A Prospective Controlled Trial Of The Efficacy Of Uracil And Tegafur/Leucovorin For Stage Ii Colon Cancer With Risk Factors For Recurrence Using Propensity Score-Based Methods (Jfmc46-1201)

The usefulness of adjuvant chemotherapy for stage II colon cancer with high-risk factors for recurrence has not been established. Therefore, JFMC46 was conducted to evaluate the efficacy of adjuvant chemotherapy with uracil and tegafur/leucovorin (UFT/LV) for stage II colorectal cancer with risk factors. This was a prospective, non-randomized controlled study based on patients’ selection of treatment options, including randomized therapeutic decision-making. High-risk factors were defined as having at least one of the following factors: T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and <12 dissected lymph nodes. UFT (300 mg/m2/day) plus LV (75 mg/day) were orally administered; one course lasted 5 weeks, and 5 courses were administered. The primary endpoint was disease-free survival (DFS). The secondary endpoints were overall survival (OS) and safety. In total, 1938 patients were enrolled from 321 institutions in Japan between May 2012 and April 2016 (median follow-up period: 4.9 years). Eligible patients were divided into four groups: A, patients who selected surgery alone (n=641); B, patients who selected UFT/LV treatment (n=1239); C, patients who were assigned to surgery alone after randomization (n=18); D, patients who were assigned to UFT/LV treatment after randomization (n=17). Based on propensity score-matching, the 3-year DFS rates were 74.0% in group A (402 cases) and 80.9% in group B (804 cases) {hazard ratio [HR] 0.64 [95% confidence interval (CI) 0.50–0.83, P -0.0006]}. The 3-year OS rates were 94.7% in group A and 96.0% in group B [HR 0.79 (95% CI 0.51–1.22, P=0.2850)]. The median times to relapse were 8.9 months in group A and 16.2 months in group B. The incidence rates of adverse events of grade ≥3 in group B were 3.9% for diarrhea and 3.1% for liver dysfunction. However, the incidence was extremely low, and none were serious. Adjuvant chemotherapy with UFT/LV significantly improves DFS. Oral UFT/LV as adjuvant chemotherapy shows efficacy with an acceptable safety profile for stage II colon cancer with risk factors.