Mechanisms of hypertension associated with BAY 43-9006.
OBJECTIVE
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.


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 > or = 10 mmHg in systolic BP (SBP), and 12 (60%) of 20 patients experienced an increase of > or = 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.


CONCLUSIONS
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.
Veronese
Maria Luisa
ML
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mosenkis
Ari
A
Flaherty
Keith T
KT
Gallagher
Maryann
M
Stevenson
James P
JP
Townsend
Raymond R
RR
O'Dwyer
Peter J
PJ
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000077157:Sorafenib
D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib