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

Abstract

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/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 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.

Effects of sevoflurane and propofol on postoperative nausea and vomiting in patients with colorectal cancer placed under general anesthesia: a systematic review and meta-analysis

“…The eligible articles were searched individually to prevent omissions. Ultimately, a total of 12 RCTs (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) were included in this study, and there is no obvious selection risk bias in this study (see Table 1).…”

Reactive oxygen species mediated apoptotic death of colon cancer cells: therapeutic potential of plant derived alkaloids

“…Hence, in the current treatment regimen, this combination along with oral leucovorin has been included as a typical treatment for stage III colon cancer. Moreover, tegafur also shows serious side effects like neutropenia, thrombocytopenia, mucositis, and asthenia ( 65 , 66 ). Recently, regorafenib, a kinase inhibitor has been approved for the treatment of metastatic CRC.…”

Dihydropyrimidine Dehydrogenase-Mediated Resistance to 5-Fluorouracil: Mechanistic Investigation and Solution

“…Yen and co-workers reported comparable long-term outcomes among patients receiving adjuvant UFT monotherapy after a D2 gastrectomy (pathological stage II–IIIB (except T1) gastric cancer) . A clinical trial (UMIN000005594) was conducted on two groups, i.e., A and B, where group A received three doses of UFT (300 mg/m 2 per day)/LV (75 mg per day) and showed comparable outcomes to group B who received two doses of UFT (300 mg/m 2 per day)/LV (50 mg per day) with little change in adverse effects . All these reports support the UFT potential combination therapy for the quality treatment of resistance to cancer.…”