Originally published as JCO Early Release 10.1200/JCO.2005.02.0503 on January 30 2006

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Mechanisms of Hypertension Associated With BAY 43-9006

Maria Luisa Veronese, Ari Mosenkis, Keith T. Flaherty, Maryann Gallagher, James P. Stevenson, Raymond R. Townsend, Peter J. O'Dwyer

From the Abramson Cancer Center at the University of Pennsylvania; and Department of Medicine, University of Pennsylvania, Philadelphia, PA

Address reprint requests to Peter J. O'Dwyer, MD, Abramson Cancer Center, University of Pennsylvania, 51 N 39th St, MAB-103, Philadelphia, PA 19104; e-mail: peter.odwyer{at}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.

Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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