Phase II study of combination doxorubicin, interferon-α, and high-dose tamoxifen treatment for advanced hepatocellular carcinoma

Background/Aims: Our previous studies showed that high-dose tamoxifen may improve the therapeutic efficacy of doxorubicin (HTD regimen) in hepatocellular carcinoma. Interferon-α, either as a single-agent treatment or as a biochemical modulator, has also been reported to be effective in the treatment of hepatocellular carcinoma. In this study, we sought to clarify if the addition of Interferon-α2b to HTD regimen could further improve the control of advanced hepatocellular carcinoma. Methodology: Eligible patients had unresectable and non-embolizable hepatocellular carcinoma, objectively measurable tumors, adequate hemogram and major organ function, age ?75 year, and a Karnofaky performance status ?60%. The treatment included oral tamoxifen 40mg/m2, q.i.d, Day 1-7; interferon-α2b subcutaneous injection, 5MU/m2, q.d. (Day 3-5) and 3MU/m2, q.o.d. (Day 6-21); and intravenous doxorubicin 60mg/m2, Day 4, repeated every 4 weeks. Results: From May 1997 through July 2002, a total of 30 patients were enrolled, 25 of whom were eligible for assessment of response and toxicity. These included 20 men and 5 women, with a median age of 45 years. They received an average of 3.5 (range: 1-8) courses of chemotherapy. Grade 3-4 leukopenia and Grade 3-4 thrombocytopenia developed in 46.7% and 51.0% of treatment courses, respectively. Gastrointestinal toxicity was generally mild. One patient achieved a complete remission and remained disease-free at this report, with a progression-free survival of 49 months at last follow-up in September 2002. Five patients achieved a partial remission, with a median progression-free survival of 7 months. The total response rate was 24% (95% confidence interval 9.4-45.1%). Median survival for all 25 patients was 6.0 months and the 1-year survival rate was 16%. Conclusions: Combination of interferon-α2b, high-dose tamoxifen, and doxorubicin is an effective treatment for advanced hepatocellular carcinoma. However, the data does not support that addition of interferon-α2b is superior to HTD regimen alone.