title: Significance of biological markers for predicting prognosis and selecting chemotherapy regimens of advanced gastric cancer patients between continuous infusion of 5-FU and a combination of 5-FU and cisplatin.
abstract: BACKGROUND
  Our previous phase II study of 5-fluorouracil (5-FU) and cisplatin (FP) for treatment of advanced gastric cancer showed that strong immunoreactivity for vascular endothelial growth factor (VEGF) is associated with chemoresponse. Patients with four or five of the favorable phenotypes, p53 (-), bcl-2 (-), gluthathione S-transferase pi (-), thymidylate synthase (-), and VEGF (+), survived longer than those with three or less of these phenotypes. The purpose of this study is to confirm our previous results and to compare the significance of those markers between continuous infusion of 5-FU (5-FUci) and FP.
  
  
  METHODS
  Pretreatment biopsies from 131 of 210 advanced gastric cancer patients enrolled to JCOG9205 were analyzed immunohistochemically for the presence of the five markers.
  
  
  RESULTS
  Median survival times of patients treated with 5-FUci (n = 65) or FP (n = 66) were 216 and 253 days, respectively (P = 0.6953). After FP treatment, patients with four or five favorable phenotypes (n = 20) survived longer than those with three or less favorable phenotypes (n = 46) (334 days and 243 days, respectively; P = 0.0463), and the survival times of 34 and 32 patients with VEGF (-) and (+) were similar (269 days and 253 days, respectively; P = 0.6317). After 5-FUci, 30 patients with VEGF (+) survived for a shorter time than 35 patients with VEGF (-) (142 days and 302 days, respectively; P = 0.0043).
  
  
  CONCLUSIONS
  The number of favorable phenotypes is prognostic for gastric cancer patients treated with FP, and VEGF has a different impact on survival between treatment with 5-FUci and FP.
authors.affiliation: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan. n.boku@scchr.jp
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Yoshida
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Miyata
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000652:urine*; D015415:Biomarkers / Q000032:analysis*; D002945:Cisplatin / Q000008:administration & dosage; D017326:Clinical Trials, Phase III as Topic; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage*; D019254:Genes, bcl-2 / Q000235:genetics; D005982:Glutathione Transferase / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D013940:Thymidylate Synthase / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D015415:Biomarkers; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D013940:Thymidylate Synthase; D005982:Glutathione Transferase; D002945:Cisplatin; D005472:Fluorouracil