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

    Research output: Contribution to journalArticle

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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

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    interferon alfa-2b
    Hepatocellular Carcinoma
    Observation
    Recurrence
    Hepatitis
    Therapeutics
    Survival
    Confidence Intervals
    Incidence
    Leukopenia
    Hepatitis B Surface Antigens
    Thrombocytopenia
    Antiviral Agents
    Meta-Analysis

    ASJC Scopus subject areas

    • Surgery

    Cite this

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

    In: Annals of Surgery, Vol. 255, No. 1, 2012, p. 8-17.

    Research output: Contribution to journalArticle

    Chen, LT, Chen, MF, Li, LA, Lee, PH, Jeng, LB, Lin, DY, Wu, CC, Mok, KT, Chen, CL, Lee, W-C, Chau, GY, Chen, YS, Lui, WY, Hsiao, CF, Whang-Peng, J & Chen, PJ 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, vol. 255, no. 1, pp. 8-17. https://doi.org/10.1097/SLA.0b013e3182363ff9
    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. / Long-term results of a randomized, observation-controlled, phase III Trial of Adjuvant Interferon alfa-2b in hepatocellular carcinoma after curative resection. In: Annals of Surgery. 2012 ; Vol. 255, No. 1. pp. 8-17.
    @article{2ae6aa279d9b498fbdbf27afb55ad7d5,
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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.",
    author = "Chen, {Li Tzong} and Chen, {Miin Fu} and Li, {Lung An} and Lee, {Po Huang} and Jeng, {Long Bin} and Lin, {Deng Yn} and Wu, {Cheng Chung} and Mok, {King Tong} and Chen, {Chao Long} and Wei-Chen Lee and Chau, {Gar Yang} and Chen, {Yaw Sen} and Lui, {Wing Yui} and Hsiao, {Chin Fu} and Jacqueline Whang-Peng and Chen, {Pei Jer}",
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    TY - JOUR

    T1 - Long-term results of a randomized, observation-controlled, phase III Trial of Adjuvant Interferon alfa-2b in hepatocellular carcinoma after curative resection

    AU - Chen, Li Tzong

    AU - Chen, Miin Fu

    AU - Li, Lung An

    AU - Lee, Po Huang

    AU - Jeng, Long Bin

    AU - Lin, Deng Yn

    AU - Wu, Cheng Chung

    AU - Mok, King Tong

    AU - Chen, Chao Long

    AU - Lee, Wei-Chen

    AU - Chau, Gar Yang

    AU - Chen, Yaw Sen

    AU - Lui, Wing Yui

    AU - Hsiao, Chin Fu

    AU - Whang-Peng, Jacqueline

    AU - Chen, Pei Jer

    PY - 2012

    Y1 - 2012

    N2 - 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.

    AB - 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.

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