Adjuvant Oral Uracil-Tegafur with Leucovorin for Colorectal Cancer Liver Metastases: A Randomized Controlled Trial

Abstract

BackgroundThe high recurrence rate after surgery for colorectal cancer liver metastasis (CLM) remains a crucial problem. The aim of this trial was to evaluate the efficacy of adjuvant therapy with uracil-tegafur and leucovorin (UFT/LV).MethodsIn the multicenter, open-label, phase III trial, patients undergoing curative resection of CLM were randomly assigned in a 1:1 ratio to either the UFT/LV group or surgery alone group. The UFT/LV group orally received 5 cycles of adjuvant UFT/LV (UFT 300mg/m2 and LV 75mg/day for 28 days followed by a 7-day rest per cycle). The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included overall survival (OS).ResultsBetween February 2004 and December 2010, 180 patients (90 in each group) were enrolled into the study. Of these, 3 patients (2 in the UFT/LV group and 1 in the surgery alone group) were excluded from the efficacy analysis. Median follow-up was 4.76 (range, 0.15–9.84) years. The RFS rate at 3 years was higher in the UFT/LV group (38.6%, n = 88) than in the surgery alone group (32.3%, n = 89). The median RFS in the UFT/LV and surgery alone groups were 1.45 years and 0.70 years, respectively. UFT/LV significantly prolonged the RFS compared with surgery alone with the hazard ratio of 0.56 (95% confidence interval, 0.38–0.83; P = 0.003). The hazard ratio for death of the UFT/LV group against the surgery alone group was not significant (0.80; 95% confidence interval, 0.48–1.35; P = 0.409).ConclusionAdjuvant therapy with UFT/LV effectively prolongs RFS after hepatic resection for CLM and can be recommended as an alternative choice.Trial RegistrationUMIN Clinical Trials Registry C000000013

Oncological benefit of complete metastasectomy for simultaneous colorectal liver and lung metastases

“…24e26 Postoperative chemotherapy was administered in patients who were candidates for adjuvant chemotherapy for the primary disease and patients assigned to clinical trials (UMIN000007787 and UMIN000000013, http://www.umin.ac.jp/ctr/index.htm). 27 The patients were followed up after resection by obtaining their history and performing a physical examination, laboratory evaluation, and axial imaging every 3e4 months for the first 2 years and every 4e6 months for the subsequent 3 years. When recurrences were diagnosed, the treatment strategy was decided by multidisciplinary consensus.…”

Prognostic Impact of Adjuvant Chemotherapy after Hepatic Resection for Synchronous and Early Metachronous Colorectal Liver Metastases

“…For patients with CLM, however, only limited evidence is available. To date, several studies have reported that adjuvant chemotherapy prolonged recurrence-free survival (RFS) after resection of CLM using 5-fluorouracil with leucovorin (5-FU/LV) [5], FOLFOX [4], or uracil-tegafur (UFT; Taiho Pharmaceutical Co. Ltd., Tokyo, Japan), an oral 5-FU preparation combining tegafur and uracil, with LV (UFT/LV) [6]; however, none of them could show the improvement in overall survival (OS). Nevertheless, because of the high relapse rate even after the curative resection of CLM [7], adjuvant chemotherapy has been widely used in actual clinical settings considering the resected tumor burden or the performance status of patients.…”

“…Disease-free interval (DFI) from resection of primary lesion can be a factor estimating the risk of recurrence after heaptectomy for CLM [8]. However, definitions of synchronous and metachronous presentation vary among studies [4,6] and its influence on the efficacy of adjuvant chemotherapy has not well been studied so far.…”

Multidisciplinary Treatment for Colorectal Liver Metastases in Elderly Patients

“…However, their analysis of OS rather than DSS has made it di cult to interpret the result because senile weakness intolerant to adjuvant chemotherapy may have been directly associated with cancer-unrelated death in their assessment. Although administration of adjuvant chemotherapy after hepatectomy was not selected as a prognostic factor of DSS in univariate and multivariate analysis in the current study, a recent randomized trial demonstrated that adjuvant chemotherapy improves RFS in patients undergoing hepatectomy for CRLMs [27]. Additional studies are needed to investigate the prognostic impact of adjuvant chemotherapy, especially in older patients for whom the balance between therapeutic effect and toxicity is of great importance.…”