title: 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.affiliation: Department of Medical Oncology, Nara Hospital, Kinki University Faculty of Medicine, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Tamura
authors.forename: Akiko
authors.initials: A
authors.lastname: Kuwahara
authors.forename: Motohiro
authors.initials: M
authors.lastname: Yamamori
authors.forename: Kohshi
authors.initials: K
authors.lastname: Nishiguchi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Okuno
authors.forename: Ikuya
authors.initials: I
authors.lastname: Miki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Manabe
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakaeda
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D002945:Cisplatin; D005472:Fluorouracil