Pegylated liposomal doxorubicin in treating a case of advanced hepatocellular carcinoma with severe hepatic dysfunction and pharmacokinetic study

Abstract

There is lack of effective and safe chemotherapy for advanced hepatocellular carcinoma. Polyethylene glycol-coated (pegylated) liposomal doxorubicin (PLD) has long circulation time and enhanced drug accumulation in the tumor tissues. It has significant activity in Kaposi's sarcoma, breast and ovarian cancers and the acute adverse effects of free drug are reduced. A patient with advanced hepatocellular carcinoma was treated with PLD and a pharmacokinetic study was performed. Initial serum total and direct bilirubin were 3.6 and 6.8 folds of upper normal, respectively, and an indocyanine green clearance test at 15 minutes was 26.3% (normal < 15%). Compared to cases with normal liver function, increased volume of distribution of doxorubicin correlated with a large amount of ascites (P < 0.05). The clearance of drug was unexpectedly higher than in cases with normal liver function (P < 0.05). According to the pharmacokinetic studies, the disposition of PLD in this case has not been retarded even in the presence of severe liver dysfunction. Only minimal toxicities including grade 2 stomatitis and moderate leukopenia were observed. The tumor had a partial remission and the patient survived nine months after PLD treatment. PLD could serve as a safe and effective treatment for hepatocellular carcinoma even in the presence of impaired liver function. Its role in treating advanced hepatocellular carcinoma is worthy of further study.