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 received a liposomal formulation of daunorubicin (DaunoXome) at a dose equivalent to 100 mg/m2 of the free drug every 3 weeks. Altogether, 12 patients were assessable for response; 2 patients had stable disease for 8 weeks, but all eventually developed progressive disease and there was no responder. The drug was well tolerated, with no evidence of cardiac toxicity being observed. Deterioration of liver-function tests was attributed to progressive tumors in the terminal stage of the disease. Pharmacokinetics studies revealed 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 clearance of 15.0+/-5.5 ml/min. The AUC ratio between the metabolite daunorubicinol and daunorubicin was 0.07. These data differ markedly from the pharmacokinetics of the free drug.
Yeo
W
W
Department of Clinical Oncology, Chinese University of Hong Kong, Shatin, NT.
Chan
K K
KK
Mukwaya
G
G
Ross
M
M
Leung
W T
WT
Ho
S
S
Chan
A T
AT
Johnson
P J
PJ
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D003630:Daunorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008081:Liposomes; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D003630:Daunorubicin