Administration Method of Adjuvant Tegafur‐Uracil and Leucovorin Calcium in Patients with Resected Colorectal Cancer: A Phase III Study

LESSONS LEARNED: The 3‐year disease‐free survival rate of the twice‐daily regimen was not inferior to that of the conventional three‐times‐daily regimen, and the twice‐daily regimen did not lead to an increase in adverse events. The effectiveness of the twice‐daily regimen highlights an increased number of treatment options for patients. This will facilitate personalized medicine, particularly for elderly or frail patients who may experience more severe side effects from the combination therapy. 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/m(2) per day]/LV [75 mg per day]) or B (two doses of UFT [300 mg/m(2) per day]/LV [50 mg per day]). The primary endpoint was 3‐year disease‐free survival. 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 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%). CONCLUSION: Group B outcomes were not inferior to group A outcomes, and adverse events did not increase.