title: Uracil-tegafur as an adjuvant for hepatocellular carcinoma: a randomized trial.
abstract: Frequent recurrence of hepatocellular carcinoma (HCC) after surgery remains a major clinical problem. This randomized controlled trial evaluated whether postoperative adjuvant therapy with oral uracil-tegafur (UFT) prevents recurrence of HCC. A total of 160 patients who underwent curative hepatic resection for HCC were randomly assigned to receive either 300 mg/day of UFT for 1 year after surgery (n = 79, UFT group) or surgery alone (n = 80, control group). The primary endpoint was recurrence-free survival, and the secondary endpoint was overall survival. Other study variables included liver function and type of recurrence. During a median follow-up of 4.8 years (range: 0.5-7.9), recurrence-free survival curves in the groups were similar (P = .87). Overall survival was slightly but not significantly worse in the UFT group than in the control group (P = .08). The rates of recurrence-free and overall survival at 5 years were 29% and 58%, respectively, in the UFT group, as compared with 29% and 73%, respectively, in the control group. The hazard ratio for recurrence in the UFT group, relative to the control, was 1.01 (95% confidence interval: 0.84-1.22, P = .87). The proportion of patients with advanced recurrence (i.e., multiple, extrahepatic, or associated with vascular invasion) was significantly higher in the UFT group (74%, 43 of 58 patients with recurrence) than in the control group (53%, 30 of 57) (P = .02). In conclusion, our results offer no evidence to support potential benefits of adjuvant chemotherapy with UFT after surgery in patients with HCC and suggest that such treatment may even worsen overall survival.
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, University of Tokyo, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Tadatoshi
authors.initials: T
authors.lastname: Takayama
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Ijichi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Matsuyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imamura
authors.forename: Keiji
authors.initials: K
authors.lastname: Sano
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sugawara
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kokudo
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Makuuchi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage*; D014498:Uracil / Q000627:therapeutic use*
chemical_list: D005641:Tegafur; D014498:Uracil