Impact of microsatellite instability and p53 expression on stage III colon cancer disease-free survival in patients treated by fluorouracil and leucovorin with or without oxaliplatin.

15017 Background: The addition of oxaliplatin to fluorouracil and leucovorin (FL) regimen was recently demonstrated to improve the adjuvant treatment of stage III colon cancer at the cost of an increased incidence in adverse effects (André et al, NEJM, 2004). The aim of the study was to determine the values of the tumor microsatellite instability (MSI) phenotype and p53 expression as markers to predict benefit from adjuvant chemotherapy of colon cancer by FL alone or with oxaliplatin (FOLFOX4).,MSI phenotype and p53 status were determined by immunohistochemistry (IHC) in a series of 192 consecutive stage III colon cancer patients, treated by either FL (n = 123) or FOLFOX4 (n = 69). The 2 groups of patients were well balanced concerning the main characteristics and prognostic factors. Disease-free survival (DFS) was analyzed according to the IHC results and to the treatment received.,Thirty tumors (15.6%) were MSI due a complete loss of MLH1, MSH2 or MSH6 expression and 97 tumors (51.1%) overexpressed p53 (p53). The addition of oxaliplatin to a regimen of FL significantly improved DFS in the group of 30 patients with MSI tumors regardless of p53 status (3-yr DFS : 100% vs 57.9%; Hazard ratio : 0.19, 95% CI 0.05 to 0.79; P = 0.02), while the benefit for the 162 patients with MSS tumors was not significant (3-yr DFS : 80.8% vs 73.3%; HR : 0.65, 95% CI 0.34 to 1.22; P = 0.18). However, among the 88 patients with MSS-p53 tumor, a significant benefit in DFS was observed in the group of patients treated by FOLFOX4 compared to FL regimen (3-yr DFS : 87.7% vs 69.8%; HR : 0.38, 95% CI 0.16 to 0.89; P = 0.03). By contrast, there was no detectable benefit of oxaliplatin in the group of 73 patients with MSS-p53 tumors (3-yr DFS : 71.8% vs 76.7%; HR : 1.22, 95% CI 0.47 to 3.22; P = 0.68).,This retrospective study suggests that adding oxaliplatin to FL improves DFS of patients with stage III colon cancer whose tumor displays MSI and/or overexpresses p53, but not that of patients with MSS-p53 tumors. These results should be confirmed in larger and prospective studies. No significant financial relationships to disclose.