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


METHODS
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.


RESULTS
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).


CONCLUSIONS
These results showed that K-ras status was not associated with clinical outcome in patients treated with adjuvant FOLFOX.
Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, School of Medicine, Seoul, Korea.
Myung Hee
MH
Chang
In Kyu
IK
Lee
Yoon
Y
Si
Kyu Sang
KS
Lee
In-Sook
IS
Woo
Jae Ho
JH
Byun
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003062:Codon; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery; D004252:DNA Mutational Analysis; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D011905:Genes, ras; D056726:Genetic Association Studies; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D000077150:Oxaliplatin; D000090063:Proto-Oncogene Mas; D012189:Retrospective Studies; D016019:Survival Analysis
D000970:Antineoplastic Agents; D003062:Codon; C000715470:MAS1 protein, human; D009944:Organoplatinum Compounds; D000090063:Proto-Oncogene Mas; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil