Early development of sunitinib in hepatocellular carcinoma

Abstract

Sunitinib malate is an oral, multitargeted receptor tyrosine kinase inhibitor of VEGF receptors 1, 2 and 3; PDGF receptors α and β, and other receptor tyrosine kinases implicated in tumor growth, angiogenesis and metastasis. Hepatocellular carcinoma (HCC) is a highly vascular tumor that overexpresses several angiogenic factors; VEGF and PDGF signaling pathways play a key role in HCC. Until recently, treatment options for advanced HCC were limited and conventional therapies have met with poor response rates. Sorafenib provided proof-of-concept for molecularly targeted therapy in advanced HCC and has recently been approved for treatment. However, not all patients can tolerate sorafenib and patients may experience tumor progression; therefore, additional treatment options are warranted. Sunitinib has shown early evidence of anti-tumor activity in Phase II trials in US, European and Asian patients with locally advanced, unresectable and metastatic HCC. A Phase III trial of sunitinib in HCC is ongoing.

Keywords::

• antiangiogenesis
• clinical trials
• hepatocellular carcinoma
• multitargeted receptor tyrosine kinase inhibitor
• receptor tyrosine kinase
• sunitinib
• SUTENT^®

Financial & competing interests disclosure

A Zhu discloses his role as an advisor to Pfizer, Bayer and Genentech. E Raymond discloses his role as an advisor to Pfizer and GlaxoSmithKline. Raymond has received honoraria from Pfizer and GlaxoSmithKline and has received research funding from Pfizer and Amgen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. Editorial assistance was provided by ACUMED^® (Tytherington, UK) and was funded by Pfizer Inc.