A dosing/cross-development study of the multikinase inhibitor sorafenib in patients with pulmonary arterial hypertension.
A dosing/cross-development study of the multikinase inhibitor sorafenib in patients with pulmonary arterial hypertension.
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DOI：
10.1038/clpt.2009.217
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发表时间：
2010-03
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
肺动脉高压（PAH）和癌症具有共同的病理生理学要素。这为交叉开发可用于改善 PAH 护理的抗癌药物提供了机会。新药在这些疾病人群中的适应需要采取结构化的方法。这项研究是一项针对多激酶/血管生成抑制剂索拉非尼的为期 16 周、Ib 期、单中心、开放标签试验。为了评估索拉非尼治疗 PAH 的安全性，患有晚期但病情稳定且接受肠外前列腺素类药物（联合或不联合口服西地那非）的患者开始以癌症患者的最低活性剂量进行治疗：每天 200 毫克。患者每周接受临床评估，每月进行功能测试，剂量逐渐增加至最终剂量 400 mg，每天两次。在 12 名患者（其中 10 名女性）中，索拉非尼 200 mg 每日两次的耐受性良好。最常见的不良事件是手脚的中度皮肤反应和脱发。因此，我们的结论是，这是用于测试索拉非尼对 PAH 患者的治疗活性的可耐受给药方案。
Pulmonary arterial hypertension (PAH) and cancer share elements of pathophysiology. This provides an opportunity for the cross-development of anticancer agents that can be used in improving PAH care. The adaptation of new drugs across these disease populations warrants a structured approach. This study was a 16-week, phase Ib, single-center, open-label trial of the multikinase/angiogenesis inhibitor sorafenib. In order to assess the safety of sorafenib in PAH, patients with advanced but stable disease on parenteral prostanoids (with or without oral sildenafil) were initiated on treatment at the lowest active dosage administered to cancer patients: 200 mg daily. Patients underwent weekly clinical evaluations and monthly functional testing and dose escalations to a final dosage of 400 mg twice daily. Among 12 patients (10 of them women), sorafenib was well tolerated at 200 mg twice daily. The most common adverse events were moderate skin reactions on the hands and feet and alopecia. Our conclusion was therefore that this is a tolerable dosing regimen for testing the therapeutic activity of sorafenib in PAH patients.
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DOI：
10.1164/rccm.200709-1369pp
发表时间：
2008-09-15
影响因子：
24.7
作者：
Rai, Pradeep R.;Cool, Carlyne D.;Voelkel, Norbert F.
通讯作者：
Voelkel, Norbert F.
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
158.5
作者：
GIAID, A;YANAGISAWA, M;STEWART, DJ
通讯作者：
STEWART, DJ
影响因子：
37.8
作者：
Klein, Martina;Schermuly, Ralph T.;Schaefer, Stefan
通讯作者：
Schaefer, Stefan
影响因子：
82.9
作者：
Kerkela, Risto;Grazette, Luanda;Force, Thomas
通讯作者：
Force, Thomas