Phase II study of gemcitabine in patients with advanced hepatocellular carcinoma

BACKGROUND. The objective of this study was to evaluate the efficacy and to xicity of gemcitabine in patients with chemotherapy-naive, advanced hepatoc ellular carcinoma (HCC). METHODS. Twenty-eight patients with unresectable and nonembolizable HCC who had received no prior systemic chemotherapy and with objectively measurabl e tumors, adequate liver and renal function, and adequate bone marrow reser ve were enrolled on this study. The therapy consisted of gemcitabine 1250 m g/m(2) intravenously over 30 minutes weekly in an outpatient clinic. One co urse of treatment included three consecutive weekly infusions of gemcitabin e and a 1-week rest. Treatment courses were repeated every 4 weeks for a to tal of six courses unless there was prior evidence of progressive disease. RESULTS. All 28 patients were evaluable for response and toxicity. A partia l 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 dise ase (25%), and 16 patients had disease progression (57.2%). The median surv ival for all 28 patients was 18.7 weeks, and, for those patients who achiev ed a PR, it was 34.7 weeks. The median time to progression was 12 weeks. Na tional Cancer Institute Common Toxicity Criteria Grade 3-4 toxicity consist ed primarily of leucopenia (10.7%), anemia (14.3%), thrombocytopenia (10.7% ), and hepatotoxicity (14.3%). The spectrum of both hematologic and nonhema tologic toxicity was mild, with thrombocytopenia constituting the dose-limi ting side effect. CONCLUSIONS. Gemcitabine shows marginal antitumor activity in patients with advanced HCC, although the response duration is short-lived. Gemcitabine s eems to be particularly promising because of its low toxicity profile. Furt her studies in combination with other active agents are warranted. (C) 2000 American Cancer Society.