A twice-daily or a three-times-daily tegafur-uracil and leucovorin calcium regimen as adjuvant therapy in patients with resected colorectal cancer: A phase III study.

38 Background: Tegafur-uracil (UFT)/leucovorin calcium (LV) is an adjuvant chemotherapy treatment for colorectal cancer. We conducted a multicenter randomized trial to assess the noninferiority of a twice-daily compared with a three-times-daily UFT/LV regimen for stage II/III colorectal cancer in an adjuvant setting. Methods: Patients were randomly assigned to group A (three doses of UFT [300 mg/m2 per day]/LV [75 mg per day]) or B (two doses of UFT [300 mg/m2 per day]/LV [50 mg per day]). The schedule of 28-day oral administration followed by a 7-day rest period was repeated. Five 35-day cycles were repeated. The primary endpoint was 3-year disease-free survival. The secondary endpoints included 5-year overall survival and toxicity. Results: In total, 386 patients were enrolled between July 28, 2011, and September 27, 2013. The 3-year disease-free survival rates of group A (n = 194) and B (n = 192) were 79.4% and 81.4% (95% confidence interval, 72.6-84.4-74.5-85.9), respectively. The 5-year overall survival rates of group A and B were 89.7% and 91.0% (95% confidence interval, 83.3-92.8-84.8-93.8), respectively. The most common grade 3/4 adverse events in group A and B were diarrhea (3.9% vs. 7.3%), neutropenia (2.9% vs. 1.6%), increase in aspartate aminotransferase (4.0% vs. 3.9%), increase in alanine aminotransferase (6.2% vs. 6.8%), nausea (1.7% vs. 3.4%), and fatigue (1.1% vs. 2.3%). Conclusions: Group B outcomes were not inferior to group A outcomes, and adverse events did not increase. Clinical trial information: UMIN000005594.