[Mechanisms of Hypertension Associated With BAY 43-9006]
>>JCO Early Release, published online ahead of print Jan 30 2006
Journal of Clinical Oncology, 10.1200/JCO.2005.02.0503
Received March 17, 2005
Accepted November 1, 2005
Mechanisms of Hypertension Associated With BAY 43-9006
Maria Luisa Veronese , Ari Mosenkis , Keith T. Flaherty , Maryann Gallagher , James P. Stevenson , Raymond R. Townsend , and Peter J. O'Dwyer *
From the Abramson Cancer Center at the University of Pennsylvania; and Department of Medicine, University of Pennsylvania, Philadelphia, PA.
* To whom correspondence should be addressed. E-mail: peter.odwyer@uphs.upenn.edu
Purpose: BAY 43-9006 (sorafenib) is an inhibitor of Raf kinase, the vascular endothelial growth factor (VEGF) receptor-2, and angiogenesis in tumor xenografts. The current study investigated the incidence, severity, and mechanism of blood pressure (BP) elevation in patients treated with BAY 43-9006.
Patients and Methods: Twenty patients received BAY 43-9006 400 mg orally twice daily. BP and heart rate were measured at baseline and then every 3 weeks for 18 weeks. VEGF, catecholamines, endothelin I, urotensin II, renin, and aldosterone were measured at baseline and after 3 weeks of therapy. We assessed vascular stiffness at baseline, after 3 to 6 weeks of therapy, and again after 9 to 10 months of therapy.
Results: Fifteen (75%) of 20 patients experienced an increase of 10 mmHg in systolic BP (SBP), and 12 (60%) of 20 patients experienced an increase of 20 mmHg in SBP compared with their baseline value, with a mean change of 20.6 mmHg (P < .0001) after 3 weeks of therapy. There were no statistically significant changes in humoral factors, although there was a statistically significant inverse relationship between decreases in catecholamines and increases in SBP, suggesting a secondary response to BP elevation. Measures of vascular stiffness increased significantly during the period of observation.
Conclusion: Treatment with BAY 43-9006 is associated with a significant and sustained increase in BP. The lack of significant change in circulating factors suggests that these humoral factors had little role in the increase in BP.<<
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