A Randomized Controlled Trial Evaluating Efficacy of Adjuvant Oral Uracil-Tegafur (uft) with Leucovorin (lv) after Resection of Colorectal Cancer Liver Metastases: the Uft/Lv Study.

3584 Background: Surgical resection has been accepted as the standard therapy for colorectal cancer liver metastases (CRLM), however, high recurrence incidence even after curative resection remains an unsolved problem. There is no established adjuvant chemotherapy for CRLM, although efficacy of several adjuvant treatments for stage III colorectal cancer has been confirmed. Oral UFT/LV is one of the standard therapies in stage III colorectal cancer. We conducted this randomized, open-label, phase III trial to evaluate efficacy of adjuvant UFT/LV therapy for CRLM (stage IV). Methods: A patient undergoing curative resection of CRLM was randomly assigned to either UFT/LV or surgery alone (control) group. In the UFT/LV group, 5 cycles of adjuvant UFT/LV (UFT 300mg/m2 and LV 75 mg/day for 28 days followed by 7 days rest in one cycle) were administered. The primary endpoint was relapse-free survival (RFS), while secondary endpoints were overall survival (OS) and safety. Results: Between February 2004 and December 2010, total 180 patients were enrolled to this trial, among whom 3 patients were ineligible for analysis. The baseline characteristics were well-balanced in the UFT/LV (n=88) and control (n=89) groups. Median follow-up was 4.76 years. The 3y-RFS rate in the UFT/LV group was 38.6%, which was significantly higher than the control group (32.3%). The hazard ratio for relapse in the UFT/LV relative to the control was 0.56 (95% confidence interval: 0.38-0.83, P=0.003). The 3y-OS rates were similar between the UFT/LV and control groups (82.8% vs. 81.6%, P=0.41). In the UFT/LV group without treatment-related death, the scheduled cycles was completed in 45 patients among 82 (54.9%), and the mean dose intensity ratio was 70.8%. As adverse events at any grade, hyperbilirubinemia (28.0%), liver dysfunction (23.2%), diarrhea (26.9%) and anorexia (28.0%) occurred. Conclusions: Adjuvant UFT/LV therapy is effective to prevent recurrence after surgical resection of CRLM. Clinical trial information: C000000013.