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Dose escalating study of cetuximab and 5-FU/folinic acid (FA)/oxaliplatin/irinotecan (FOLFOXIRI) in first line therapy of patients with metastatic colorectal cancer.西妥昔单抗与5-氟尿嘧啶/亚叶酸（FA）/奥沙利铂/伊立替康（FOLFOXIRI）用于转移性结直肠癌患者一线治疗的剂量递增研究。
BMC Cancer. 2014 Jul 19;14:521. doi: 10.1186/1471-2407-14-521.
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Prognostic advantage of irinotecan dose escalation according to uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping in patients with metastatic colorectal cancer treated with bevacizumab combined with 5-fluorouracil/leucovorin with irinotecan in a first-line setting.贝伐珠单抗联合氟尿嘧啶/亚叶酸钙和伊立替康一线治疗转移性结直肠癌患者中，根据尿苷二磷酸葡萄糖醛酸基转移酶 1A1（UGT1A1）基因分型进行伊立替康剂量升级的预后优势。
Transl Res. 2014 Aug;164(2):169-76. doi: 10.1016/j.trsl.2013.12.009. Epub 2014 Jan 4.
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Current approaches and challenges for monitoring treatment response in colon and rectal cancer.监测结肠癌和直肠癌治疗反应的当前方法与挑战
J Cancer. 2014 Jan 1;5(1):31-43. doi: 10.7150/jca.7987.
4
Gene expression profiling identifies EPHB4 as a potential predictive biomarker in colorectal cancer patients treated with bevacizumab.基因表达谱分析鉴定 EphB4 为贝伐珠单抗治疗的结直肠癌患者的潜在预测性生物标志物。
Med Oncol. 2013;30(2):572. doi: 10.1007/s12032-013-0572-1. Epub 2013 Apr 12.
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Molecular markers to predict outcome to antiangiogenic therapies in colorectal cancer: current evidence and future perspectives.预测结直肠癌抗血管生成治疗结局的分子标志物：当前证据和未来展望。
Cancer Treat Rev. 2013 Dec;39(8):908-24. doi: 10.1016/j.ctrv.2013.02.004. Epub 2013 Mar 16.
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Analysis of PTEN, VEGF, HER2 and P53 status in determining colorectal cancer benefit from bevacizumab therapy.分析PTEN、VEGF、HER2和P53状态以确定结直肠癌患者从贝伐单抗治疗中获益的情况。
Asian Pac J Cancer Prev. 2012;13(12):6397-401. doi: 10.7314/apjcp.2012.13.12.6397.
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Magnetic resonance imaging of rectal cancer.直肠癌的磁共振成像
Radiol Clin North Am. 2013 Jan;51(1):121-31. doi: 10.1016/j.rcl.2012.09.012.
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Association between VEGF splice isoforms and progression-free survival in metastatic colorectal cancer patients treated with bevacizumab.血管内皮生长因子剪接异构体与贝伐单抗治疗转移性结直肠癌患者无进展生存期的关系。
Clin Cancer Res. 2012 Nov 15;18(22):6384-91. doi: 10.1158/1078-0432.CCR-12-2223. Epub 2012 Oct 25.
9
Predictive value of vascular endothelial growth factor overexpression in early relapse of colorectal cancer patients after curative resection.血管内皮生长因子过表达对结直肠癌患者根治性切除术后早期复发的预测价值。
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10
Circulating vascular endothelial growth factor receptor 2/pAkt-positive cells as a functional pharmacodynamic marker in metastatic colorectal cancers treated with antiangiogenic agent.循环血管内皮生长因子受体 2/pAkt 阳性细胞作为抗血管生成剂治疗转移性结直肠癌的功能药效标志物。
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治疗期间VEGF表达降低可能是转移性结直肠癌患者对一线FOLFIRI联合贝伐单抗治疗反应性的一个预测指标。

Decreased peritherapeutic VEGF expression could be a predictor of responsiveness to first-line FOLFIRI plus bevacizumab in mCRC patients.

作者信息

Tsai Hsiang-Lin, Lin Chih-Hung, Huang Ching-Wen, Yang I-Ping, Yeh Yung-Sung, Hsu Wen-Hung, Wu Jeng-Yih, Kuo Chao-Hung, Tseng Fan-Ying, Wang Jaw-Yuan

机构信息

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan ; Division of General Surgery Medicine, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan ; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan ; Program of Bachelor of Health Beauty, School of Medical and Health Sciences, Fooyin University Kaohsiung, Taiwan ; Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University Kaohsiung, Taiwan ; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan.

Deaprtment of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung, Taiwan.

出版信息

Int J Clin Exp Pathol. 2015 Feb 1;8(2):1900-10. eCollection 2015.

PMID:25973082
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4396259/
Abstract

OBJECTIVE

Bevacizumab is the only anti-angiogenic agent approved in first-line therapy for metastatic colorectal cancer (mCRC). Although chemotherapy plus bevacizumab has led to improve outcomes for mCRC patients and is a common choice for first-line treatment of mCRC, previous research has established no prominent biomarker that can help to select patients who may benefit from bevacizumab in order to improve cost-effectiveness and therapeutic outcomes. The aim of this study was to compare pre- and post-therapeutic VEGF immunohistochemical (IHC) expression in mCRC patients treated with FOLFIRI plus bevacizumab to identify its potential role as a predictive biomarker.

METHODS

A total of 57 mCRC patients who underwent FOLFIRI combined with bevacizumab chemotherapy as a first-line neoadjuvant regimen were enrolled and clinical outcome data analyzed.

RESULTS

Low post-therapeutic VEGF expression (P < 0.001) and decreased peri-therapeutic VEGF expression (P < 0.001) were significantly predictive factors of responders. Furthermore, the 6-month progression-free survival (PFS) rate in mCRC patients with decreased peri-therapeutic VEGF expression was significantly better than the rate for those patients with no peri-therapeutic VEGF expression alterations (P = 0.033).

CONCLUSIONS

Decreased peri-therapeutic VEGF expression in mCRC patients could probably be used to predict responsiveness to bevacizumab and subsequent PFS in clinical practice.

摘要

目的

贝伐单抗是唯一被批准用于转移性结直肠癌（mCRC）一线治疗的抗血管生成药物。尽管化疗联合贝伐单抗已改善了mCRC患者的预后，且是mCRC一线治疗的常用选择，但既往研究尚未确立可帮助选择可能从贝伐单抗治疗中获益的患者的显著生物标志物，以提高成本效益和治疗效果。本研究旨在比较接受FOLFIRI联合贝伐单抗治疗的mCRC患者治疗前后的VEGF免疫组化（IHC）表达，以确定其作为预测生物标志物的潜在作用。

方法

共纳入57例接受FOLFIRI联合贝伐单抗化疗作为一线新辅助方案的mCRC患者，并分析临床结局数据。

结果

治疗后VEGF低表达（P<0.001）和治疗期间VEGF表达降低（P<0.001）是反应者的显著预测因素。此外，治疗期间VEGF表达降低的mCRC患者的6个月无进展生存期（PFS）率显著优于治疗期间VEGF表达无改变的患者（P=0.033）。

结论

mCRC患者治疗期间VEGF表达降低可能可用于在临床实践中预测对贝伐单抗的反应及随后的PFS。