Expression of Bax Predicts Outcome in Advanced Gastric Cancer Patients Treated With 5-fluorouracil and Platinum Palliative Chemotherapy

Abstract

Purpose: The present study evaluated the predictive role of Bax, excision repair cross-complementation group 1 (ERCC1), and thymidylate synthase (TS) on clinical outcomes in patients with advanced gastric cancer treated with 5-fluorouracil (5-FU) and platinum palliative chemotherapy.

Materials and Methods: One hundred and twenty-eight patients with metastatic or recurrent gastric cancer were treated with a chemotherapy regimen of either 5-FU and heptaplatin (FH) (56 patients) or 5-FU, leucovorin, and oxaliplatin (FOLFOX) (72 patients). 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 49 (38%), 60 (47%), and 48 (38%) patients, respectively. The median overall survival (OS) of patients in total was 10 months. Low expression of Bax was associated with poor OS (median, 9 months vs. 12 months; 2-year, 7% vs. 32%; p=0.0005) in univariate analysis, while expression of ERCC1 and TS was not correlated with patient outcome. The outcome of patients with low expression of Bax was significantly worse in the FOLFOX group (median OS, 9 months vs. 18 months; p=0.0008), without significant difference in the FH group. In multivariate analysis, low expression of Bax was a significant independent predictor of poor OS (p=0.014).

Conclusions: Low expression of Bax was significantly associated with the poor survival of patients with metastatic or recurrent gastric cancer treated with 5-FU and platinum chemotherapy. Immunohistochemical staining for Bax with pretreatment biopsy specimen may be useful in selecting FOLFOX regimen as a treatment option for these patients.