Efficacy and safety of sorafenib-gemcitabine combination therapy in advanced hepatocellular carcinoma: an open-label Phase II feasibility study

ABSTRACT

Sorafenib is considered a standard of care in advanced hepatocellular carcinoma [HCC]. Its combination with gemcitabine, a pyrimidine analogue with limited friendly hepatic profile may prove beneficial in advanced HCC. The primary objective was to evaluate the efficacy and safety of a sorafenib and gemcitabine combination in patients with advanced HCC. This was a non-randomized, open-label, single-arm, multi-centric Phase II study conducted in Pakistan where 30 treatment-naive patients aged between 26 and 73 years with Child-Pugh score A or B were treated with sorafenib [400 mg oral] twice daily for 16 weeks along with gemcitabine [1000 mg/m[2] intravenous] administered on day 1 and day 8 of a four-week cycle for 16 weeks. Of the 18 patients [60%] who completed all four cycles of treatment, eight patients had stable disease, two had partial response, and eight had progressive disease. There was no complete response. The most common [>/= 10% patients] treatment-emergent adverse events were gemcitabine-related thrombocytopenia [40%] followed by sorafenib-related hand-foot skin reaction and anorexia [33% each]. The efficacy of sorafenib gemcitabine combination therapy is similar to the sorafenib alone treatment. However, frequent dose adjustments due to gemcitabine-related toxicities, delays, and corrective treatments make this combination therapy unsafe in the treatment of advanced HCC.