Predictive value of VEGF gene polymorphisms for metastatic colorectal cancer patients receiving first-line treatment including fluorouracil, irinotecan, and bevacizumab
Predictive value of VEGF gene polymorphisms for metastatic colorectal cancer patients receiving first-line treatment including fluorouracil, irinotecan, and bevacizumab
复制标题
DOI：
10.1007/s00384-010-1108-1
复制
发表时间：
2011-02-01
影响因子：
2.8
通讯作者：
Roselli, Mario
中科院分区：
文献类型：
--
作者：
Formica, Vincenzo;Palmirotta, Raffaele;Roselli, Mario
为探讨生殖系血管内皮生长因子（VEGF）基因多态性（VGPs）对抗VEGF抗体贝伐单抗（Bev）治疗转移性结直肠癌（MCRC）疗效的影响，选择40例符合一线治疗条件的MCRC患者，采用FOLFIRI + Bev方案治疗，观察VGPs基因多态性对Bevacizumab疗效的影响。（男性/女性= 22：18，年龄（中位数）= 61岁）。在患者血液样品中评估启动子/5 'UTR区域内的八个VGP。主要终点是VGP与中位无进展生存期（mPFS）之间的相关性。VGP-2578、-1512、-1451、-1411和-460处于完全连锁不平衡，因此作为单倍型进行分析（两种变体：Haplo 1：A-18 bp插入-T-4G-C和Haplo 2：C-18 bp缺失-C-5G-T）。与23例Haplo 1/Haplo 1或Haplo 1/Haplo 2患者相比，17例Haplo 2/Haplo 2患者的mPFS显著更短（mPFS分别为9个月和15.4个月，p = 0.02;风险比（HR）为2.64）。此外，VGP-152（G/G vs. G/A + A/A）和-1154（G/G vs. G/A + A/A）与PFS显著相关（mPFS，8.9 vs. 15.4个月，p = 0.007; HR，3.53和9.8 vs. 16个月，p = 0.03，HR，2.32）。在包括已知影响预后的生化变量的多变量分析中，VGP-1154保留了mPFS的独立预测值（G/G相对于G/A + A/A = HR，4.43; p = 0.02）。关于ORR，仅VGP-634与缓解显著相关（G/G vs. G/C + C/C = 64% vs. 14%，p = 0.03）。研究的VGPs对OS和毒性没有显著影响，尽管这些数据需要在更大规模的试验中得到证实，但生殖系VGPs的研究可能有助于识别对抗VEGF药物更敏感的患者。
The aim of this study is to evaluate the influence of germline vascular endothelial growth factor (VEGF) gene polymorphisms (VGPs) on the efficacy of the anti-VEGF antibody bevacizumab (Bev) in metastatic colorectal cancer (MCRC) patients.Forty MCRC patients eligible for a first-line therapy were enrolled in this prospective trial and treated with FOLinate/Fluorouracil/Irinotecan (FOLFIRI) + Bev (male/female = 22:18, age (median) = 61 years). Eight VGPs within the promoter/5'UTR region were evaluated in patient blood samples. Primary endpoint was association between VGPs and median progression-free survival (mPFS). Overall radiological response rate (ORR), overall survival (OS), and toxicity were assessed as secondary outcomes.VGPs -2578, -1512, -1451, -1411, and -460 were in complete linkage disequilibrium and therefore analyzed as haplotype (two variants: Haplo1: A-18 bp insertion-T-4G-C and Haplo2: C-18 bp deletion-C-5G-T, respectively). Seventeen patients Haplo2/Haplo2 had significantly shorter mPFS compared to 23 patients Haplo1/Haplo1 or Haplo1/Haplo2 (mPFS, 9 vs. 15.4 months, respectively, p = 0.02; hazard ratio (HR), 2.64). Also, VGPs -152 (G/G vs. G/A + A/A) and -1154 (G/G vs. G/A + A/A) were significantly associated with PFS (mPFS, 8.9 vs. 15.4 months, p = 0.007; HR, 3.53 and 9.8 vs. 16 months, p = 0.03, HR, 2.32, respectively). In the multivariate analysis including also biochemical variables known to influence prognosis, VGP -1154 retained an independent predictive value for mPFS (G/G over G/A + A/A = HR, 4.43; p = 0.02). With regard to ORR, only VGP -634 was significantly associated with response (G/G vs. G/C + C/C = 64% vs. 14%, p = 0.03). No significant influence on OS and toxicity by the investigated VGPs was observed.Although these data need to be confirmed in larger trials, investigation of germline VGPs may help identify patients who are more sensitive to anti-VEGF agents.