Biological markers as a predictor for response and prognosis of unresectable gastric cancer patients treated with irinotecan and cisplatin

Jpn J Clin Oncol. 2005 Dec;35(12):714-9. doi: 10.1093/jjco/hyi194. Epub 2005 Nov 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Cisplatin / administration & dosage
  • Drug Administration Schedule
  • Female
  • Glutathione S-Transferase pi / analysis
  • Humans
  • Irinotecan
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / mortality
  • Tumor Suppressor Protein p53 / analysis
  • Vascular Endothelial Growth Factor A / analysis

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Vascular Endothelial Growth Factor A
  • Irinotecan
  • Glutathione S-Transferase pi
  • Cisplatin
  • Camptothecin