮生长因子（VEGF）在肝细胞癌（HCC）的一些研究中被证明是过表达的。Cediranib是一种有效的VEGF信号抑制剂。我们评估了cediranib在HCC患者中的疗效和毒性。28例不可切除或转移性HCC患者参加了这项研究。患者接受45 mg cediranib口服，每日1次，28天为一个周期。这项II期研究的主要目的是评估6个月的生存期。次要目的是评估肿瘤反应、进展时间和毒性。所有28例患者均可评估疗效结果。12例（42.9%）患者存活6个月，15例（53.6%）患者在6个月内死亡，1例（3.6%）患者6个月前失访。中位总生存期为5.8个月（95% CI: 3.4-7.3个月）。没有患者出现确诊的反应。中位进展时间为2.8个月（95% CI: 2.3 - 4.4个月）。26例患者（93%）出现3+级不良事件（AE），最常见的AE是疲劳（46%）、厌食症（25%）、高血压（21%）和谷丙转氨酶（ALT）升高（18%）。由于毒性，西地尼布在该剂量和方案下对不可切除或转移性HCC患者不是有效的治疗方法。
Vascular endothelial growth factor (VEGF) has been shown to be overexpressed in several studies of hepatocellular carcinoma (HCC). Cediranib is a potent inhibitor of VEGF signaling. We assessed the efficacy and toxicity of cediranib in patients with HCC. Twenty-eight patients with unresectable or metastatic HCC were enrolled on this study. Patients received 45 mg of cediranib orally, once daily, for 28 day cycles. The primary objective of this Phase II study was to assess six-month survival. Secondary objectives were to assess tumor response, time-to-progression, and toxicity. All 28 patients were evaluable for efficacy outcomes. Twelve patients (42.9%) survived 6 months, 15 (53.6%) died within 6 months, and one (3.6%) was lost to follow-up before 6 months. The median overall survival was 5.8 months (95% CI: 3.4–7.3 months). No patients experienced confirmed response. The median time-to-progression was 2.8 months (95% CI: 2.3 – 4.4 months). Twenty-six patients (93%) experienced a grade 3+ adverse event (AE) with the most common AEs being fatigue (46%), anorexia (25%), hypertension (21%), and elevated alanine aminotransferase (ALT) (18%). Due to toxicity, cediranib at this dose and schedule is not an effective treatment in patients with unresectable or metastatic HCC.