PURPOSE The primary objective of this randomized, multicenter, phase III trial was to investigate whether the addition of
irinotecan to the de Gramont infusional
fluorouracil (FU)/
leucovorin (LV) adjuvant regimen (LV5FU2) would improve disease-free survival (DFS) in patients with stage III
colon cancer. PATIENTS AND METHODS After curatively intentioned surgery, patients with stage II and III
colon cancer were randomly allocated surgery to receive LV5FU2 (LV 200 mg/m(2)
as a 2-hour infusion, followed by FU; as a 400 mg/m(2) bolus and then a 600 mg/m(2) continuous infusion over 22 hours, days 1 and 2, every 2 weeks for 12 cycles: de Gramont regimen) with or without
irinotecan (180 mg/m(2) as a 30- to 90-minute infusion, day 1, every 2 weeks). In total, 260 (7.9%) of 3,278 patients received an alternative high-dose infusional FU/LV regimen (Arbeitsgemeinschaft Internische Onkologie regimen) with or without
irinotecan. Results The principal efficacy analysis was based on 2,094 treated patients with stage III disease, randomly allocated in the LV5FU2 strata. After a median follow-up of 66.3 months, the 5-year DFS rate was 56.7% with
irinotecan/LV5FU2 and 54.3% with LV5FU2 alone (primary end point: log-rank P = .106). Combining
irinotecan with LV5FU2 did not significantly improve overall survival in this patient group compared with LV5FU2 alone (5-year rate 73.6% v 71.3%, respectively; log-rank P = .094). The addition of
irinotecan to LV5FU2 was associated with an increased incidence of grade 3 to 4 GI events and
neutropenia. CONCLUSION
Irinotecan added to LV5FU2 as adjuvant
therapy did not confer a statistically significant improvement in DFS or overall survival in patients with stage III
colon cancer compared with LV5FU2 alone.