Background: NSABP C-06 reported the non-inferiority of oral adjuvant uracil and tegafur plus leucovorin (UFT/LV) to weekly fluorouracil and folinate (5-FU/LV) in disease-free survival (DFS) in stage II/III CC. Although adjuvant FOLFOX for stage III is standard care in US or EU, its toxicity and cost is major problem. This is the first report of JCOG0205, which compared UFT/LV to standard 5-FU/levofoloinate (l-LV) in stage III CC. Methods: Pts were randomized to 3 courses of 5-FU/l-LV (5-FU 500 mg/m², l-LV 250 mg/m², on days 1, 8, 15, 22, 29, 36, q8w), or 5 courses of UFT/LV (UFT 300 mg/m²/day, LV 75 mg/day, on days 1–28, q5w). Primary endpoint was DFS. Sample size was 1,100, determined with one-sided alpha of 0.05, power of 0.78, and non-inferiority margin of hazard ratio (HR) of 1.27. Owing to interim analyses, the multiplicity-adjusted alpha and confidence coefficient of CI in the final analysis were 0.0433 and 91.3%. Results: Between Feb 2003 and Nov 2006, 1,101 pts (1,092 eligible) were randomized to 5-FU/l-LV (n=550) or UFT/LV (n=551). Median follow-up was 72.0 months, median age: 61, colon/rectum: 67%/33%, number of positive nodes <3/4<: 73%/27%, stage IIIa/IIIb: 75%/25%. The HR of DFS was 1.02 (91.3% CI, 0.84–1.23) and non-inferiority of UFT/LV was demonstrated (P=0.0236). Incidences of G3/4 toxicities were 8.4% neutropenia in 5-FU/l-LV and 8.7% ALT elevation in UFT/LV. In the 2 arms (5-FU/l-LV, UFT/LV), diarrhea (9.6%, 8.5%) and anorexia (4.0%, 3.7%) were similar. G3/4 diarrhea was one-third less and G3/4 ALT elevation was three times more common than those in C-06. No treatment-related death was reported. Conclusions: Adjuvant UFT/LV is demonstrated to be non-inferior to standard 5-FU/l-LV in DFS. Five-year OS (87.5%) is favorable to 69.6% in C-06, possibly due to D3 dissection and stage migration. UFT/LV should be an oral treatment option for stage III CC.

	5-FU/l-LV	UFT/LV	Overall
N	546	546	1,092
3Y DFS (%)	79.3	77.8	78.6
5Y DFS (%)	74.3	73.6	73.9
5Y OS (%)	88.4	87.5	87.9
N	544	540	1,084
G3/4 neutropenia (%)	8.4	1.5	5.0
G3/4 ALT (%)	0.7	8.7	4.7
G3/4 diarrhea (%)	9.6	8.5	9.0