Controlled clinical trial of doxorubicin and tamoxifen versus tamoxifen monotherapy in hepatocellular carcinoma

OBJECTIVES: Treatment results of advanced hepatocellular carcinoma have remained unsatisfactory; the response rates to intravenous doxorubicin are no better than 20%. Oral tamoxifen has been proposed on the basis of beneficial results in some trials. The aim of this study was to evaluate whether the addition of doxorubicin to oral tamoxifen improves survival compared to oral tamoxifen alone. METHODS: Thirty-two consecutive patients with a priori defined contra-indications against surgery (transplantation, resection) or chemo-embolization were evaluated to receive chemotherapy. All patients received oral tamoxifen 30 mg bid; 16 also received intravenous doxorubicin 50 mg/m2 every 4 weeks. The control group consisted of the remaining 16 patients who either were considered unfit for doxorubicin because of a Karnofsky index < 50% (n = 5), cardiac disease (n = 6) or who refused to have cytotoxic drug therapy (n = 5). RESULTS: Median survival time was 148 days (95% CI 89.2-206.8) in the doxorubicin group and 96 days (95% CI 49.0-143.0) in the control group, and this was not significantly different (P= 0.408), regardless of the presence or absence of cirrhosis. CONCLUSIONS: In conclusion, the results of our study indicate that combination therapy using doxorubicin and tamoxifen is unlikely to considerably improve survival compared to tamoxifen alone in patients with advanced hepatocellular carcinoma.