Pegylated liposomal doxorubicin and gemcitabine in patients with advanced hepatocellular carcinoma

Abstract

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/m 2 on Days 1 and 8, followed by pegylated liposomal doxorubicin 30 mg/m 2 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. Cancer 2011;117:125-33.

Hepatocellular carcinoma (HCC): beyond sorafenib—chemotherapy

“…Another gemcitabine based combination chemotherapy, gemcitabine plus PLD treatment induced 10 objective clinical responses (24%) including 3 complete responses with median PFS of 5.8 months and median OS of 22.5 months in a phase II study (43). The results are very promising especially with the significantly improved median OS.…”

Good and Prolonged Response to Low Dose Capecitabine as Second Line Therapy in a Patient with Advanced Hepatocellular Carcinoma

“…Conversely, no standard treatment has been defined for patients who fail, are intolerant or not eligible for sorafenib. An interesting treatment was described by Lombardi et al [12], who treated forty-one patients with advanced HCC with a combination chemotherapy with gemcitabine 1000 mg/m² on days 1 and 8, followed by pegylated liposomal doxorubicin 30 mg/m² on day 1. They obtained three (7%) complete responses and seven (17%) partial responses.…”

“…First line therapy with pegylated liposomal doxorubicin and gemcitabine in the context of the trial by Lombardi et al [12], was administered from January to April 2009, for a total of 4 cycles. The radiological evaluation documented the partial response of the liver nodules and the reduction of the abdominal effusion.…”

Medical Management Options for Hepatocellular Carcinoma

“…There were three complete and seven partial responses (overall response rate 24 percent), the median TTP was 5.8 months, and median overall survival was 22.5 months. Treatment was well tolerated, with grade 3 to 4 toxicity limited to neutropenia (17 percent) and thrombocytopenia (2 percent) (Lombardi et al 2011). …”