Department of Medical Oncology, Hôpital Saint-André, University Hospital, Bordeaux, France.
Université Bordeaux 2 Victor Segalen, Clinical Investigational Center (CIC) INSERM 005, Bordeaux, France; Pfizer Inc., Global Research and Development, New York, New York, USA.
Targeted agents such as sunitinib, an oral, multitargeted receptor tyrosine kinase inhibitor, have greatly improved the prognosis for patients with metastatic renal cell carcinoma (mRCC). In this review we analyse data from sunitinib preclinical and clinical studies in detail and consider the key implications for the effective use of sunitinib in clinical practice. Sunitinib has shown efficacy and acceptable tolerability in patients with mRCC in phase II and III clinical studies. In a pivotal phase III study in treatment-naïve patients with mRCC, median progression-free survival for sunitinib-treated patients was double of that with interferon-α (P< 0.001). Median overall survival was 26.4 versus 21.8 months, respectively (P=0.0510). In preclinical and phase I/II studies, sunitinib inhibits tyrosine kinase inhibitors in a dose-dependent manner, suggesting a correlation between increasing exposure and greater response. A pharmacokinetics/pharmacodynamics meta-analysis investigating the relationship between clinical end points and sunitinib exposure showed that increased sunitinib exposure was associated with a greater probability of objective response, longer time to tumour progression and overall survival, as well as some increased risk of specific adverse events. It is important to consider the relationship between exposure and response to maximize clinical benefit from sunitinib treatment.
Written by:
Ravaud A, Bello CL. Are you the author?
Reference: Anticancer Drugs. 2011 Mar 9. Epub ahead of print.
PubMed Abstract
PMID: 21394020
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