Pegylated liposomal doxorubicin and gemcitabine in patients with advanced hepatocellular carcinoma: results of a phase 2 study.
BACKGROUND
Over the years, doxorubicin and gemcitabine have been among the most widely used drugs for hepatocellular carcinoma (HCC), with relative efficacy. The authors report the results of a phase 2 study of the combination of gemcitabine plus pegylated liposomal doxorubicin.


METHODS
Patients with advanced HCC received combination chemotherapy with gemcitabine 1000 mg/m² on Days 1 and 8, followed by pegylated liposomal doxorubicin 30 mg/m² on Day 1. Treatment was repeated every 4 weeks to a maximum of 8 cycles. Primary endpoint was overall response rate, and secondary endpoints were time to disease progression (TTP), overall survival (OS), and toxicity.


RESULTS
Forty-one patients were enrolled and were evaluable for response, toxicity, and survival. A total of 194 cycles of treatment were administered. Three (7%) patients had a complete response, and 1 of these patients underwent liver transplantation. Seven (17%) patients had a partial response and, among these patients, 1 patient underwent surgical resection. Among the 31 patients who had initial alpha-fetoprotein levels >400 ng/mL, 20 (64.5%) had a >20% decrease after 2 cycles of treatment. The median TTP and OS were 5.8 and 22.5 months, respectively. Hematologic toxicity was the most common side effect, including neutropenia (17%) and anemia (7%).


CONCLUSIONS
The combination of gemcitabine plus pegylated liposomal doxorubicin was active and safe in advanced HCC. Moreover, this treatment induced some complete responses and converted some untreatable HCCs into lesions eligible for resection or transplantation.
Department of Medical Oncology 1 Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy. lombardi.giuseppe.lg@gmail.com
Giuseppe
G
Lombardi
Fable
F
Zustovich
Fabio
F
Farinati
Umberto
U
Cillo
Alessandro
A
Vitale
Giacomo
G
Zanus
Martin
M
Donach
Miriam
M
Farina
Stefania
S
Zovato
Davide
D
Pastorelli
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D000093542:Gemcitabine
C506643:liposomal doxorubicin; D003841:Deoxycytidine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D000093542:Gemcitabine