Phase I clinical trial of liposomal daunorubicin in hepatocellular carcinoma complicating liver cirrhosis.
Chemotherapy has been proposed for patients with hepatocellular carcinoma (HCC) associated with well-compensated cirrhosis who are unsuitable for locoregional treatments. Anthracyclines are the most active agents against HCC, although their toxicity is often unpredictable; thus, there is a need for new active drugs with a safe toxicity profile. The liposomal formulation of the anthracycline daunorubicin has low systemic toxicity and is taken up strongly by the liver. We started a phase I study with liposomal daunorubicin (starting dose 80 mg/m2 every 21 days) in patients with hepatocellular carcinoma and Child-Pugh stage A or B liver cirrhosis. At the starting dose, we recorded dose-limiting toxicities (1 hyperbilirubinemia, 1 prolonged prothrombin time, 1 persisting grade 3 neutropenia) in 3 out of 4 patients. Thus, according to protocol, we went down to the dose level of 60 mg/m2 but still 2 out of 3 patients had unacceptable toxicity (1 hypertransaminasemia, 1 hyperbilirubinemia with encephalopathia). Finally, we treated 4 more patients at the dose level of 40 mg/m2 and again we recorded liver toxicity in three of them. Overall haematological toxicity was mild and significant non-haematologic toxicities, other than hepatic, were not recorded. The toxicity profile observed warns against further assessment of liposomal daunorubicin in patients with hepatocellular carcinoma and liver cirrhosis.
Daniele
B
B
Division of Medical Oncology B, National Cancer Institute, Napoli, Italy.
De Vivo
R
R
Perrone
F
F
Lastoria
S
S
Tambaro
R
R
Izzo
F
F
Fiore
F
F
Vallone
P
P
Pignata
S
S
D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004337:Drug Carriers; D005260:Female; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D008081:Liposomes; D008103:Liver Cirrhosis / Q000150:complications*; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011517:Prothrombin Time
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D003630:Daunorubicin