title: Administration of adjuvant oral tegafur/uracil chemotherapy post hepatocellular carcinoma resection: A randomized controlled trial.
abstract: BACKGROUND
  Recurrence of hepatocellular carcinoma (HCC) after surgery is frequent, and is an important factor adversely influencing the long-term survival of patients. This prospective study evaluated whether adjuvant chemotherapy with oral tegafur/uracil (UFT) reduces the recurrence rate of HCC. In addition, expression of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) were investigated in resected tumors and nontumorous tissues, and the relationship between their expression and the effectiveness of UFT was examined.
  
  
  METHODS
  A total of 117 patients who underwent curative hepatic resection for HCC were randomly allocated to UFT 400 mg/d (n = 24, UFT group) or surgery alone (n = 56, control group). The primary endpoint was the recurrence-free survival rate, and the secondary endpoint was the overall survival rate. Expression of the DPD and TS genes were quantified with TaqMan reverse transcription-polymerase chain reaction assay using β-actin as an internal standard. The cut-off value was set at the mean value of TS and DPD expression.
  
  
  RESULTS
  Among the 61 patients in the UFT group, 37 patients (60.6%) discontinued UFT within 1 month. Recurrence-free survival (p = 0.16) and overall survival (p = 0.29) were similar in the two groups. In the UFT group, recurrence-free survival did not differ significantly between high-TS (TS > 3.6) and high-DPD (DPD > 8.9; n = 10), and low-TS (TS ≤ 3.6) and low-DPD (DPD ≤ 8.9; n = 9) groups. However, there was a significant difference between the two groups in overall survival (p = 0.04).
  
  
  CONCLUSIONS
  Peroral UFT administration fails to prolong the recurrence-free rates and overall survival rates, in comparison with surgery alone. However, oral administration of UFT may improve the survival of HCC patients when the levels of TS and DPD mRNA are low in the tumor tissue.
authors.affiliation: Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi, Japan. Electronic address: mm-ishizuka@umin.ac.jp.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ishizuka
authors.affiliation: Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kubota
authors.affiliation: Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Nemoto
authors.affiliation: Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Mitsugi
authors.initials: M
authors.lastname: Shimoda
authors.affiliation: Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Iso
authors.affiliation: Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Tago
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000517:prevention & control*; D011446:Prospective Studies; D016019:Survival Analysis; D005641:Tegafur / Q000627:therapeutic use; D016896:Treatment Outcome; D014498:Uracil / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D005641:Tegafur; D014498:Uracil
keywords: dihydropyrimidine dehydrogenase; hepatocellular carcinoma; thymidylate synthase