使用血清血管生成标志物预测肝癌患者索拉非尼的治疗效果。
Predicting the treatment effect of sorafenib using serum angiogenesis markers in patients with hepatocellular carcinoma.
机构信息
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
出版信息
J Gastroenterol Hepatol. 2011 Nov;26(11):1604-11. doi: 10.1111/j.1440-1746.2011.06887.x.
BACKGROUND AND AIM
Sorafenib, the first agent demonstrated to have efficacy to improve the survival of patients with advanced hepatocellular carcinoma (HCC), is an active multikinase inhibitor affecting angiogenesis and tumor proliferation. We analyzed cytokines related to angiogenesis or cell proliferation, and tried to determine their utility as biomarkers of sorafenib treatment effect for HCC.
METHODS
Nine serum cytokines (angiopoietin-2 [Ang-2], follistatin, granulocyte colony-stimulating factor [G-CSF], hepatocyte growth factor [HGF], interleukin-8 [IL-8], leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor) were measured in 30 HCC patients treated with sorafenib, and the effects of treatment were compared using modified Response Evaluation Criteria in Solid Tumors.
RESULTS
All but IL-8 were significantly higher at baseline in patients with progressive disease. Progression-free survival was significantly shorter in patients with high levels of Ang-2, G-CSF, HGF, and leptin, and the hazard ratios were 2.51, 6.89, 2.55, and 4.14, respectively. As the number of cytokines at a high level increased, the treatment response deteriorated. Disease progression was seen in three of 12 (25.0%) patients with zero to two high biomarkers, two of six (33.3%) patients with 3-5 high biomarkers, and 10 of 12 (83.3%) patients with six to eight high biomarkers (P=0.008). The prognosis of all patients with eight high biomarkers was progressive disease.
CONCLUSION
High levels of serum cytokines at baseline were correlated with poor effects of sorafenib treatment in patients with HCC.
背景与目的
索拉非尼是首个被证明能改善晚期肝细胞癌（HCC）患者生存的药物，它是一种有效的多激酶抑制剂，可影响血管生成和肿瘤增殖。我们分析了与血管生成或细胞增殖相关的细胞因子，并试图确定它们作为索拉非尼治疗 HCC 效果的生物标志物的效用。
方法
在 30 名接受索拉非尼治疗的 HCC 患者中测量了 9 种血清细胞因子（血管生成素-2 [Ang-2]、卵泡抑素、粒细胞集落刺激因子 [G-CSF]、肝细胞生长因子 [HGF]、白细胞介素-8 [IL-8]、瘦素、血小板衍生生长因子-BB、血小板内皮细胞黏附分子-1 和血管内皮生长因子），并使用改良的实体瘤反应评价标准比较了治疗效果。
结果
在进展性疾病患者中，除 IL-8 外，所有细胞因子在基线时均显著升高。在 Ang-2、G-CSF、HGF 和瘦素水平较高的患者中，无进展生存期明显较短，风险比分别为 2.51、6.89、2.55 和 4.14。随着高水平细胞因子数量的增加，治疗反应恶化。在零至两个高生物标志物的 12 名患者中，有 3 名（25.0%）出现疾病进展，在 3-5 个高生物标志物的 6 名患者中，有 2 名（33.3%）出现疾病进展，在 6-8 个高生物标志物的 12 名患者中，有 10 名（83.3%）出现疾病进展（P=0.008）。所有 8 个高生物标志物患者的预后均为疾病进展。
结论
基线时血清细胞因子水平较高与 HCC 患者索拉非尼治疗效果不佳相关。
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