Systemic treatment in hepatocellular carcinoma; 'A small step for man...'.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality worldwide. In localised disease, orthotopic liver transplantation, surgical resection or local ablations are the mainstay of treatment. In unresectable or metastatic HCC, systemic therapy has unfortunately yielded disappointing results and therefore until recently was generally considered to be ineffective. Most patients with HCC have an underlying liver disease and many drugs may exacerbate the underlying liver disease. Recently, two randomised phase II trials with sorafenib in patients with advanced or metastatic HCC have shown a significant increase in progression free and overall survival of approximately two months, which is an absolute novum for this disease. Sorafenib is therefore now considered a viable treatment option in patients with unresectable or metastatic HCC, a good performance status and Child-Pugh A liver cirrhosis. Despite this very promising result, of major concern is the treatment-related toxicity as observed in these and other trials by sorafenib treatment. However, the important first significant survival benefit by systemic treatment has generated hope for the development of new treatment strategies which will be more efficacious, have favourable toxicity profiles and will further extend survival of this still highly lethal disease.