title: Prognostic significance of serum levels of vascular endothelial growth factor and insulin-like growth factor-1 in advanced gastric cancer patients treated with FOLFOX chemotherapy.
abstract: BACKGROUND
  Tumor vascular endothelial growth factor (VEGF) is a key angiogenic factor and may have an impact on tumor progression and response to chemotherapy. The insulin-like growth factor (IGF) system is related to cell proliferation and tumor growth. However, there is limited available data regarding the clinical and prognostic significance of VEGF or IGF-1 in advanced gastric cancer. The aim of this study was to evaluate the prognostic significance of serum VEGF and IGF-1 levels in advanced gastric cancer patients who were treated with oxaliplatin/5-fluorouracil (FOLFOX).
  
  
  METHODS
  The study population consisted of 100 advanced gastric cancer patients (median age 56 years). Patients were treated with oxaliplatin 85 mg/m(2) as a 2-hour infusion on day 1 plus leucovorin 20 mg/m(2) over 10 min, followed by a 5-fluorouracil (5-FU) bolus 400 mg/m(2) and 22 h of continuous infusion of 600 mg/m(2) on days 1-2. Treatment was repeated in 2-week intervals. The levels of serum VEGF and IGF-1 were measured using enzyme-linked immunoassays.
  
  
  RESULTS
  There was a significant correlation between the serum level of VEGF and Lauren's classification (p = 0.030) and previous operations (p = 0.010). IGF-1 was associated with the number of metastases (p = 0.012). The median level of serum VEGF was decreased after FOLFOX chemotherapy (p = 0.034). However, none of the measured serum markers were significantly correlated with response. In univariate analysis, overall survival (p < 0.001) was significantly shorter in patients with high serum levels of VEGF. Multivariate analysis revealed that VEGF was an independent factor for overall survival (HR 2.221; 95% CI 1.377-3.583, p = 0.001). Furthermore, IGF-1 had no significant influence on the clinical outcome.
  
  
  CONCLUSIONS
  A high level of serum VEGF is an independent prognostic factor in patients with advanced gastric cancer treated with chemotherapy. This may help to identify the patients who are more sensitive to the FOLFOX regimen.
authors.affiliation: Department of Internal Medicine, Dong-A University College of Medicine, Busan 602-715, Korea.
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Oh
authors.forename: Hyuk-Chan
authors.initials: HC
authors.lastname: Kwon
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Suee
authors.initials: S
authors.lastname: Lee
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Christian A
authors.initials: CA
authors.lastname: Graves
authors.forename: Kevin
authors.initials: K
authors.lastname: Camphausen
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D009944:Organoplatinum Compounds; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I; D002955:Leucovorin; D005472:Fluorouracil