Sorafenib and Sunitinib in the Treatment of Advanced Non-Small Cell Lung Cancer

Abstract

LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Describe the molecular mechanisms of action, safety profile, rationale for NSCLC treatment, and main current evidence in NSCLC treatment using the multikinase inhibitors sorafenib and sunitinib.2. Summarize the main clinical trials performed with sorafenib and sunitinib in the treatment of solid tumors.3. Describe the clinical trials performed with sorafenib and sunitinib in NSCLC and suggest the future clinical development of these two drugs in the treatment of NSCLC.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACT

MAPK-independent impairment of T-cell responses by the multikinase inhibitor sorafenib

“…Sorafenib, which has been already clinically tested since 2000 for the treatment of different cancers, is a multikinase inhibitor with high activity toward RAF kinases, vascular endothelial growth factor receptors, platelet-derived growth factor receptors, FLT3, and KIT (9,24). Indeed, sorafenib is very efficient in the treatment of advanced renal cell and hepatocellular carcinoma, which consequently led to its approval by the Food and Drug Administration for therapy of this malignancies (10,25).…”

“…As monotherapeutic agent, however, it failed to show any efficacy (8). However, sorafenib is inhibitory not only to RAF kinases but also to more distantly related kinases including vascular endothelial growth factor receptors 2 and 3, platelet-derived growth factor receptor, FLT3, and KIT (9). Indeed, the success of sorafenib in the treatment of renal cell carcinoma (10) is primarily attributed to inhibition of angiogenesis by blocking vascular endothelial growth factor and platelet-derived growth factor receptors (11).…”

Combined Inhibition of the VEGFR and EGFR Signaling Pathways in the Treatment of NSCLC

“…The formation and maintenance of new vasculature (i.e., angiogenesis) is closely regulated by a balance between factors that support the development of new vessels and factors opposing the development of new vessels [5,6]. In healthy individuals, angiogenesis is strictly limited to discrete and focal time periods such as development, reproduction, and wound healing [7].…”

Synergistic antitumor activity of low-dose c-Met tyrosine kinase inhibitor and sorafenib on human non-small cell lung cancer cells

“…Ongoing clinical trials are studying its activity in other types of malignancy, including NSCLC (11,12). The effects of Sorafenib have been confirmed effect in preclinical models of NSCLC (13,14). However, Sorafenib does not improve the overall survival time of patients with advanced NSCLC (15).…”