New Treatments for Renal Cell Carcinoma: Targeted Therapies

Authors:
Philip J. Saylor Department of Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts

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 MD
and
M. Dror Michaelson Department of Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts

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 MD, PhD
Volume/Issue:
Volume 7: Issue 6
Online Publication Date:
Jun 2009
DOI:
https://doi.org/10.6004/jnccn.2009.0045
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Systemic treatment options for advanced renal cell carcinoma (RCC) have expanded considerably with the development of targeted therapies. Clear cell RCC commonly features mutation or inactivation of the von Hippel-Lindau gene and resultant overexpression of vascular endothelial growth factor (VEGF). The first drug to validate VEGF as a target in the treatment of clear cell RCC was the monoclonal antibody bevacizumab. Since then, anti-VEGF receptor therapy with multitargeted kinase inhibitors also has shown substantial efficacy. Sunitinib is now a standard first-line therapy for advanced disease and sorafenib is among the second-line treatment options. Other kinase inhibitors are in development. Mammalian target of rapamycin (mTOR) is a second validated therapeutic target as the mTOR inhibitor temsirolimus has been shown to prolong survival in first-line treatment of poor prognosis RCC of all histologies. Everolimus is an oral mTOR inhibitor and has been shown to prolong progression-free survival when used in second-line treatment. Non-clear cell and sarcomatoid RCC are both underrepresented in completed trials but are the subject of active research. Ongoing and planned studies will also evaluate the use of combinations of targeted agents, a strategy that is not advisable outside of clinical trials. Finally, postnephrectomy adjuvant treatment with targeted agents is not yet standard but is under investigation in phase III trials.

Dr. Michaelson has disclosed that he has received honoraria from Wyeth, Pfizer Inc., Abbott Laboratories, Genentech, Inc., and Novartis. Dr. Saylor has no interest, arrangement, or affiliation with the manufacturers of any products discussed in the article or their competitors.

Correspondence: Philip J. Saylor, MD, Massachusetts General Hospital, Lawrence House/POB: 2nd Floor, Boston, MA 02114. E-mail: psaylor@partners.org
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Copyright:
Copyright © 2009 by the National Comprehensive Cancer Network 2009
Page Numbers:
12
Article Category:
Research Article
Received:
04 Feb 2009
Accepted:
22 Apr 2009
Print Publication Date:
01 Jun 2009
Online Publication Date:
Jun 2009
Keywords:
Renal cell carcinoma; tyrosine kinase inhibitors; vascular endothelial growth factor; mammalian target of rapamycin; von Hippel-Lindau; hypoxia inducible factor
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