Management of advanced hepatocellular carcinoma in the era of targeted therapy.
Systemic chemotherapy has had a disappointing track record in the management of advanced hepatocellular carcinoma (HCC). Single-agent doxorubicin produces a response rate of 10-15%, but without any survival benefit, and combination chemotherapy has also yielded unimpressive results. With recent advances in the knowledge of hepato-carcinogenesis, there has been encouraging development in the systemic therapy of advanced HCC patients, and particularly in the targeted therapy of advanced HCC. Among the newly identified targets, exciting results have been shown in targeting the anti-angiogenic pathway and the Raf/mitogen-activated protein kinase pathways. Bevacizumab, both as a single agent and in combination with other agents, has shown initial encouraging activity in treating advanced HCC. More recently, single-agent sorafenib, a putative multitargeted kinase inhibitor, has shown to prolong the overall survival of patients with advanced HCC in the pivotal phase III Sorafenib HCC Assessment Randomized Protocol (SHARP) and Oriental study. Currently, sorafenib is the only approved targeted therapy for patients with advanced HCC. In addition, however, promising early results have been reported for other molecular-targeted drugs including erlotinib and sunitinib. Future progress seems likely to depend on using controlled clinical trials to optimize synergistic combination treatments.
Yau
Thomas
T
University Department of Medicine, Queen Mary Hospital, Hong Kong, Hong Kong. the@netvigator.com
Chan
Pierre
P
Epstein
Richard
R
Poon
Ronnie Tung Ping
RT
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D016503:Drug Delivery Systems / Q000379:methods*; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*; D000077157:Sorafenib
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000068258:Bevacizumab; D004815:Epidermal Growth Factor; D000077157:Sorafenib; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases