title: Adjuvant Oral Uracil-Tegafur with Leucovorin for Colorectal Cancer Liver Metastases: A Randomized Controlled Trial.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Adjuvant therapy with UFT/LV effectively prolongs RFS after hepatic resection for CLM and can be recommended as an alternative choice.
  
  
  BACKGROUND
  UMIN Clinical Trials Registry C000000013.
authors: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Kiyoshi
authors: K
authors: Hasegawa
authors: Department of Gastrointestinal Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors: Akio
authors: A
authors: Saiura
authors: Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors: Tadatoshi
authors: T
authors: Takayama
authors: First Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
authors: Shinichi
authors: S
authors: Miyagawa
authors: Department of Surgery, National Defense Medical College, Tokorozawa, Japan.
authors: Junji
authors: J
authors: Yamamoto
authors: Department of Surgery, JCHO Tokyo Yamate Medical Center, Tokyo, Japan.
authors: Masayoshi
authors: M
authors: Ijichi
authors: Department of Surgery, Showa General Hospital, Tokyo, Japan.
authors: Masanori
authors: M
authors: Teruya
authors: Department of Surgery, Ibaraki Prefectural Central Hospital and Cancer Center, Ibaraki, Japan.
authors: Fuyo
authors: F
authors: Yoshimi
authors: Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
authors: Seiji
authors: S
authors: Kawasaki
authors: Department of Surgery, JCHO Tokyo Takanawa Hospital, Tokyo, Japan.
authors: Hiroto
authors: H
authors: Koyama
authors: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Masaru
authors: M
authors: Oba
authors: Department of Gastrointestinal Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors: Michiro
authors: M
authors: Takahashi
authors: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors: Nobuyuki
authors: N
authors: Mizunuma
authors: Department of Biostatistics, School of Public Health University of Tokyo, Tokyo, Japan.
authors: Yutaka
authors: Y
authors: Matsuyama
authors: Department of Surgical Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Toshiaki
authors: T
authors: Watanabe
authors: Department of Hepato-Biliary-Pancreatic Surgery, Japanese Red Cross Medical Center, Tokyo, Japan.
authors: Masatoshi
authors: M
authors: Makuuchi
authors: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Norihiro
authors: N
authors: Kokudo
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D005641:Tegafur / Q000627:therapeutic use*; D016896:Treatment Outcome; D014498:Uracil / Q000627:therapeutic use*
chemical_list: D005641:Tegafur; D014498:Uracil; D002955:Leucovorin