Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma
Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma
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DOI：
10.1200/jco.2007.15.9947
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发表时间：
2008-06-20
影响因子：
45.3
通讯作者：
Schwartz, Jonathan D.
中科院分区：
文献类型：
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作者：
Siegel, Abby B.;Cohen, Emil I.;Schwartz, Jonathan D.
PurposeTo确定贝伐单抗，抗血管内皮生长因子（VEGF）的单克隆抗体，在不可切除的肝细胞癌（HCC）的临床和生物学效果，患者和MethodsAdults与器官局限性HCC，东部肿瘤协作组性能状态0至2，和代偿性肝病是合格的。患者接受贝伐珠单抗5 mg/ kg（n = 12）或10 mg/ kg（n = 34），每2周一次，直至疾病进展或治疗限制性毒性。主要目的是确定贝伐单抗是否将6个月无进展生存期（PFS）率从40%提高到60%。次要终点包括确定贝伐单抗对动脉增强和血浆细胞因子水平和患者血浆的能力，以支持血管生成通过在体外assay.ResultsThe研究包括46例患者，其中6人有客观的反应（13%; 95%CI，3%至23%），和65%的无进展6个月。中位PFS时间为6.9个月（95% CI，6.5 - 9.1个月）; 1年总生存率为53%，2年为28%，3年为23%。3 - 4级不良事件包括高血压（15%）和血栓形成（6%，包括4%的动脉血栓形成）。11%的患者发生3级或以上出血，包括1例致死性静脉曲张出血。贝伐单抗与动态对比增强磁共振成像肿瘤增强显著降低以及循环VEGF-A和基质衍生因子-1水平降低相关。功能性血管生成活性与VEGF-A水平在patient plasma.ConclusionWe观察到显着的临床和生物活性贝伐单抗在非转移性肝癌，并实现了主要的研究终点。11%的患者发生严重出血并发症。在精心挑选的患者中进行进一步评估是必要的。
PurposeTo determine the clinical and biologic effects of bevacizumab, an anti -vascular endothelial growth factor (VEGF) monoclonal antibody, in unresectable hepatocellular carcinoma (HCC).Patients and MethodsAdults with organ-confined HCC, Eastern Cooperative Oncology Group performance status of 0 to 2, and compensated liver disease were eligible. Patients received bevacizumab 5 mg/ kg (n = 12) or 10 mg/ kg (n = 34) every 2 weeks until disease progression or treatment-limiting toxicity. The primary objective was to determine whether bevacizumab improved the 6-month progression-free survival (PFS) rate from 40% to 60%. Secondary end points included determining the effects of bevacizumab on arterial enhancement and on plasma cytokine levels and the capacity of patients' plasma to support angiogenesis via an in vitro assay.ResultsThe study included 46 patients, of whom six had objective responses (13%; 95% CI, 3% to 23%), and 65% were progression free at 6 months. Median PFS time was 6.9 months (95% CI, 6.5 to 9.1 months); overall survival rate was 53% at 1 year, 28% at 2 years, and 23% at 3 years. Grade 3 to 4 adverse events included hypertension (15%) and thrombosis (6%, including 4% with arterial thrombosis). Grade 3 or higher hemorrhage occurred in 11% of patients, including one fatal variceal bleed. Bevacizumab was associated with significant reductions in tumor enhancement by dynamic contrast-enhanced magnetic resonance imaging and reductions in circulating VEGF-A and stromal-derived factor-1 levels. Functional angiogenic activity was associated with VEGF-A levels in patient plasma.ConclusionWe observed significant clinical and biologic activity for bevacizumab in nonmetastatic HCC and achieved the primary study end point. Serious bleeding complications occurred in 11% of patients. Further evaluation is warranted in carefully selected patients.