Feasibility Report of a Randomized Multicenter Controlled Phase III Trial of Adjuvant UFT/LV Therapy after Resection for Liver Metastasis from Colorectal Carcinoma

ABSTRACT There is no established evidence yet to support the of postoperative adjuvant chemotherapy after resection of colorectal liver metastasis. A randomized multicenter controlled phase III trial was conducted and patients were recruited from 20 hospitals to compare the efficacy of postoperative adjuvant UFT/LV therapy (UTF: 300 mg/m2/day and LV: 75 mg/day, Day 1-28, once every 5 weeks, 5 cycles) with that of surgical monotherapy in patients with colorectal liver metastasis. A total of 180 patients enrolled from January 2004 to December 2010 are currently under follow-up. The primary endpoint is recurrence-free survival time and the secondary endpoint is overall survival time, the results of which are awaited. It is expected that the patients who underwent liver resection in this study are different from the stage II or III colon cancer patients treated by surgery for primary diseases. We shall report the results of the interim analysis of compliance and safety in the 175 patients for whom the CRFs relevant to this study could be collected. Eighty-eight patients received surgical monotherapy and 87 received surgery plus UFT/LV therapy. There were no significant differences in the demographic or clinicopathological factors between the two groups. The rate of completion of UFT/LV therapy (5 courses) was 53.8% (43/80), and the rates of completion up to 3 and 6 months were 71.3% (57/80) and 53.8% (43/80), respectively. The mean rate of dose intensity was 70.1%. Of the 37 patients in whom the treatment was discontinued, the reason for the discontinuation was adverse events in 26 patients (in conflict with discontinuation criteria in 7 patients and no conflict in 19) and appearance of recurrence in 8 patients. Adverse events of CTCAE grade 3 or higher observed in the UFT/LV Group included decrease in hemoglobin (3.8%), increase in AST/ATL (2.6%), febrile neutropenia (1.3%), hyperbilirubinemia (1.3%), diarrhea (5.0%), loss of appetite (2.5%), and nausea (2.5%). There were no treatment-related deaths. The incidence rates of these symptoms are not greatly different from those reported in relation to the safety profile after surgery for stage III colon cancer from the ACTS-CC study, which suggested that the tolerability of UFT/LV therapy was maintained even in stage IV colorectal cancer patients treated by hepatectomy. Disclosure All authors have declared no conflicts of interest.