Pazopanib: A novel multitargeted tyrosine kinase inhibitor

被引:162
作者
Sonpavde G. [1 ]
Hutson T.E. [1 ]
机构
[1] Texas Oncology P.A., Baylor Sammons Cancer Center, Dallas, TX 75246
关键词
Vascular Endothelial Growth Factor; Renal Cell Carcinoma; Sorafenib; Lapatinib; Synovial Sarcoma;
D O I
10.1007/s11912-007-0007-2
中图分类号
学科分类号
摘要
Pazopanib (GW786034) is a second-generation multitargeted tyrosine kinase inhibitor against vascular endothelial growth factor receptor-1, -2, and -3, platelet-derived growth factor receptor-α, platelet-derived growth factor receptor-β and c-kit. Preclinical evaluation has revealed excellent antiangiogenic and antitumor activity, and synergism was observed in combination with chemotherapeutic drugs. Significant antitumor activity was found in animal models of a variety of tumors, accompanied by desirable pharmacokinetics and oral bioavailability. Phase I clinical trials have revealed manageable toxicities and desirable pharmacokinetics as well as activity in renal cancer and several other tumors. Ongoing trials are further evaluating pazopanib in a variety of malignancies. Copyright © 2007 by Current Medicine Group LLC.
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页码:115 / 119
页数:4
相关论文
共 25 条
[21]  
Podar K., Tonon G., Abtahi D., Et al., In vitro and in vivo activity of the VEGF receptor inhibitor PAZOPANIB (GW786034) in Multiple myeloma: Therapeutic implications, Proc Amer Assoc Cancer Res, 47, (2006)
[22]  
Suttle A.B., Hurwitz H., Dowlati A., Et al., Pharmacokinetics (PK) and tolerability of GW786034, a VEGFR tyrosine kinase inhibitor, after daily oral administration to patients with solid tumors, J Clin Oncol Proc ASCO, 22, 14 S, (2004)
[23]  
Hurwitz H., Dowlati A., Savage S., Et al., Safety, tolerability and pharmacokinetics of oral administration of GW786034 in pts with solid tumors, J Clin Oncol, 23, 16 S, (2005)
[24]  
Hutson T.E., Bukowski R.M., A phase II study of GW786034 using a randomized discontinuation design in patients with locally recurrent or metastatic clear-cell renal cell carcinoma, Clin Genitourin Cancer, 4, pp. 296-298, (2006)
[25]  
Rini B.I., Small E.J., Biology and clinical development of vascular endothelial growth factor-targeted therapy in renal cell carcinoma, J Clin Oncol, 23, pp. 1028-1043, (2005)