Long-Term Results of a Randomized, Observation-Controlled, Phase III Trial of Adjuvant Interferon Alfa-2b in Hepatocellular Carcinoma Underwent Curative Resection.
Author(s): Chen LT, Chen MF, Li LA, Lee PH, Jeng LB, Lin DY, Wu CC, Mok KT, Chen CL, Lee WC, Chau GY, Chen YS, Lui WY, Hsiao CF, Whang-Peng J, Chen PJ
Affiliation(s): *National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan daggerDepartment of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan double daggerDepartment of Internal Medicine, National Cheng-Kung University Hospital, Tainan, Taiwan section signDepartment of Surgery, Chang-Gung Memorial Hospital-Lin-Kou and Chang-Gung University, Taoyuan, Taiwan paragraph signInstitute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan parallelInstitute of Statistical Science, Academia Sinica, Taipei, Taiwan **Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan daggerdaggerDepartment of Surgery, China Medical University Hospital, Taichung, Taiwan double daggerdouble daggerDepartment Internal Medicine, Chang-Gung Memorial Hospital-Lin-Kou and Chang-Gung University, Taoyuan, Taiwan section sign section signDepartment of Surgery, Veterans General Hospital, Taichung, Taiwan paragraph sign paragraph signDepartment of Surgery, Veterans General Hospital, Kaohsiung, Taiwan ***Department of Surgery, Chang-Gung Memorial Hospital, Kaohsiung, Taiwan daggerdaggerdaggerDepartment of Surgery, Veterans General Hospital, Taipei, Taiwan double daggerdouble daggerdouble daggerDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan section sign section sign section signGraduate Institute of Clinical Medicine, National Taiwan University, College of Medicine, Taipei, Taiwan paragraph sign paragraph sign paragraph signCenter of Excellency for Cancer Research, Taipei Medical University, Taipei, Taiwan.
Publication date & source: 2011-11-19, Ann Surg., [Epub ahead of print]
OBJECTIVE:: To investigate the clinical efficacy of adjuvant interferon alfa-2b (IFNalpha-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 IFNalpha-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 IFNalpha-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 IFNalpha-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 IFNalpha-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 IFNalpha-2b only temporarily suppressed viral replication during treatment period. CONCLUSIONS: In this study, adjuvant IFNalpha-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.