Phase II study of gemcitabine in patients with advanced hepatocellular carcinoma

Abstract

BACKGROUND The objective of this study was to evaluate the efficacy and toxicity of gemcitabine in patients with chemotherapy‐naïve, 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. Cancer 2000;89:750–6. © 2000 American Cancer Society.

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

“…Many small-scale trials of combining MTT with cytotoxic chemotherapy have been reported [385][386][387][388][389]. However, the treatment efficacy in terms of tumor response rate and patient survival were similar to those reported for the cytotoxic regimens alone (Table 3) [372,[375][376][377][378][379][380][381][382]. A second approach is to combine MTT targeting different molecular pathways.…”

“…However, 25% of patients died of doxorubicin-related complications, including infection and cardiotoxicity. The antitumor activity of newer cytotoxic agents, such as gemcitabine [378,379], oxaliplatin [380], and capecitabine [381], has been modest, with single-agent tumor response rate of 10% or less ( Table 2). The most common grade 3-4 toxicity was myelosuppression, which occurred in 10-40% of the patients.…”

Hepatocellular carcinoma (HCC): beyond sorafenib—chemotherapy

“…Therefore, based on pre-clinical rationale gemcitabine was evaluated in patients with advanced HCC. In a phase II study of gemcitabine in treatment-naive patients with advanced HCC, 5 patients (18%) had objective responses with mild toxicities (17). However, two subsequent phase II studies of gemcitabine failed to show meaningful clinical efficacy [0-5% overall response rate (ORR)] (18,19).…”

Current management of hepatocellular carcinoma: An Eastern perspective

“…Notably, 25% of patients died due to doxorubicinrelated complications, including septicemia and cardiotoxicity. The antitumor activity of other cytotoxic agents such as gemcitabine [62,63] , oxaliplatin [64] , and capecitabine [65] in clinical and retrospective studies was modest with objective responses of < 20%. In randomized controlled trials, combination therapies such as PIAF (cisplatin, interferon, adriamycin, fluorouracil) and FOLFOX (5-fluorouracil, folic acid, and oxaliplatin) did not significantly improve survival compared with doxorubicin [59,60] .…”