Serum VEGF-A and CCL5 levels as candidate biomarkers for efficacy and toxicity of regorafenib in patients with metastatic colorectal cancer.
Serum VEGF-A and CCL5 levels as candidate biomarkers for efficacy and toxicity of regorafenib in patients with metastatic colorectal cancer.
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DOI：
10.18632/oncotarget.9187
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发表时间：
2016-06-07
期刊：
影响因子：
--
通讯作者：
Yamaguchi T
中科院分区：
文献类型：
--
作者：
Suenaga M;Mashima T;Kawata N;Wakatsuki T;Horiike Y;Matsusaka S;Dan S;Shinozaki E;Seimiya H;Mizunuma N;Yamaguchi K;Yamaguchi T
瑞戈非尼是一种口服多激酶抑制剂，用作转移性结直肠癌（mCRC）的挽救治疗。我们检测了接受瑞戈非尼治疗的mCRC患者血清细胞因子水平是否与临床结局相关。在治疗开始前、第21天和疾病进展前收集血清样品，并检查11种血管生成和炎性细胞因子血清水平。共62例入组患者中的54例患者有资格进行分析。基线时趋化因子配体5（CCL 5）水平≤临界值（59959 pg/ml）与相对肿瘤缩小（P = 0.021）、更好的无进展生存期（PFS）（P = 0.036）和总生存期（OS）（P = 0.019）相关。第21天血管内皮生长因子A（VEGF-A）水平降低与PFS改善显著相关（P = 0.021）。CCL 5水平≤临界值与任何级别的手足皮肤反应（HFSR）（P = 0.025）和血小板减少症（P = 0.013）相关。基线时低趋化因子配体2水平与2级≤ HFSR相关。基线时血管生成素-2和碱性成纤维细胞生长因子（bFGF）水平升高分别与3级≤总胆红素升高和转氨酶升高相关。基线时低bFGF水平与3级≤高血压相关。未观察到与重度事件相关。基线血清CCL 5水平和血清VEGF-A水平的降低可作为接受瑞戈非尼的mCRC患者生存或治疗特异性毒性的潜在预测标志物。
Regorafenib is an oral multi-kinase inhibitor used as salvage therapy for metastatic colorectal cancer (mCRC). We tested whether serum cytokine levels are associated with clinical outcome in the mCRC patients receiving regorafenib. Serum samples were collected before treatment start, day 21, and progressive disease, and eleven angiogenic and inflammatory cytokine serum levels were examined. Fifty-four patients of a total of 62 enrolled patients were eligible for the analyses. The chemokine ligand 5 (CCL5) levels ≤ cut-off value (59959 pg/ml) at baseline was associated with relative tumor shrinkage (P = 0.021), better progression-free survival (PFS) (P = 0.036) and overall survival (OS) (P = 0.019). Vascular endothelial growth factor A (VEGF-A) levels showing a decrease on day 21 were significantly associated with a better PFS (P = 0.021). CCL5 levels ≤ cut-off was associated with any grade hand-foot skin reaction (HFSR) (P = 0.025) and thrombocytopenia (P = 0.013). Low chemokine ligand 2 levels at baseline were associated with grade 2 ≤ HFSR. High angiopoietin-2 and basic fibroblast growth factor (bFGF) levels at baseline were associated with grade 3 ≤ total bilirubin increase and transaminases increase, respectively. Low bFGF levels at baseline were associated with grade 3 ≤ hypertension. No correlation with severe events was observed. Baseline serum CCL5 levels and decrease of the serum VEGF-A levels may serve as potential predictive markers for survival or treatment-specific toxicities in mCRC patients receiving regorafenib.
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