Long-term results of a randomized, observation-controlled, phase III Trial of Adjuvant Interferon alfa-2b in hepatocellular carcinoma after curative resection

Li Tzong Chen, Miin Fu Chen, Lung An Li, Po Huang Lee, Long Bin Jeng, Deng Yn Lin, Cheng Chung Wu, King Tong Mok, Chao Long Chen, Wei-Chen Lee, Gar Yang Chau, Yaw Sen Chen, Wing Yui Lui, Chin Fu Hsiao, Jacqueline Whang-Peng, Pei Jer Chen

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    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.

    Original languageEnglish
    Pages (from-to)8-17
    Number of pages10
    JournalAnnals of Surgery
    Volume255
    Issue number1
    DOIs
    Publication statusPublished - 2012

    ASJC Scopus subject areas

    • Surgery

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  • Cite this

    Chen, L. T., Chen, M. F., Li, L. A., Lee, P. H., Jeng, L. B., Lin, D. Y., Wu, C. C., Mok, K. T., Chen, C. L., Lee, W-C., Chau, G. Y., Chen, Y. S., Lui, W. Y., Hsiao, C. F., Whang-Peng, J., & Chen, P. J. (2012). Long-term results of a randomized, observation-controlled, phase III Trial of Adjuvant Interferon alfa-2b in hepatocellular carcinoma after curative resection. Annals of Surgery, 255(1), 8-17. https://doi.org/10.1097/SLA.0b013e3182363ff9