Bax predicts outcome in gastric cancer patients treated with 5-fluorouracil, leucovorin, and oxaliplatin palliative chemotherapy

Dig Dis Sci. 2011 Jan;56(1):131-8. doi: 10.1007/s10620-010-1280-8. Epub 2010 May 26.

Abstract

Background: Platinum and 5-fluorouracil (5-FU)-based regimens have been used the most frequently in palliative chemotherapy for gastric cancer. The present study evaluated the prognostic significance of Bax, excision repair cross-complementation group 1 (ERCC1), and thymidylate synthase (TS) in advanced gastric cancer patients treated with 5-FU, leucovorin, and oxaliplatin (FOLFOX) palliative chemotherapy.

Methods: Seventy-two patients with metastatic or recurrent gastric cancer were treated with FOLFOX regimen. Pretreatment tumor biopsy specimens were analyzed for Bax, ERCC1, and TS expression by immunohistochemistry.

Results: High expression of Bax, ERCC1, and TS was observed in 31 (43%), 33 (46%), and 35 (49%) patients, respectively. The median overall survival (OS) of patients was 12 months. Low expression of Bax was associated with poor OS (median, 9 months vs. 18 months; 2-year, 10% vs. 48%; p=0.0005) in univariate analysis, while expression of ERCC1 and TS was not correlated with patient outcome. In multivariate analysis, low expression of Bax was a significant independent predictor of poor OS (p=0.028). Low expression of Bax was significantly associated with poor survival of patients with metastatic or recurrent gastric cancer treated with FOLFOX chemotherapy.

Conclusions: Immunohistochemical staining for Bax with pretreatment biopsy specimen may be useful in selecting FOLFOX regimen as a treatment option for advanced gastric cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Biopsy
  • DNA-Binding Proteins / metabolism
  • Endonucleases / metabolism
  • Female
  • Fluorouracil / administration & dosage
  • Gastric Mucosa / metabolism
  • Humans
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Predictive Value of Tests
  • Prognosis
  • Retrospective Studies
  • Stomach / pathology
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism*
  • Thymidylate Synthase / metabolism
  • Treatment Outcome
  • bcl-2-Associated X Protein / metabolism*

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Organoplatinum Compounds
  • bcl-2-Associated X Protein
  • Thymidylate Synthase
  • ERCC1 protein, human
  • Endonucleases
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol