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首页> 外文期刊>Clinical Pharmacology and Therapeutics >Sorafenib Dose Escalation Is Not Uniformly Associated With Blood Pressure Elevations in Normotensive Patients With Advanced Malignancies
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Sorafenib Dose Escalation Is Not Uniformly Associated With Blood Pressure Elevations in Normotensive Patients With Advanced Malignancies

机译：血压升高与晚期恶性肿瘤的血压升高患者索拉非尼剂量的升高并不一致

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摘要

Hypertension after treatment with vascular endothelial growth factor (VEGF) receptor inhibitors is associated with superior treatment outcomes for advanced cancer patients. To determine whether increased sorafenib doses cause incremental increases in blood pressure (BP), we measured 12-h ambulatory BP in 41 normotensive advanced solid tumor patients in a randomized dose-escalation study. After 7 days' treatment (400 mg b.i.d.), mean diastolic BP (DBP) increased in both study groups. After dose escalation, group A (400 mg t.i.d.) had marginally significant further increase in 12-h mean DBP (P = 0.053), but group B (600 mg b.i.d.) did not achieve statistically significant increases (P = 0.25). Within groups, individuals varied in BP response to sorafenib dose escalation, but these differences did not correlate with changes in steady-state plasma sorafenib concentrations. These findings in normotensive patients suggest BP is a complex pharmacodynamic biomarker of VEGF inhibition. Patients have intrinsic differences in sensitivity to sorafenib's BP-elevating effects.
机译：使用血管内皮生长因子（VEGF）受体抑制剂治疗后的高血压与晚期癌症患者的优异治疗效果相关。为了确定索拉非尼剂量的增加是否引起血压（BP）的增加，我们在一项随机剂量递增研究中对41名血压正常的晚期实体瘤患者进行了12小时动态血压测量。治疗7天（400 mg b.i.d.）后，两个研究组的平均舒张压BP（DBP）均升高。剂量增加后，A组（400 mg t.i.d.）在12小时平均DBP（P = 0.053）方面有轻微的显着进一步增加，但B组（600 mg b.i.d.）没有达到统计学上的显着增加（P = 0.25）。在各组中，个体对索拉非尼剂量递增的血压反应各不相同，但这些差异与稳态血浆索拉非尼浓度的变化无关。在血压正常患者中的这些发现表明，BP是VEGF抑制的复杂药效生物标志物。患者对索拉非尼升高血压的敏感性存在内在差异。

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