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Int J Med Sci 2012; 9(10):833-837. doi:10.7150/ijms.4914

Research Paper

VEGF -634C/G Genotype is Predictive of Long-term Survival after Treatment with a Definitive 5-Fluorouracil/cisplatin-based Chemoradiotherapy in Japanese Patients with Esophageal Squamous Cell Carcinoma

Takao Tamura 1,2, Akiko Kuwahara2,3, Motohiro Yamamori2,3, Kohshi Nishiguchi 2,4, Tsutomu Nakamura2, Tatsuya Okuno 2, Ikuya Miki 2, Yuki Manabe5, Toshiyuki Sakaeda 2,5 ✉

1. Department of Medical Oncology, Nara Hospital, Kinki University Faculty of Medicine, Nara 630-0293, Japan.
2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
3. School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
4. Department of Clinical Pharmacy, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
5. Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.

Abstract

Background: Reports have been accumulating that genetic properties are predictive of clinical response after and/or toxicity during cancer chemotherapy, but little information is available concerning effects on long-term survival. In this study, 49 Japanese patients with esophageal squamous cell carcinoma (ESCC) were followed up for 5 years after treatment with a definitive 5-fluorouracil (5-FU)/cisplatin (CDDP)-based chemoradiotherapy (CRT), and the effects of genotypes of vascular endothelial growth factor (VEGF) were retrospectively revaluated in terms of prediction of long-term survival.

Methods: A course consisted of the continuous infusion of 5-FU at 400 mg/m2/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m2/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week interval. The VEGF genotypes -1498T/C, -1154G/A, -634C/G, -7C/T, 936C/T, and 1612G/A were evaluated.

Results: The complete response (CR) rate was 46.9% (23/49). The 5-year survival rate was 42.9 % (21/49). There were 7 patients with a CR, but survival of less than 5 years. They died from myocardial infarction (N=1), sudden cardiac death after suffering from heart failure (N=1), acute myeloid leukemia that developed from myelodysplastic syndromes (N=1), factors not specified (N=2), oropharynx cancer (N=1), and tongue cancer (N=1). VEGF -634C/G had no effect on clinical response, but long-term survival depended on the genotype (p=0.033, Fisher's; p=0.038, Cochran-Armitage; p=0.079, Log-rank). The genotype frequency of 7 patients with a CR, but survival of less than 5 years was different from that for the other 42 patients (p=0.032, Fisher's). None of the other 5 genotypes evaluated affected either clinical response or survival.

Conclusions: VEGF -634C/G is possibly predictive of long-term survival after treatment with a definitive 5-FU/CDDP-based CRT. Further clinical studies with a larger number of cases are needed to clarify the effects of this genotype.

Keywords: esophageal squamous cell carcinoma, chemoradiotherapy, late toxicity, prognosis, vascular endothelial growth factor.

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How to cite this article:
Tamura T, Kuwahara A, Yamamori M, Nishiguchi K, Nakamura T, Okuno T, Miki I, Manabe Y, Sakaeda T. VEGF -634C/G Genotype is Predictive of Long-term Survival after Treatment with a Definitive 5-Fluorouracil/cisplatin-based Chemoradiotherapy in Japanese Patients with Esophageal Squamous Cell Carcinoma. Int J Med Sci 2012; 9(10):833-837. doi:10.7150/ijms.4914. Available from http://www.medsci.org/v09p0833.htm