Development of sorafenib and other molecularly targeted agents in hepatocellular carcinoma.
It is well appreciated that hepatocellular carcinoma (HCC) represents one of the most challenging malignancies of worldwide importance. In fact, HCC is the fifth most common cancer and the third most common cause of cancer-related death globally. The incidence rates for HCC in the U.S. and Western Europe have been rising. Unresectable or metastatic HCC carries a poor prognosis, and systemic therapy with cytotoxic agents provides marginal benefit. Because of the poor track record of systemic therapy in HCC, there has been a sense of nihilism for this disease in the oncology community for decades. However, with the arrival of newly developed, molecularly targeted agents and the success of some of these agents in other traditionally challenging cancers, such as renal cell carcinoma, there has been renewed interest in developing novel systemic therapy in HCC. At the recent Annual Meeting of the American Society of Clinical Oncology, results of a phase 3, randomized, placebo-controlled trial were presented in which sorafenib demonstrated improved survival in patients with advanced HCC. This landmark study represents the first agent that has demonstrated an improved overall survival benefit in this disease and sets the new standard for first-line treatment of advanced HCC. For this review, the author concisely summarized the current status of molecularly targeted agents that are under clinical development in advanced HCC.
Tucker Gosnell Center for Gastrointestinal Cancers, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts 02114, USA. azhu@partners.org
Andrew X
AX
Zhu
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use*; D000068258:Bevacizumab; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D000077157:Sorafenib; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000068258:Bevacizumab; D000077157:Sorafenib; D066246:ErbB Receptors; D040262:Receptors, Vascular Endothelial Growth Factor; C500926:cediranib; D000077210:Sunitinib