Phase II studies with DaunoXome in patients with nonresectable hepatocellular carcinoma: clinical and pharmacokinetic outcomes

A total of 14 Chinese patients with inoperable hepatocellular carcinoma rec eived a liposomal formulation of daunorubicin (DaunoXome) at a dose equival ent to 100 mg/m(2) of the free drug every 3 weeks, Altogether, 12 patients were assessable for response; 2 patients had stable disease for 8 weeks, bu t all eventually developed progressive disease and there was no responder. The drug was well tolerated, with no evidence of cardiac toxicity being obs erved. Deterioration of liver-function tests was attributed to progressive tumors in the terminal stage of the disease. Pharmacokinetics studies revea led a biexponential decay for daunorubicin in association with mean initial and terminal half-lives of 1.8 and 7.4 h. respectively, and a mean total c learance of 15.0 +/- 5.5 ml/min. The AUC ratio between the metabolite dauno rubicinol and daunorubicin was 0.07. These data differ markedly from the ph armacokinetics of the free drug.