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. Academic Article uri icon

Overview

abstract

  • 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.

authors

  • Motzer, Robert John
  • Michaelson, M Dror
  • Redman, Bruce G
  • Hudes, Gary R
  • Wilding, George
  • Figlin, Robert A
  • Ginsberg, Michelle
  • Kim, Sindy T
  • Baum, Charles M
  • DePrimo, Samuel E
  • Li, Jim Z
  • Bello, Carlo L
  • Theuer, Charles P
  • George, Daniel J
  • Rini, Brian I

publication date

  • December 5, 2005

Research

keywords

  • Antineoplastic Agents
  • Carcinoma, Renal Cell
  • Indoles
  • Kidney Neoplasms
  • Pyrroles
  • Receptors, Platelet-Derived Growth Factor
  • Receptors, Vascular Endothelial Growth Factor

Identity

Scopus Document Identifier

  • 33644833910

Digital Object Identifier (DOI)

  • 10.1200/JCO.2005.02.2574

PubMed ID

  • 16330672

Additional Document Info

volume

  • 24

issue

  • 1