Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer
Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer
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DOI：
10.1038/bjc.2011.85
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发表时间：
2011-04-12
影响因子：
8.8
通讯作者：
Bocci, G.
中科院分区：
文献类型：
--
作者：
Loupakis, F.;Cremolini, C.;Bocci, G.
背景：鉴定分子和遗传标记来预测或监测贝伐单抗（BV）的疗效是转移性结直肠癌（mCRC）治疗的关键问题。方法：采用酶联免疫吸附试验（ELISA）测定25例参加GONO-FOLFOXIRI联合BV作为mCRC一线治疗的患者在不同时间点的血浆血管内皮生长因子（VEGF）、胎盘生长因子（PlGF）、可溶性VEGF受体2 （sVEGFR-2）和血小板反应蛋白-1 （TSP-1）水平。VEGF: -2578A/C、-1498C/T、-1154A/G、-634C/G、936C/T；和VEGFR-2: -604A/G， +1192C/T和+1719A/T，共在54例患者中评估多态性。结果：GONO-FOLFOXIRI联合BV治疗可长期显著降低血浆游离、生物活性VEGF浓度。有趣的是，在PD时，VEGF浓度仍然低于基线。相反，与基线相比，治疗期间PlGF水平升高，表明可能在肿瘤耐药中起作用；PD时sVEGFR-2升高，TSP-1升高。未发现评估的多态性与结果的关联。结论：我们的研究提示了进展性疾病患者对联合治疗耐药的可能机制，将在正在进行的III期随机研究中进行测试。英国癌症杂志（2011）104,1262-1269。doi:10.1038/bjc.2011.85 www.bjcancer.com 2011年3月15日在线发表(C) 2011 Cancer Research UK
BACKGROUND: The identification of molecular and genetic markers to predict or monitor the efficacy of bevacizumab (BV) represents a key issue in the treatment of metastatic colorectal cancer (mCRC).METHODS: Plasma levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble VEGF receptor 2 (sVEGFR-2) and thrombospondin-1 (TSP-1) were assessed by ELISA assay at different time points in a cohort of 25 patients enroled in a phase II trial of GONO-FOLFOXIRI plus BV as first-line treatment of mCRC. VEGF: -2578A/C, -1498C/T, -1154A/G, -634C/G and 936C/T; and VEGFR-2: -604A/G, +1192C/T and +1719A/T, polymorphisms were assessed in a total of 54 patients.RESULTS: Treatment with GONO-FOLFOXIRI plus BV determined a prolonged and significant reduction in plasma free, biologically active VEGF concentration. Interestingly, VEGF concentrations remained lower than at baseline also at the time of PD. Conversely, PlGF levels increased during the treatment if compared with baseline, suggesting a possible role in tumour resistance; moreover, sVEGFR-2 increased at the time of PD, as well as TSP-1. No association of assessed polymorphisms with outcome was found.CONCLUSION: Our study suggested the possible mechanisms of resistance to combined therapy in those patients with a progressive disease to be tested in ongoing phase III randomised studies. British Journal of Cancer (2011) 104, 1262-1269. doi:10.1038/bjc.2011.85 www.bjcancer.com Published online 15 March 2011 (C) 2011 Cancer Research UK