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
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.
