Systemic chemotherapy of hepatocellular carcinoma--Korean experience

Surgical resection, transarterial chemoembolization, percutaneous ethanol injection therapy, radiofrequency ablation, and orthotopic liver transplantation are generally accepted treatment modalities in hepatocellular carcinoma, but there has been no standard therapy for patients at the advanced stage. Several combinations of various cytotoxic agents have been tried in Korea, but definite conclusions could not be drawn because of small sample size, heterogenous populations among studies, several biases, and lack of a control arm. There has been no evidence so far that either of the combination chemotherapies is superior to single-agent chemotherapy or systemic chemotherapy has any clinical benefit in terms of patient survival. Recent advances in molecular biology have identified several important signal transduction pathways during hepatocarcinogenesis, which enables us to control the key elements of these signaling pathways. Accordingly, several new 'targeted agents' have been developed and are under clinical trial at present. In contrast to previous cytotoxic agents, most targeted agents do not induce regression of tumors but stabilize disease progression. Sorafenib is the first drug proven to prolong survival in advanced stage patients. However, the survival benefit is still not satisfactory; therefore, future trials should be conducted regarding the combination of sorafenib with other preexisting treatment modalities or new targeted agents.