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Development of Sunitinib in Hepatocellular Carcinoma: Rationale, Early Clinical Experience, and Correlative Studies

Zhu, Andrew X. MD, PhD; Duda, Dan G. MD, PhD; Sahani, Dushyant V. MD; Jain, Rakesh K. PhD

doi: 10.1097/PPO.0b013e3181af5e35
Practice of Oncology: Recent Advances

The approval of a multitargeted receptor tyrosine kinase inhibitor, sorafenib, with activity against vascular endothelial growth factor receptor-2 and -3, Raf-1 and B-Raf, platelet-derived growth factor receptor-α and -β, and other kinases, has ushered in the era of molecular targeted agents in advanced hepatocellular carcinoma (HCC). Sunitinib malate is an oral, multitargeted inhibitor of vascular endothelial growth factor receptor-1, -2, and -3, platelet-derived growth factor receptor-α and -β, and other kinases implicated in tumor growth, angiogenesis, and metastasis. Sunitinib has been approved in metastatic renal cell carcinoma and gastrointestinal stromal tumor and is undergoing active clinical development in HCC. Early evidence of antitumor activity and a promising safety profile for this agent have emerged from single arm phase II trials in United States, European, and Asian patients with advanced HCC. Correlative studies of imaging and circulating biomarkers have provided insights into the potential mechanism of action of sunitinib. Additional phase II studies using either single agent or in combination with chemotherapeutic agents are ongoing, and a phase III trial comparing sunitinib and sorafenib in advanced HCC is actively accruing patients. Here, we review the current progress and future directions for the development of sunitinib in advanced HCC.

From the Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA.

Andrew X. Zhu discloses his role as an advisor to Bayer and Genentech. Dr. Rakesh K. Jain discloses his role as consultant/advisor to AstraZeneca, Dyax, Millenium and SynDevRx, receives research support from AstraZeneca and Dyax, and has received honoraria for lectures from Roche and Pfizer.

Reprints: Andrew X. Zhu, MD, PhD, Tucker Gosnell Center for Gastrointestinal Cancers, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA. E-mail: azhu@partners.org.

© 2009 Lippincott Williams & Wilkins, Inc.