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Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab

The Pharmacogenomics Journal volume 12, pages 468–475 (2012)Cite this article

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Abstract

The aim of the study was to evaluate the association of vascular endothelial growth factor (VEGF) genotypes with treatment efficacy in a randomized trial. This study compared two chemotherapy regimens (FOLFIRI versus XELIRI) combined with bevacizumab, as first-line treatment for metastatic colorectal cancer. DNA was extracted from blood samples of 173 patients participating in the trial. Genotyping was performed for selected SNPs (VEGF−1154, +936, −634, −2578 and −1498). All candidate genotypes were evaluated for associations with overall survival (OS), progression-free survival (PFS) and response rate (RR). There were no significant differences with respect to the distribution of genotypes in the treatment groups. The VEGF−1154 GG genotype was more frequent in patients not responding to treatment compared with responders (65.5 versus 39.8%, P=0.032). Furthermore, the VEGF−1154 GG genotype was associated with inferior median OS compared with GA (hazards ratio=1.68; 95% confidence interval: 1.10–2.57; P=0.016) or with the alternative genotypes (GA and AA) combined (hazards ratio=1.62; 95% confidence interval: 1.09–2.40; P=0.017). In multivariate analysis, the VEGF−1154 GG genotype remained a significant adverse factor for OS. Our results support the potential predictive ability of VEGF genotypes in patients with metastatic colorectal cancer receiving irinotecan-based chemotherapy plus bevacizumab, in terms of RR and OS. However, current results should be validated prospectively, in larger cohorts.

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Acknowledgements

Funding source: The study was supported by a Hellenic Cooperative Oncology Group (HeCOG) research grant (HE TR_10).

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Authors and Affiliations

  1. Department of Medicine, Division of Oncology, University Hospital of Patras, Rion, Greece

    A K Koutras & H P Kalofonos

  2. Department of Medicine, Division of Oncology, Molecular Oncology Laboratory, University Hospital of Patras, Rion, Greece

    A G Antonacopoulou & F-I Dimitrakopoulos

  3. Biostatistics Section, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece

    A G Eleftheraki

  4. 2nd Propaedeutic Department of Internal Medicine, Oncology Section, University General Hospital ‘Attikon’, Athens, Greece

    A Koumarianou & D Pectasides

  5. Oncology Department, General Hospital of Chania, Crete, Greece

    I Varthalitis & I Bompolaki

  6. Molecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research ‘Demokritos’, Athens, Greece

    F Fostira

  7. 3rd Department of Medical Oncology, ‘Agii Anargiri’ Cancer Hospital, Athens, Greece

    J Sgouros

  8. Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece

    E Briasoulis

  9. Department of Clinical Therapeutics, ‘Alexandra’ Hospital, University of Athens School of Medicine, Athens, Greece

    E Bournakis

  10. 1st Department of Medical Oncology, ‘Metropolitan’ Hospital, Athens, Greece

    D Bafaloukos

  11. 2nd Department of Medical Oncology, ‘Metropolitan’ Hospital, Athens, Greece

    E Galani

  12. Translational Research Section, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece

    K T Kalogeras

  13. Department of Medical Oncology, ‘Papageorgiou’ Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

    K T Kalogeras & G Fountzilas

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  1. A K Koutras
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Correspondence to A K Koutras.

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Koutras, A., Antonacopoulou, A., Eleftheraki, A. et al. Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab. Pharmacogenomics J 12, 468–475 (2012). https://doi.org/10.1038/tpj.2011.37

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