4270 Background: Few effective options are available for the treatment of unresectable HCC. Chemotherapy, in particular, has been of limited benefit. Several phase I trials suggest promising activity of a combination of gemcitabine and docetaxel. Methods: Patients with unresectable or metastatic HCC were treated with docetaxel 40 mg/m2 (later reduced to 30 mg/m2) and gemcitabine 800 mg/m2 on days 1, 8 every 3 weeks. A Simon study design called for accrual of 40 patients, with an interim analysis after 22, requiring at least 2 responses, with acceptable toxicity, to continue accrual. Results: 25 patients were enrolled in 26 months. Median age was 67 (range 27–78), 17 were male,15 had liver-only disease and10 had extrahepatic disease. 9 patients had cirrhosis, 6 viral hepatitis, and 1 hemachromatosis. Response –Of 21 patients evaluable for the primary endpoint (response), 2 (10%) have a confirmed response. TTP and Survival –The median TTP is 2.3 months (95% CI 1.3–5.6 months). Median survival is not yet reached with a median followup of 5.3 months (range 0–24 months). Toxicity –Two patients died on-study due to adverse events (1 hepatic and 1 renal failure), neither of which were attributed to the study medications. 17 patients (81%) have experienced grade 3+ adverse events, including 8 with grade 4+ adverse events. Hematologic toxicity and associated hemorrhage resulted in a reduction of the docetaxel dose. Conclusions: A response rate of 10% was observed in patients with HCC receiving gemcitabine and docetaxel. Patients experienced a high rate of grade 3+ toxicity including neutropenia and thrombocytopenia. Based on these results, accrual to the trial will not continue. The combination of gemcitabine and docetaxel at the dose and schedule used is not recommended for HCC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis