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.

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/m(2)/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m(2)/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.

• Authors: Takao Tamura, Akiko Kuwahara, Motohiro Yamamori, Kohshi Nishiguchi, Tsutomu Nakamura, Tatsuya Okuno, Ikuya Miki, Yuki Manabe, Toshiyuki Sakaeda
• Journal: International journal of medical sciences (Int J Med Sci) Vol. 9 Issue 10 Pg. 833-7 ( 2012) ISSN: 1449-1907 [Electronic] Australia
• PMID: 23155356 (Publication Type: Journal Article)

Chemical References

• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Cisplatin
• Fluorouracil

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Squamous Cell (drug therapy, genetics, pathology, radiotherapy)
• Cisplatin (administration & dosage)
• Combined Modality Therapy
• Esophageal Neoplasms (drug therapy, genetics, pathology, radiotherapy)
• Esophageal Squamous Cell Carcinoma
• Female
• Fluorouracil (administration & dosage)
• Genotype
• Humans
• Japan
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• Retrospective Studies
• Survival Rate
• Treatment Outcome
• Vascular Endothelial Growth Factor A (genetics)