Long-term results of a randomized, observation-controlled, phase III trial of adjuvant interferon Alfa-2b in hepatocellular carcinoma after curative resection

• Published in: Annals of surgery Vol. 255; no. 1; p. 8
• Main Authors: Chen, Li-Tzong, Chen, Miin-Fu, Li, Lung-An, Lee, Po-Huang, Jeng, Long-Bin, Lin, Deng-Yn, Wu, Cheng-Chung, Mok, King-Tong, Chen, Chao-Long, Lee, Wei-Chen, Chau, Gar-Yang, Chen, Yaw-Sen, Lui, Wing-Yui, Hsiao, Chin-Fu, Whang-Peng, Jacqueline, Chen, Pei-Jer
• Format: Journal Article
• Language: English
• Published: United States 01.01.2012
• Subjects: Antineoplastic Agents - therapeutic use; Antineoplastic Agents - toxicity; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - surgery; Chemical and Drug Induced Liver Injury - etiology; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Follow-Up Studies; Hepatectomy; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - mortality; Hepatitis B, Chronic - surgery; Humans; Interferon-alpha - therapeutic use; Interferon-alpha - toxicity; Leukopenia - chemically induced; Liver Neoplasms - drug therapy; Liver Neoplasms - mortality; Liver Neoplasms - surgery; Male; Middle Aged; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - prevention & control; Observation; Patient Dropouts; Recombinant Proteins - therapeutic use; Recombinant Proteins - toxicity; Survival Rate; Taiwan; Thrombocytopenia - chemically induced; Treatment Outcome; Viral Load; Virus Replication - drug effects
• ISSN: 1528-1140
• DOI: 10.1097/sla.0b013e3182363ff9

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). 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. 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. 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. 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.