Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 2, pp 405–411

Association between bevacizumab-related hypertension and vascular endothelial growth factor (VEGF) gene polymorphisms in Japanese patients with metastatic colorectal cancer

Authors

    • Department of Clinical Oncology and ChemotherapyNagoya University Hospital
  • Keisuke Uehara
    • Division of Surgical Oncology, Department of SurgeryNagoya Graduate School of Medicine
  • Goro Nakayama
    • Department of Gastroenterological SurgeryNagoya Graduate School of Medicine
  • Takashi Shibata
    • Department of Clinical Oncology and ChemotherapyNagoya University Hospital
  • Tomoyo Oguri
    • Department of Respiratory MedicineNagoya Graduate School of Medicine
  • Megumi Inada-Inoue
    • Department of Clinical Oncology and ChemotherapyNagoya University Hospital
  • Tomoya Shimokata
    • Department of Clinical Oncology and ChemotherapyNagoya University Hospital
  • Mihoko Sugishita
    • Department of Clinical Oncology and ChemotherapyNagoya University Hospital
  • Ayako Mitsuma
    • Department of Clinical Oncology and ChemotherapyNagoya University Hospital
  • Yuichi Ando
    • Department of Clinical Oncology and ChemotherapyNagoya University Hospital
Original Article

DOI: 10.1007/s00280-012-2028-2

Cite this article as:
Morita, S., Uehara, K., Nakayama, G. et al. Cancer Chemother Pharmacol (2013) 71: 405. doi:10.1007/s00280-012-2028-2

Abstract

Purpose

Bevacizumab, a monoclonal antibody that binds to VEGF, has a well-known toxic effect of hypertension. We studied possible associations between bevacizumab-related hypertension and gene polymorphisms to assure safer cancer therapy.

Methods

We retrospectively studied 60 Japanese patients with metastatic colorectal cancer who had received bevacizumab-based chemotherapy. Genotypes were determined for five well-known functional single-nucleotide polymorphism of the VEGF gene at positions C-2578A, T-1498C, G-1154A, G-634C, and C936T. Hypertension was graded according to CTCAE v4.0 on the basis of home blood pressure.

Results

The VEGF-2578 C/C and -1498 T/T genotypes were associated with significantly less hypertension during the first 2 months of bevacizumab-based chemotherapy (p = 0.004, p = 0.025, respectively). During the treatment period as a whole, the VEGF-2578 C/C and 936 C/C genotypes were associated with less hypertension (p = 0.031, p = 0.043, respectively). Preexisting hypertension was not associated with bevacizumab-related hypertension.

Conclusions

This study demonstrated a significant relation between a lower incidence of grade 2 or higher bevacizumab-related hypertension and the VEGF-2578 C/C genotype for the entire treatment period in Japanese patients with metastatic colorectal cancer. This genotype might be useful for ensuring safer treatment of patients who receive bevacizumab-based chemotherapy.

Keywords

BevacizumabHypertensionVEGFSNPsColorectal cancer

Copyright information

© Springer-Verlag Berlin Heidelberg 2012