Suenaga Mitsukuni, Mashima Tetsuo, Kawata Naomi, Wakatsuki Takeru, Horiike Yuki, Matsusaka Satoshi, Dan Shingo, Shinozaki Eiji, Seimiya Hiroyuki, Mizunuma Nobuyuki, Yamaguchi Kensei, Yamaguchi Toshiharu
Department of Gastroenterological and Chemotherapy Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
Oncotarget. 2016 Jun 7;7(23):34811-23. doi: 10.18632/oncotarget.9187.
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.
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。我们测试了血清细胞因子水平是否与接受瑞戈非尼治疗的mCRC患者的临床结局相关。在治疗开始前、第21天和疾病进展时收集血清样本，并检测11种血管生成和炎性细胞因子的血清水平。共有62名入组患者中的54名符合分析条件。基线时趋化因子配体5（CCL5）水平≤临界值（59959 pg/ml）与肿瘤相对缩小相关（P = 0.021）、无进展生存期（PFS）更好（P = 0.036）和总生存期（OS）更长（P = 0.019）。第21天时血管内皮生长因子A（VEGF-A）水平下降与更好的PFS显著相关（P = 0.021）。CCL5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。基线时趋化因子配体2水平低与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）水平高分别与3级≤总胆红素升高和转氨酶升高相关。基线时bFGF水平低与3级≤高血压相关。未观察到与严重事件的相关性。基线血清CCL5水平和血清VEGF-A水平的下降可能作为接受瑞戈非尼治疗的mCRC患者生存或治疗特异性毒性的潜在预测标志物。
