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Eur Rev Med Pharmacol Sci ; 24(6): 2994-3003, 2020 03.
Article in English | MEDLINE | ID: mdl-32271417

ABSTRACT

OBJECTIVE: To profile and correlate KRAS mutations with outcome in stage III colon cancer (CC) patients who underwent adjuvant chemotherapy following curative resection surgery. PATIENTS AND METHODS: In this retrospective study, eligible patients were those with resected stage III CC who underwent 6-months adjuvant chemotherapy, either with fluoropyrimidine monotherapy (FP) or with oxaliplatin-based regimens (O-FP). Disease-free survival (DFS) and overall survival (OS) were analyzed and computed using the Kaplan-Meier method and the log-rank test. RESULTS: The study population included 148 patients (n=65 FP and n=83 O-FP). We identified KRAS mutations in 41/148 (27%) patients, of which 18 (44%) received FP and 23 (56%) O-FP. Five-year DFS and OS were significantly higher in patients with KRAS wild-type vs. mutant [DFS: 78 vs. 56%, HR: 0.47 (95% CI: 0.25; 0.87), p=0.01; OS: 73 vs. 68%, HR: 0.44 (95% CI: 0.21; 0.88), p=0.01]. In patients treated with FP, the 5-year DFS and OS was significantly improved in the KRAS wild-type vs. mutant group, respectively [DFS: 80 vs. 43%, HR: 2.88 (95% CI: 0.67; 3.76), p=0.014; OS: 85 vs. 68%, HR: 0.27 (95% CI: 0.10; 0.73), p=0.005]. Conversely, 5-year DFS and OS were not statistically different for patients with KRAS wild-type vs. mutations treated with O-FP, respectively [DFS: 78 vs. 65%, HR: 1.59 (95% CI: 0.67; 3.76), p=0.281; OS: 80 vs. 75%, HR: 0.73 (95% CI: 0.55; 2.12), p=0.57)]. CONCLUSIONS: Our results suggest that curatively resected stage III CC patients exhibiting wild-type KRAS status might benefit from FP alone. Conversely, an oxaliplatin-containing regimen should be recommended in KRAS mutated patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/therapy , Proto-Oncogene Proteins p21(ras)/genetics , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Colonic Neoplasms/diagnosis , Colonic Neoplasms/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Endonucleases/genetics , Endonucleases/metabolism , Female , Humans , Male , Middle Aged , Mutation , Neoplasm Staging , Proto-Oncogene Proteins p21(ras)/metabolism , Retrospective Studies
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