A phase II study of doxorubicin and cisplatin combination chemotherapy for advanced hepatocellular carcinoma

Background : There still is no standard treatment for the patients with advanced hepatocellular carcinoma. Both doxorubicin and cisplatin have modest activity with the response rates less than 20%, but have synergistic effect. This prospective phase II trial was performed to determine the efficacy and toxicity of doxorubicin and cisplatin combination chemotherapy for patients with advanced hepatocellular carcinoma. Methods : Patients with advanced hepatocellular carcinoma were entered into this study. Eligibility criteria are described below: histologically proven HCC or mass lesion on radiogram with liver cirrhosis and serum a-fetoprotein level400 ng/mL, UICC stage IV, recurred after and loco-regional treatment, no prior cytotoxic chemotherapy, measurable disease, ECOG performance scale 02, age 1865 year old, adequate bone marrow, cardiac and renal function, total bilirubin 3 mg/dL, Child’s hepatic risk A or B. Doxorubicin 50 mg/ and cisplatin 100mg/ on day 1 were administered intravenously every 3 weeks. This protocol was modified after enrollment of 16 patients due to toxicities. In the modified regimen, the dose of doxorubicin was reduced to 40 mg/ and cisplatin to 75 mg/. Results : Between January 1997 and August 2002, 23 patients were enrolled into this study. Among them, 21 patients were evaluable for response. 6 patients (28.6%, 95% CI: 8.948.1%) had an objective response. The median time to progression was 162 days. The median duration of survival was 144 days and 794 days in patients without response and with response, respectively. This difference was statistically significant. Four patients lived longer than a year. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 26.1% and 24.9% of all the cycles, respectively. Conclusion : Doxorubicin and cisplatin combination chemotherapy may be effective and may have survival benefit especially in the responders with acceptable toxicities.