Prognostic value of ERCC1, thymidylate synthase and glutathione S-transferase π for 5-FU/oxaliplatin chemotherapy in advanced colorectal cancer

Abstract

3607 Background: The aim of this study was to determine whether expressions of the excision cross-complementing (ERCC1), thymidylate synthase (TS) and glutathione S-transferase π (GSTπ) predict clinical outcome in patients with advanced colorectal cancer treated with fluorouracil (5-FU)/oxaliplatin chemotherapy. Methods: The study population consisted of 70 advanced colorectal cancer patients (median age, 53 years). Patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion at days 1 plus LV 20 mg/m2 over 10 minutes, followed by 5-FU bolus 400 mg/m2 and 22 hour continuous infusion of 600 mg/m2 at day 1–2. Treatment was repeated in 2 week intervals. The expressions of ERCC1, TS and GSTπ of primary tumors were examined by immunohistochemistry. Results: The positive rates of ERCC1, TS, and GSTπ were 55.7%, 68.6%, and 71.4%, respectively. The patients without TS expression were more likely to respond to chemotherapy (p=0.009). There were no significant differences between response and ERCC1 or GSTπ expression pattern (p=0.768, p=0.589, respectively). Median overall survival (OS) was significantly longer in patients without ERCC1 expression (p=0.0474). Patients with ERCC1 positive combined with TS positive, or those with ERCC1 positive combined with TS positive and GSTπ positive had poor OS (p=0.0017, p=0.0323, respectively). Multivariate analysis revealed that both ERCC1 and TS expression significantly impacted on OS (Hazard ratio 1.72, p=0.023). Conclusions: Immunohistochemical studies for ERCC1 and TS may be useful in prediction of the clinical outcome of advanced colorectal cancer patients treated with 5-FU and oxaliplatin. No significant financial relationships to disclose.