Efficacy And Safety Of A Phase Ii Study Of Sorafenib Plus Gemcitabine In Advanced Hepatocellular Carcinoma.

e14633 Background: Currently, the only standard systemic treatment for advanced hepatocellular carcinoma (HCC) is sorafenib monotherapy. In searching for an improved regimen of systemic treatment, we chose to use gemcitabine which has a modest activity but acceptable toxicity in advanced HCC to combine with sorafenib. Here we report the first efficacy and safety analysis of this novel combination in the treatment of advanced HCC. Methods: The study is a single arm sorafenib plus gemcitabine in patients with metastatic or unresectable HCC. Pathological diagnosis of HCC is mandatory. Treatment includes 4-week cycle of gemcitabine (1,000 mg/m2 day 1, 8, 15) to maximum of 6 cycles together with sorafenib (200 mg twice daily). Patient would continue sorafenib until disease progression or withdrawal from other reason. The primary endpoint is the progression free survival (PFS). Results: Forty five patients were eligible. Almost all patients had Child-Pugh score A (42/45, 93.3%). There were 28/45 (62.2%) patients who had hepatitis B virus associated HCC and 23/45 (51.1%) who had extrahepatic metastases. The overall response rate was 2/39 (5.1%) without complete response and the disease control rate was 30/39 (76.9%). The median PFS was 3.7 (3.5, 3.8) months with the longest time of treatment over 16 months. The median overall survival was at 12 (7.5, 16) months. Reported grade 3/4 treatment related adverse events (AE) include 33% thrombocytopenia, 15.6% neutropenia, and 15.6% hand-foot skin reaction. The study regimen was well tolerated with 4 patients discontinued from the treatment due to adverse events. There was one death during study treatment. Conclusions: The combination of sorafenib and gemcitabine in advanced HCC has a moderate clinical efficacy and encouraging long survival with acceptable toxicities comparing to th sorafenib monotherapy. Future studies in a larger randomized population are warranted.