Novel systemic therapy options for hepatocellular carcinoma

Hepatocellular carcinoma, a common malignancy globally, has been increasing in incidence in the United States, mostly due to the rising incidence of Hepatitis C viral (HCV) infection. The prognosis of patients with this cancer has been poor and even tumor resection has rarely been curative. However, orthotopic liver transplantation (OLT) has been associated with long-term survival benefit and cures, provided rigorous patient-selection criteria were adhered to. Liver cirrhosis is the most common precursor for HCC, and attempts have been made to prevent the progression from liver cirrhosis to HCC. Post resection adjuvant therapies have included interferon, polyprenoic acid, and adoptive immunotherapy. Finding effective systemic treatments for non-resectable HCC has been challenging and quite frustrating. The presence of liver cirrhosis and the associated volume expansion, electrolyte imbalances, decreased liver synthetic and metabolic reserve, and portal hypertension has made the design of systemic therapy for HCC a major challenge. Additionally staging of HCC using the Tumor Node Metastases (TNM) system, but ignoring the underlying liver disease made it extremely difficult to compare results of different trials. However by and large it would seem, that the more aggressive chemotherapy agents and combinations were associated with median survival times of 3-5 months. Considering the vascular nature of HCC it may be reasonable to combine tolerable chemotherapy with newly released agents with angiogenesis inhibiting properties. Thus, systemic therapy of HCC is a work in progress that calls for additional trials of tolerable newer agents and combinations.