Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma.

Published

Journal Article

PURPOSE: Renal cell carcinoma (RCC) is characterized by loss of von Hippel Lindau tumor suppressor gene activity, resulting in high expression of pro-angiogenic growth factors: vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). SU11248 (sunitinib malate), a small molecule inhibitor with high binding affinity for VEGF and PDGF receptors, was tested for clinical activity in patients with metastatic RCC. PATIENTS AND METHODS: Patients with metastatic RCC and progression on first-line cytokine therapy were enrolled onto a multicenter phase II trial. SU11248 monotherapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off. Overall response rate was the primary end point, and time to progression and safety were secondary end points. Results Twenty-five (40%) of 63 patients treated with SU11248 achieved partial responses; 17 additional patients (27%) demonstrated stable disease lasting > or = 3 months. Median time to progression in the 63 patients was 8.7 months. Dosing was generally tolerated with manageable toxicities. CONCLUSION: SU11248, a multitargeted receptor tyrosine kinase inhibitor of VEGF and PDGF receptors, demonstrates antitumor activity in metastatic RCC as second-line therapy, a setting where no effective systemic therapy is presently recognized. The genetics of RCC and these promising clinical results support the hypothesis that VEGF and PDGF receptor-mediated signaling is an effective therapeutic target in RCC.

Full Text

Duke Authors

Cited Authors

  • Motzer, RJ; Michaelson, MD; Redman, BG; Hudes, GR; Wilding, G; Figlin, RA; Ginsberg, MS; Kim, ST; Baum, CM; DePrimo, SE; Li, JZ; Bello, CL; Theuer, CP; George, DJ; Rini, BI

Published Date

  • January 1, 2006

Published In

Volume / Issue

  • 24 / 1

Start / End Page

  • 16 - 24

PubMed ID

  • 16330672

Pubmed Central ID

  • 16330672

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Digital Object Identifier (DOI)

  • 10.1200/JCO.2005.02.2574

Language

  • eng

Conference Location

  • United States