Pharmacogenetic Angiogenesis Profiling for First-line Bevacizumab plus Oxaliplatin-Based Chemotherapy in Patients with Metastatic Colorectal Cancer
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- Armin Gerger
- Authors' Affiliations: 1Division of Medical Oncology, 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, and 3USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California; and 4Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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- Anthony El-Khoueiry
- Authors' Affiliations: 1Division of Medical Oncology, 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, and 3USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California; and 4Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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- Wu Zhang
- Authors' Affiliations: 1Division of Medical Oncology, 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, and 3USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California; and 4Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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- Dongyun Yang
- Authors' Affiliations: 1Division of Medical Oncology, 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, and 3USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California; and 4Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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- Harpreet Singh
- Authors' Affiliations: 1Division of Medical Oncology, 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, and 3USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California; and 4Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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- Pierre Bohanes
- Authors' Affiliations: 1Division of Medical Oncology, 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, and 3USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California; and 4Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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- Yan Ning
- Authors' Affiliations: 1Division of Medical Oncology, 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, and 3USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California; and 4Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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- Thomas Winder
- Authors' Affiliations: 1Division of Medical Oncology, 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, and 3USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California; and 4Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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- Melissa J. LaBonte
- Authors' Affiliations: 1Division of Medical Oncology, 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, and 3USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California; and 4Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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- Peter M. Wilson
- Authors' Affiliations: 1Division of Medical Oncology, 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, and 3USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California; and 4Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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- Leonor Benhaim
- Authors' Affiliations: 1Division of Medical Oncology, 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, and 3USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California; and 4Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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- David Paez
- Authors' Affiliations: 1Division of Medical Oncology, 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, and 3USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California; and 4Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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- Rita El-Khoueiry
- Authors' Affiliations: 1Division of Medical Oncology, 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, and 3USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California; and 4Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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- Gudrun Absenger
- Authors' Affiliations: 1Division of Medical Oncology, 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, and 3USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California; and 4Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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- Heinz-Josef Lenz
- Authors' Affiliations: 1Division of Medical Oncology, 2Department of Preventive Medicine, Norris Comprehensive Cancer Center, and 3USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California; and 4Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
抄録
<jats:title>Abstract</jats:title> <jats:p>Purpose: There is substantial germline genetic variability within angiogenesis pathway genes, thereby causing interindividual differences in angiogenic capacity and resistance to antiangiogenesis therapy. We investigated germline polymorphisms in genes involved in VEGF-dependent and -independent angiogenesis pathways to predict clinical outcome and tumor response in metastatic colorectal cancer (mCRC) patients treated with bevacizumab and oxaliplatin-based chemotherapy.</jats:p> <jats:p>Experimental Design: A total of 132 patients treated with first-line bevacizumab and FOLFOX or XELOX were included in this study. Genomic DNA was isolated from whole-blood samples by PCR-RFLP or direct DNA sequencing. The endpoints of the study were progression-free survival (PFS), overall survival (OS), and response rate (RR).</jats:p> <jats:p>Results: The minor alleles of EGF rs444903 A>G and IGF-1 rs6220 A>G were associated with increased OS and remained significant in multivariate Cox regression analysis (HR: 0.52; 95% CI: 0.31–0.87; adjusted P = 0.012 and HR: 0.60; 95% CI: 0.36–0.99; adjusted P = 0.046, respectively). The minor allele of HIF1α rs11549465 C>T was significantly associated with increased PFS but lost its significance in multivariate analysis. CXCR1 rs2234671 G>C, CXCR2 rs2230054 T>C, EGFR rs2227983 G>A, and VEGFR-2 rs2305948 C>T predicted tumor response, with CXCR1 rs2234671 G>C remaining significant in multiple testing (Pact = 0.003).</jats:p> <jats:p>Conclusion: In this study, we identified common germline variants in VEGF-dependent and -independent angiogenesis genes predicting clinical outcome and tumor response in patients with mCRC receiving first-line bevacizumab and oxaliplatin-based chemotherapy. Clin Cancer Res; 17(17); 5783–92. ©2011 AACR.</jats:p>
収録刊行物
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- Clinical Cancer Research
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Clinical Cancer Research 17 (17), 5783-5792, 2011-09-01
American Association for Cancer Research (AACR)