title: Long-term results of a randomized, observation-controlled, phase III trial of adjuvant interferon Alfa-2b in hepatocellular carcinoma after curative resection.
abstract: OBJECTIVE
  To investigate the clinical efficacy of adjuvant interferon alfa-2b (IFNα-2b) therapy on recurrence-free survival (RFS) of patients with postoperative viral hepatitis-related hepatocellular carcinoma (HCC).
  
  
  BACKGROUND
  Despite most individual trials have failed to meet their primary endpoint, recent pooled-data meta-analyses suggest that adjuvant IFN therapy may significantly reduce the incidence of recurrence in curatively ablated HCC.
  
  
  METHODS
  Patients with curative resection of viral hepatitis-related HCC were eligible, and were stratified by underlying viral etiology and randomly allocated to receive either 53 weeks of adjuvant IFNα-2b treatment or observation alone. The primary endpoint of this study was RFS.
  
  
  RESULTS
  A total of 268 patients were enrolled with 133 in the IFNα-2b arm and 135 in the control arm. Eighty percent of them were hepatitis B surface antigen seropositive. At a median follow-up of 63.8 months, 154 (57.5%) patients had tumor recurrence and 84 (31.3%) were deceased. The cumulative 5-year recurrence-free and overall survival rates of intent-to-treat cohort were 44.2% and 73.9%, respectively. The median RFS in the IFNα-2b and control arms were 42.2 (95% confidence interval [CI], 28.1-87.1) and 48.6 (95% CI, 25.5 to infinity) months, respectively (P = 0.828, log-rank test). Adjuvant IFNα-2b treatment was associated with a significantly higher incidence of leucopenia and thrombocytopenia. Thirty-four (24.8%) of treated patients required dose reduction, and 5 (3.8%) of these patients subsequently withdrew from therapy because of excessive toxicity. Adjuvant IFNα-2b only temporarily suppressed viral replication during treatment period.
  
  
  CONCLUSIONS
  In this study, adjuvant IFNα-2b did not reduce the postoperative recurrence of viral hepatitis-related HCC. More potent antiviral therapy deserves to be explored for this patient population. This study is registered at ClinicalTrials.gov and carries the identifier NCT00149565.
authors: National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan. leochen@nhri.org.tw
authors: Li-Tzong
authors: LT
authors: Chen
authors: Miin-Fu
authors: MF
authors: Chen
authors: Lung-An
authors: LA
authors: Li
authors: Po-Huang
authors: PH
authors: Lee
authors: Long-Bin
authors: LB
authors: Jeng
authors: Deng-Yn
authors: DY
authors: Lin
authors: Cheng-Chung
authors: CC
authors: Wu
authors: King-Tong
authors: KT
authors: Mok
authors: Chao-Long
authors: CL
authors: Chen
authors: Wei-Chen
authors: WC
authors: Lee
authors: Gar-Yang
authors: GY
authors: Chau
authors: Yaw-Sen
authors: YS
authors: Chen
authors: Wing-Yui
authors: WY
authors: Lui
authors: Chin-Fu
authors: CF
authors: Hsiao
authors: Jacqueline
authors: J
authors: Whang-Peng
authors: Pei-Jer
authors: PJ
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000401:mortality / Q000601:surgery; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use* / Q000633:toxicity; D007970:Leukopenia / Q000139:chemically induced; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000517:prevention & control; D019370:Observation; D010352:Patient Dropouts; D011994:Recombinant Proteins / Q000627:therapeutic use / Q000633:toxicity; D015996:Survival Rate; D013624:Taiwan; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins