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
作者： Robert J. Motzer , M. Dror Michaelson , Bruce G. Redman , Gary R. Hudes , George Wilding
关键词:
摘要: Purpose Renal cell carcinoma (RCC) is characterized by loss of von Hippel Lindau tumor suppressor gene activity, resulting in high expression pro-angiogenic growth factors: vascular endothelial factor (VEGF) and platelet-derived (PDGF). SU11248 (sunitinib malate), a small molecule inhibitor with binding affinity for VEGF PDGF receptors, was tested clinical activity patients metastatic RCC. Patients Methods RCC progression on first-line cytokine therapy were enrolled onto multicenter phase II trial. monotherapy administered repeated 6-week cycles daily oral 4 weeks, followed 2 weeks off. Overall response rate the primary end point, time to safety secondary points. Results Twenty-five (40%) 63 treated achieved partial responses; 17 additional (27%) demonstrated stable disease lasting ≥ 3 months. Median 6...
jco.org参考文章(42)
Farkas Sükösd, Tamas Beothe, Naoto Kuroda, Gyula Kovacs, Amrit Pal Kaur, Deletion of Chromosome 3p14.2-p25 Involving the VHL and FHIT Genes in Conventional Renal Cell Carcinoma Cancer Research. ,vol. 63, pp. 455- 457 ,(2003)
J. A Johnson, S. J Coons, Comparison of the EQ-5D and SF-12 in an adult US sample Quality of Life Research. ,vol. 7, pp. 155- 166 ,(1998) , 10.1023/A:1008809610703
Keiichi Kondo, Masahiro Yao, Minoru Yoshida, Takeshi Kishida, Taro Shuin, Takeshi Miura, Masatoshi Moriyama, Kazuki Kobayashi, Naoki Sakai, Shigeki Kaneko, Satoshi Kawakami, Masaya Baba, Noboru Nakaigawa, Yoji Nagashima, Yukio Nakatani, Masahiko Hosaka, Comprehensive mutational analysis of the VHL gene in sporadic renal cell carcinoma: relationship to clinicopathological parameters. Genes, Chromosomes and Cancer. ,vol. 34, pp. 58- 68 ,(2002) , 10.1002/GCC.10054
Othon Iliopoulos, Adam Kibel, Steven Gray, William G. Kaelin, Tumour suppression by the human von Hippel-Lindau gene product. Nature Medicine. ,vol. 1, pp. 822- 826 ,(1995) , 10.1038/NM0895-822
William Kim, William G Kaelin, The von Hippel-Lindau tumor suppressor protein: new insights into oxygen sensing and cancer. Current Opinion in Genetics & Development. ,vol. 13, pp. 55- 60 ,(2003) , 10.1016/S0959-437X(02)00010-2
J.R. Gnarra, K. Tory, Y. Weng, L. Schmidt, M.H. Wei, H. Li, F. Latif, S. Liu, F. Chen, F.-M. Duh, I. Lubensky, D.R. Duan, C. Florence, R. Pozzatti, M. M. Walther, N.H. Bander, H.B. Grossman, H. Brauch, S. Pomer, J.D. Brooks, W.B. Isaacs, M.I. Lerman, B. Zbar, W.M. Linehan, Mutations of the VHL tumour suppressor gene in renal carcinoma Nature Genetics. ,vol. 7, pp. 85- 90 ,(1994) , 10.1038/NG0594-85
Christopher D.M. Fletcher, Heikki Joensuu, George D. Demetri, Margaret von Mehren, Charles D. Blanke, Annick D. Van den Abbeele, Burton Eisenberg, Peter J. Roberts, Michael C. Heinrich, David A. Tuveson, Samuel Singer, Milos Janicek, Jonathan A. Fletcher, Stuart G. Silverman, Sandra L. Silberman, Renaud Capdeville, Beate Kiese, Bin Peng, Sasa Dimitrijevic, Brian J. Druker, Christopher Corless, Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. The New England Journal of Medicine. ,vol. 347, pp. 472- 480 ,(2002) , 10.1056/NEJMOA020461
Marc Tjwa, Aernout Luttun, Monica Autiero, Peter Carmeliet, VEGF and PlGF: two pleiotropic growth factors with distinct roles in development and homeostasis. Cell and Tissue Research. ,vol. 314, pp. 5- 14 ,(2003) , 10.1007/S00441-003-0776-3
Richard Simon, Optimal two-stage designs for phase II clinical trials. Controlled Clinical Trials. ,vol. 10, pp. 1- 10 ,(1989) , 10.1016/0197-2456(89)90015-9
Daniel J. George, William G. Kaelin, The von Hippel–Lindau Protein, Vascular Endothelial Growth Factor, and Kidney Cancer The New England Journal of Medicine. ,vol. 349, pp. 419- 421 ,(2003) , 10.1056/NEJMP030061