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 Journal Article
| Authors: | Motzer, R. J.; Michaelson, M. D.; Redman, B. G.; Hudes, G. R.; Wilding, G.; Figlin, R. A.; Ginsberg, M. S.; Kim, S. T.; Baum, C. M.; Deprimo, S. E.; Li, J. Z.; Bello, C. L.; Theuer, C. P.; George, D. J.; Rini, B. I. |
| Article Title: | 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 |
| 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 > 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. © 2006 by American Society of Clinical Oncology. |
| Keywords: | adult; controlled study; treatment response; aged; unclassified drug; major clinical study; clinical trial; constipation; fatigue; neutropenia; bevacizumab; sunitinib; diarrhea; drug efficacy; drug safety; drug withdrawal; hypertension; side effect; anorexia; vasculotropin receptor; quality of life; controlled clinical trial; multiple cycle treatment; phase 2 clinical trial; anemia; nausea; stomatitis; thrombocytopenia; vomiting; platelet derived growth factor receptor; vasculotropin inhibitor; kidney carcinoma; drug dose escalation; lymphocytopenia; drug mechanism; multicenter study; clinical research; dermatitis; drug blood level; drug metabolite; dyspepsia; triacylglycerol lipase blood level; kidney metastasis; su 12662; heart ejection fraction; hyperamylasemia |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 24 |
| Issue: | 1 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2006-01-01 |
| Start Page: | 16 |
| End Page: | 24 |
| Language: | English |
| DOI: | 10.1200/jco.2005.02.2574 |
| PROVIDER: | scopus |
| PUBMED: | 16330672 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 902" - "Export Date: 4 June 2012" - "CODEN: JCOND" - "Source: Scopus" |
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