Clinical impact of K-ras mutation in colorectal cancer patients treated with adjuvant FOLFOX

Abstract

K-ras proto-oncogene is commonly mutated in colorectal cancer (CRC) and has been associated with predictive markers for anti-EGFR (epidermal growth factor receptor) therapy. However, the prognostic role of K-ras status is still unclear. The aim of this study was to evaluate the association between k-ras status and addition of oxaliplatin to fluorouracil plus leucovorin (FOLFOX) chemotherapy in CRC patients with curative surgical resection. Sixty-six patients with stage II or III CRC were treated with FOLFOX or fluorouracil plus leucovorin (FL) followed by curative surgery between January 2004 and October 2007. K-ras status was assessed by direct sequencing. Fifteen patients (22.7%) had K-ras mutations of codon 12 (11/15) or codon 13 (4/15). There were no significant differences in clinicopathological parameters, such as age, sex, stage, or adjuvant regimen between the wild-type K-ras and mutant K-ras. With a median follow-up of 41.6 months (range 25.1-72.3 months), median disease-free survival (DFS) and overall survival (OS) were not reached. With regard to K-ras status, DFS and OS were not statistically different (P = 0.269 and P = 0.917, respectively). Even in the group treated with FOLFOX only, neither DFS (P = 0.651) nor OS (P = 0.265) was significantly different according to K-ras status. With the exception of tumor location in DFS and OS, no differences in other variables were observed. Proximal colon cancer patients had a longer DFS than distal CRC patients (P = 0.079); this trend was maintained only in the wild-type K-ras group (P = 0.051). These results showed that K-ras status was not associated with clinical outcome in patients treated with adjuvant FOLFOX.