© 2007 European Society for Medical Oncology
small molecule kinasi inhibitors |
Protein kinase inhibitors in the treatment of renal cell carcinoma: sorafenib
1 Department of Medical Oncology
2 Department of Radiology, Ospedale Santa Maria della Misericordia, Perugia, Italy
* Correspondence to: Dr S. Bracarda, S.C. Medical Oncology, Ospedale Santa Maria della Misericordia, Via G. Dottori, 1, 06156 Perugia, Italy. Tel: +39-075578-4212; Fax: +39-075527-9082; E-mail: serbrac{at}unipg.it
Sorafenib is an orally available multikinase inhibitor active on vascular endothelial growth factor receptor-2 and -3, platelet-derived growth factor receptor-ß, B-RAF, C-RAF, flt3 and C-Kit. Phase I studies showed its activity on renal cell carcinoma (RCC) and other neoplasms and identified the schedule of 400 mg (two tablets) b.i.d. as better tolerated and potentially active. The original design selected for the principal phase II trial, randomization discontinuation trial, showed the particular activity profile of this drug: low objective response rates but significant increases in progression-free survival [PFS, which frequently translate in increased overall survival (OS)]. A pattern of response completely agrees with an antiangiogenic (cytostatic) agent. The potential efficacy of sorafenib was confirmed in immunotherapy-refractory advanced RCC cases by ‘TARGETs', the largest randomized double-blind study ever carried out in kidney cancer. With a doubled PFS, a trend in OS and a modest toxicity profile, mainly grade 1–2 skin toxicity and diarrhea, sorafenib has been recently approved from the Food and Drug Administration and European Agency for the Evaluation of Medicinal Products for the second-line treatment of advanced RCC. Numerous trials are ongoing to test new schedules and drug combinations, while promising results were recently achieved also in hepatocellular carcinoma. With drugs such as sorafenib, angiogenesis could become an Achilles’s heel for RCC.
Key words: angiogenesis, BAY 43-9006, protein kinase inhibitors, renal cell carcinoma, sorafenib, VEGF
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. E. Lacouture, S. Wu, C. Robert, M. B. Atkins, H. H. Kong, J. Guitart, C. Garbe, A. Hauschild, I. Puzanov, D. T. Alexandrescu, et al. Evolving Strategies for the Management of Hand-Foot Skin Reaction Associated with the Multitargeted Kinase Inhibitors Sorafenib and Sunitinib Oncologist, September 1, 2008; 13(9): 1001 - 1011. [Abstract] [Full Text] [PDF]
|
|