Fig. 1.

Study design. Ascorbic acid was administered in both study parts with 5-FU continuous infusion. Standard mFOLOX6 comprised a standard dose of 85 mg/m² oxaliplatin on day 1 + leucovorin at 400 mg/m² (2-h infusion during oxaliplatin administration) + 5FU at 400 mg/m² (bolus immediately following irinotecan administration) and 2400 mg/m² (46-h continuous infusion), every 2 weeks. Standard FOLFIRI consisted of a standard dose of irinotecan at 180 mg/m2 (90-min infusion) + leucovorin 400 mg/m² (2-h infusion during irinotecan administration) + 5-FU at 400 mg/m2 (bolus immediately following irinotecan administration) and 2400 mg/m² (46-h continuous infusion), every 2 weeks. In part 1, AA was administered once daily at 180 min (part 1) or at a fixed rate of 0.6, 0.8 and 1 g/min (part 2) for three consecutive days with continuous 5-FU infusion in a 14-day cycle