Pazopanib: a multikinase inhibitor with activity in advanced renal cell carcinoma

被引:21
作者
Bukowski, Ronald M. [1 ]
机构
[1] CCF Lerner Coll Med CWRU, Cleveland Clin, Taussig Canc Ctr, Cleveland, OH USA
关键词
pazopanib; renal cell carcinoma; tyrosine kinase inhibitors; ENDOTHELIAL GROWTH-FACTOR; PHASE-I TRIAL; INTERFERON-ALPHA; SUNITINIB;
D O I
10.1586/ERA.10.38
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Treatment options for patients with metastatic renal cell carcinoma (RCC) have changed dramatically, and a new paradigm has evolved. IFN-alpha and IL-2 were previously mainstays of therapy, but since December 2005, six new agents have been approved in the USA for the treatment of advanced RCC. Three of these new agents are multitargeted kinase inhibitors, including sunitinib, sorafenib, and recently pazopanib, two target the mTOR (temsirolimus and everolimus), and one is a humanized monoclonal antibody (bevacizumab in combination with IFN-alpha) that targets VEGF. Sunitinib has emerged as the standard of care for treatment-naive RCC patients, with the recently approved bevacizumab and IFN-a combination providing an additional option for this population. The recent approval of pazopanib, based on the results from sequential Phase II and III clinical trials demonstrating improved overall response rates and progression-free survival, provides yet another option for front-line therapy. The current article examines the pazopanib preclinical and clinical data, provides an overview of the development of this tyrosine kinase inhibitor, and provides some speculation concerning its role in RCC therapy.
引用
收藏
页码:635 / 645
页数:11
相关论文
共 30 条
[1]  
BRADY J, 2009, J CLIN ONCOL S, V15, P27
[2]   Pazopanib [J].
Bukowski, Ronald M. ;
Yasothan, Uma ;
Kirkpatrick, Peter .
NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (01) :17-18
[3]   Tumor-derived lymphangiogenic factors and lymphatic metastasis [J].
Cao, Yihai ;
Zhong, Weide .
BIOMEDICINE & PHARMACOTHERAPY, 2007, 61 (09) :534-539
[4]   Pazopanib: an antiangiogenic drug in perspective [J].
Castaneda, Carlos A. ;
Gomez, Henry L. .
FUTURE ONCOLOGY, 2009, 5 (09) :1335-1348
[5]   Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes [J].
Dalgliesh, Gillian L. ;
Furge, Kyle ;
Greenman, Chris ;
Chen, Lina ;
Bignell, Graham ;
Butler, Adam ;
Davies, Helen ;
Edkins, Sarah ;
Hardy, Claire ;
Latimer, Calli ;
Teague, Jon ;
Andrews, Jenny ;
Barthorpe, Syd ;
Beare, Dave ;
Buck, Gemma ;
Campbell, Peter J. ;
Forbes, Simon ;
Jia, Mingming ;
Jones, David ;
Knott, Henry ;
Kok, Chai Yin ;
Lau, King Wai ;
Leroy, Catherine ;
Lin, Meng-Lay ;
McBride, David J. ;
Maddison, Mark ;
Maguire, Simon ;
McLay, Kirsten ;
Menzies, Andrew ;
Mironenko, Tatiana ;
Mulderrig, Lee ;
Mudie, Laura ;
O'Meara, Sarah ;
Pleasance, Erin ;
Rajasingham, Arjunan ;
Shepherd, Rebecca ;
Smith, Raffaella ;
Stebbings, Lucy ;
Stephens, Philip ;
Tang, Gurpreet ;
Tarpey, Patrick S. ;
Turrell, Kelly ;
Dykema, Karl J. ;
Khoo, Sok Kean ;
Petillo, David ;
Wondergem, Bill ;
Anema, John ;
Kahnoski, Richard J. ;
Teh, Bin Tean ;
Stratton, Michael R. .
NATURE, 2010, 463 (7279) :360-363
[6]  
DEJONGE M, 2006, J CLIN ONCOL S, V18, P3088
[7]  
ESCUDIER B, 2009, J CLIN ONCOL, V27, P1
[8]   Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial [J].
Escudier, Bernard ;
Pluzanska, Anna ;
Koralewski, Piotr ;
Ravaud, Alain ;
Bracarda, Sergio ;
Szczylik, Cezary ;
Chevreau, Christine ;
Filipek, Marek ;
Melichar, Bohuslav ;
Bajetta, Emilio ;
Gorbunova, Vera ;
Bay, Jacques-Olivier ;
Bodrogi, Istvan ;
Jagiello-Gruszfeld, Agnieszka ;
Moore, Nicola .
LANCET, 2007, 370 (9605) :2103-2111
[9]   Phase I Trial of Bevacizumab Plus Escalated Doses of Sunitinib in Patients With Metastatic Renal Cell Carcinoma [J].
Feldman, Darren R. ;
Baum, Michael S. ;
Ginsberg, Michelle S. ;
Hassoun, Hani ;
Flombaum, Carlos D. ;
Velasco, Susanne ;
Fischer, Patricia ;
Ronnen, Ellen ;
Ishill, Nicole ;
Patil, Sujata ;
Motzer, Robert J. .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (09) :1432-1439
[10]  
FRENTZAS SN, 2009, J CLIN ONCOL S, V15, P27