Evaluation of the Change of Outcomes over a Ten-Year Period in Patients with Stage III Colon Cancer: Pooled Analysis of 6501 Patients Treated with Fluorouracil, Leucovorin, and Oxaliplatin in the ACCENT Database

Abstract Background The adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX or FLOX) have been the standard of care for resected colon cancer patients since 2004. Herein, we examined the change of outcomes over a ten-year period in stage III colon cancer patients who received this regimen. Patients and Methods Individual patient data from the ACCENT database was used to compare the outcomes in an older (1998-2003) and newer (2004-2009) treatment eras of patients with stage III colon cancer who received adjuvant FOLFOX or FLOX. Outcomes were compared between the two groups by multivariate Cox proportional hazards model adjusting for age, gender, performance score, T stage, N stage, tumor sidedness, and histological grade. Results A total of 6501 stage III patients, who received adjuvant FOLFOX or FLOX in six randomized trials, were included in the analysis. Patients enrolled in the newer era experienced statistically significantly improved time-to-recurrence (three-year rate, 76.1% versus 73.0%; adjusted hazard ratio [HRadj]=0.83, [95% CI, 0.74-0.92], P=0.0008), disease-free survival (DFS, three-year rate, 74.7% versus 72.3%; HRadj=0.88 [0.79-0.98], P=0.024), survival after recurrence (SAR, median time, 27.0 versus 17.7 months; HRadj=0.65 (0.57-0.74), P Conclusion Improved outcomes were observed in stage III colon cancer patients enrolled in clinical trials who received adjuvant FOLFOX/FLOX therapy in 2004 or later compared to older era. Prolonged SAR calls for re-validation of three-year DFS as the surrogate endpoint of OS in adjuvant clinical trials, and re-evaluation of optimal follow-up of OS to confirm trial findings based on DFS endpoints.