title: Biological markers as a predictor for response and prognosis of unresectable gastric cancer patients treated with irinotecan and cisplatin.
abstract: BACKGROUND
  Previously we reported that immunohistochemical examination of p53, bcl-2, glutathione S-transferase-pi (GST-pi), thymidylate synthase (TS) and vascular endothelial growth factor (VEGF) in biopsy samples was a useful method for predicting clinical outcome of gastric cancer patients treated with 5-fluorouracil and cisplatin. Here, we investigated if these biological markers can predict chemoresponse and survival of unresectable gastric cancer patients treated with irinotecan and cisplatin.
  
  
  METHODS
  The subjects were 55 unresectable gastric cancer patients treated with irinotecan (70 mg/m(2), Days 1 and 15) and cisplatin (80 mg/m(2), Day 1). Expression of p53, bcl-2, VEGF was examined immunohistochemically in biopsy samples.
  
  
  RESULTS
  The overall response rate and the median survival time were 55% (30/55) and 321 days, respectively. Thirty patients with intestinal-type adenocarcinoma survived longer than 25 patients with diffuse-type (median survival time: 446, 259 days, P = 0.013). The favorable phenotypes for chemoresponse were p53-negative, bcl-2-negative and VEGF-positive, which were in accordance with previous findings. The response rate was significantly correlated with the total number of these favorable phenotypes (P = 0.043). The 39 patients having 2 or 3 favorable phenotypes (p53-negative, bcl-2-negative and VEGF-positive) survived longer than the remaining 16 patients (median survival time: 444, 259 days, P = 0.021). In the Cox model, the number of the favorable phenotypes showed a tendency to correlate with survival after adjustment for potentially prognostic factors such as histological type or performance status (P = 0.070).
  
  
  CONCLUSIONS
  Immunohistochemical examination of biological markers may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with irinotecan and cisplatin.
authors.affiliation: Division of Digestive Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan. fnagashi@saitama-med.ac.jp
authors.forename: Fumio
authors.initials: F
authors.lastname: Nagashima
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: Takahiro
authors.initials: T
authors.lastname: Hasebe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
authors.forename: Yu
authors.initials: Y
authors.lastname: Sakata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Miyata
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ando
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D051549:Glutathione S-Transferase pi / Q000032:analysis; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D000077146:Irinotecan; D051549:Glutathione S-Transferase pi; D002945:Cisplatin; D002166:Camptothecin