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

DOI Web Site 被引用文献32件
  • Robert J. Motzer
    From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; Fox Chase Cancer Center, Philadelphia, PA; University of Wisconsin, Madison, WI; University of California Los Angeles, Los Angeles; Pfizer Inc, La Jolla; and University of California San Francisco, San Francisco, CA
  • M. Dror Michaelson
    From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; Fox Chase Cancer Center, Philadelphia, PA; University of Wisconsin, Madison, WI; University of California Los Angeles, Los Angeles; Pfizer Inc, La Jolla; and University of California San Francisco, San Francisco, CA
  • Bruce G. Redman
    From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; Fox Chase Cancer Center, Philadelphia, PA; University of Wisconsin, Madison, WI; University of California Los Angeles, Los Angeles; Pfizer Inc, La Jolla; and University of California San Francisco, San Francisco, CA
  • Gary R. Hudes
    From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; Fox Chase Cancer Center, Philadelphia, PA; University of Wisconsin, Madison, WI; University of California Los Angeles, Los Angeles; Pfizer Inc, La Jolla; and University of California San Francisco, San Francisco, CA
  • George Wilding
    From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; Fox Chase Cancer Center, Philadelphia, PA; University of Wisconsin, Madison, WI; University of California Los Angeles, Los Angeles; Pfizer Inc, La Jolla; and University of California San Francisco, San Francisco, CA
  • Robert A. Figlin
    From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; Fox Chase Cancer Center, Philadelphia, PA; University of Wisconsin, Madison, WI; University of California Los Angeles, Los Angeles; Pfizer Inc, La Jolla; and University of California San Francisco, San Francisco, CA
  • Michelle S. Ginsberg
    From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; Fox Chase Cancer Center, Philadelphia, PA; University of Wisconsin, Madison, WI; University of California Los Angeles, Los Angeles; Pfizer Inc, La Jolla; and University of California San Francisco, San Francisco, CA
  • Sindy T. Kim
    From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; Fox Chase Cancer Center, Philadelphia, PA; University of Wisconsin, Madison, WI; University of California Los Angeles, Los Angeles; Pfizer Inc, La Jolla; and University of California San Francisco, San Francisco, CA
  • Charles M. Baum
    From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; Fox Chase Cancer Center, Philadelphia, PA; University of Wisconsin, Madison, WI; University of California Los Angeles, Los Angeles; Pfizer Inc, La Jolla; and University of California San Francisco, San Francisco, CA
  • Samuel E. DePrimo
    From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; Fox Chase Cancer Center, Philadelphia, PA; University of Wisconsin, Madison, WI; University of California Los Angeles, Los Angeles; Pfizer Inc, La Jolla; and University of California San Francisco, San Francisco, CA
  • Jim Z. Li
    From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; Fox Chase Cancer Center, Philadelphia, PA; University of Wisconsin, Madison, WI; University of California Los Angeles, Los Angeles; Pfizer Inc, La Jolla; and University of California San Francisco, San Francisco, CA
  • Carlo L. Bello
    From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; Fox Chase Cancer Center, Philadelphia, PA; University of Wisconsin, Madison, WI; University of California Los Angeles, Los Angeles; Pfizer Inc, La Jolla; and University of California San Francisco, San Francisco, CA
  • Charles P. Theuer
    From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; Fox Chase Cancer Center, Philadelphia, PA; University of Wisconsin, Madison, WI; University of California Los Angeles, Los Angeles; Pfizer Inc, La Jolla; and University of California San Francisco, San Francisco, CA
  • Daniel J. George
    From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; Fox Chase Cancer Center, Philadelphia, PA; University of Wisconsin, Madison, WI; University of California Los Angeles, Los Angeles; Pfizer Inc, La Jolla; and University of California San Francisco, San Francisco, CA
  • Brian I. Rini
    From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Massachusetts General Hospital; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; Fox Chase Cancer Center, Philadelphia, PA; University of Wisconsin, Madison, WI; University of California Los Angeles, Los Angeles; Pfizer Inc, La Jolla; and University of California San Francisco, San Francisco, CA

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<jats:sec><jats:title>Purpose</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> 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. </jats:p></jats:sec>

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