Mechanisms of hypertension associated with BAY 43-9006

被引:264
作者
Veronese, ML
Mosenkis, A
Flaherty, KT
Gallagher, M
Stevenson, JP
Townsend, RR
O'Dwyer, PJ
机构
[1] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Med, Philadelphia, PA 19104 USA
关键词
D O I
10.1200/JCO.2005.02.0503
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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, enclothelin 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.
引用
收藏
页码:1363 / 1369
页数:7
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