PLoS ONE (Jan 2016)

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

  • Kiyoshi Hasegawa,
  • Akio Saiura,
  • Tadatoshi Takayama,
  • Shinichi Miyagawa,
  • Junji Yamamoto,
  • Masayoshi Ijichi,
  • Masanori Teruya,
  • Fuyo Yoshimi,
  • Seiji Kawasaki,
  • Hiroto Koyama,
  • Masaru Oba,
  • Michiro Takahashi,
  • Nobuyuki Mizunuma,
  • Yutaka Matsuyama,
  • Toshiaki Watanabe,
  • Masatoshi Makuuchi,
  • Norihiro Kokudo

DOI
https://doi.org/10.1371/journal.pone.0162400
Journal volume & issue
Vol. 11, no. 9
p. e0162400

Abstract

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The 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).In 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).Between 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).Adjuvant therapy with UFT/LV effectively prolongs RFS after hepatic resection for CLM and can be recommended as an alternative choice.UMIN Clinical Trials Registry C000000013.