Association between bevacizumab-related hypertension and vascular endothelial growth factor (VEGF) gene polymorphisms in
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ORIGINAL ARTICLE
Association between bevacizumab-related hypertension and vascular endothelial growth factor (VEGF) gene polymorphisms in Japanese patients with metastatic colorectal cancer Sachi Morita • Keisuke Uehara • Goro Nakayama • Takashi Shibata • Tomoyo Oguri • Megumi Inada-Inoue • Tomoya Shimokata • Mihoko Sugishita Ayako Mitsuma • Yuichi Ando
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Received: 25 July 2012 / Accepted: 5 November 2012 / Published online: 17 November 2012 Ó Springer-Verlag Berlin Heidelberg 2012
Abstract Purpose Bevacizumab, a monoclonal antibody that binds to VEGF, has a well-known toxic effect of hypertension. We studied possible associations between bevacizumabrelated 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 Bevacizumab Hypertension VEGF SNPs Colorectal cancer
Introduction S. Morita (&) T. Shibata M. Inada-Inoue T. Shimokata M. Sugishita A. Mitsuma Y. Ando Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8560, Japan e-mail: [email protected] K. Uehara Division of Surgical Oncology, Department of Surgery, Nagoya Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, Japan G. Nakayama Department of Gastroenterological Surgery, Nagoya Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, Japan T. Oguri Department of Respiratory Medicine, Nagoya Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, Japan
Bevacizumab is a recombinant humanized monoclonal antibody that binds to vascular endothelial growth factor (VEGF) and prevents it from binding to VEGF receptor (VEGFR). It is widely used for combination chemotherapy in patients with metastatic solid tumors and has a well-known toxic effect of hypertension. One of the effects caused by VEGF binding to VEGFR is
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