Phase II study of gemcitabine in patients with advanced hepatocellular carcinoma

BACKGROUND. The objective of this study was to evaluate the efficacy and toxicity of gemcitabine in patients with chemotherapy-naive, advanced hepatocellular carcinoma (HCC). METHODS. Twenty-eight patients with unresectable and nonembolizable HCC who had received no prior systemic chemotherapy and with objectively measurable tumors, adequate liver and renal function, and adequate bone marrow reserve were enrolled on this study. The therapy consisted of gemcitabine 1250 mg/m² intravenously over 30 minutes weekly in an outpatient clinic. One course of treatment included three consecutive weekly infusions of gemcitabine and a 1-week rest. Treatment courses were repeated every 4 weeks for a total of six courses unless there was prior evidence of progressive disease. RESULTS. All 28 patients were evaluable for response and toxicity. A partial response (PR) was achieved in 5 patients, for an overall response rate of 17.8% (95% confidence interval, 2.7-32.9%). Seven patients had stable disease (25%), and 16 patients had disease progression (57.2%). The median survival for all 28 patients was 18.7 weeks, and, for those patients who achieved a PR, it was 34.7 weeks. The median time to progression was 12 weeks. National Cancer Institute Common Toxicity Criteria Grade 3-4 toxicity consisted primarily of leucopenia (10.7%), anemia (14.3%), thrombocytopenia (10.7%), and hepatotoxicity (14.3%). The spectrum of both hematologic and nonhematologic toxicity was mild, with thrombocytopenia constituting the dose-limiting side effect. CONCLUSIONS. Gemcitabine shows marginal antitumor activity in patients with advanced HCC, although the response duration is short-lived. Gemcitabine seems to be particularly promising because of its low toxicity profile. Further studies in combination with other active agents are warranted. (C) 2000 American Cancer Society.