Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma: an open-label, multicentre, phase II study
Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma: an open-label, multicentre, phase II study
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DOI：
10.1016/s1470-2045(09)70171-8
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发表时间：
2009-08-01
期刊：
影响因子：
51.1
通讯作者：
Cheng, Ann Lii
中科院分区：
文献类型：
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作者：
Faivre, Sandrine;Raymond, Eric;Cheng, Ann Lii
背景肝细胞癌的肿瘤扩散在一定程度上依赖于新生血管的生成。在这项在欧洲和亚洲进行的开放、多中心的II期试验中，评价了具有抗血管生成特性的多靶点酪氨酸激酶抑制剂舒尼替尼在晚期不可切除肝癌患者中的应用。方法2006年2月至7月，符合条件的患者接受重复口服舒尼替尼(50 mg/d，4周，然后停药2周)。这项SIMON两阶段II试验的主要终点是根据实体肿瘤反应评估标准(RECIST)标准的客观应答率，预期应答率为15%。这项试验在ClinicalTrials.gov注册，编号NCT00247676。在37名入选的患者中，1名(2.7%)患者出现确认的部分应答，总体客观应答率为2.7%(95%可信区间0.1-14.2)；在此基础上，试验没有进行到第二阶段。37例患者中13例(35%)病情稳定3个月以上。常见的3级和4级不良反应包括血小板减少(14/37，37.8%)、中性粒细胞减少(9/37，24.3%)、乏力(5/37，13.5%)、手足综合征(4/37，10.8%)和贫血(4/37，10.8%)。在37例患者中，有4例(10.8%)的死亡可能与治疗有关。在不能切除的肝癌患者中，解释苏尼替尼每天50 mg的剂量显示出明显的毒性。应答率很低，研究没有达到基于RECIST标准的主要终点。
Background Hepatocellular carcinoma (HCC) tumour spread is partly dependent on neoangiogenesis. In this open-label, multicentre, phase II trial done in Europe and Asia, sunitinib, a multitargeted tyrosine-kinase inhibitor with anti-angiogenic properties, was assessed in patients with advanced unresectable HCC.Methods Between February and July, 2006, eligible patients were enrolled and treated with repeated cycles of oral sunitinib (50 mg/day for 4 weeks, followed by 2 weeks off treatment). The primary endpoint of this Simon two-stage phase II trial was objective response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria, with an expected response rate of 15%. This trial is registered with ClinicalTrials.gov, number NCT00247676.Findings Of 37 patients enrolled, one (2.7%) patient experienced a confirmed partial response, giving an overall objective response rate of 2.7% (95% CI 0.1-14.2); on the basis of this, the trial did not proceed to the second stage. 13 (35%) of 37 patients achieved stable disease for over 3 months. Commonly observed grade 3 and 4 adverse events included thrombocytopenia (14 of 37; 37.8%), neutropenia (nine of 37; 24.3%), asthenia (five of 37; 13.5%), hand-foot syndrome (four of 37; 10.8%), and anaemia (four of 37; 10.8%). There were four deaths among the 37 patients (10.8%) that were possibly related to treatment.Interpretation Sunitinib showed pronounced toxicities at a dose of 50 mg/day in patients with unresectable HCC. The response rate was low, and the study did not meet the primary endpoint based on RECIST criteria.Funding Pfizer Oncology.