Pexidartinib安慰剂高级tenosynovial巨细胞瘤(活跃):随机三期试验。
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利用WD, Gelderblom H, Palmerini E,德赛J,鲍尔年代,凄凉的司法院,阿尔金德T, Ganjoo K, Martin-Broto J, Ryan CW托马斯•DM Peterfy C,希利JH, van de Sande M, Gelhorn霍奇金淋巴瘤,•舒斯特de,王Q,青年志愿,许HH,林PS, Tong-Starksen年代,Stacchiotti年代,瓦格纳AJ
Pexidartinib安慰剂高级tenosynovial巨细胞瘤(活跃):随机三期试验。
柳叶刀》。2019年6月19日。pii: s0140 - 6736 (19) 30764 - 0。doi: 10.1016 / s0140 - 6736 (19) 30764 - 0。
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31229240 (在PubMed]
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背景:Tenosynovial巨细胞瘤(TGCT),一种罕见的,本地侵略性的肿瘤,过表达集落刺激因子1 (CSF1)。手术是标准没有批准系统性治疗。我们旨在评估pexidartinib CSF1受体抑制剂,患者TGCT给他们提供一个可行的全身治疗的选择,特别是在情况下不适合手术切除。方法:这个阶段3随机试验两部分。第一部分是一个双盲研究中,患者症状,先进TGCT来说,手术是不推荐被随机分配通过一个集成的网络反应系统(1:1)pexidartinib或安慰剂组。个人pexidartinib组收到的负荷剂量1000毫克每天pexidartinib口头(400毫克的早晨;晚上600毫克)前2周,紧随其后的是每天800毫克(400毫克,一天两次),22周。第二部分是一个开放研究pexidartinib的病人。主要终点,评估在所有意向处理病人,在25周总体响应,并集中审议RECIST, 1.1版。安全分析所有患者接受至少一个剂量的药物。 This study is registered with ClinicalTrials.gov, number NCT02371369. FINDINGS: Between May 11, 2015, and Sept 30, 2016, of 174 patients assessed for eligibility, 120 patients were randomly assigned to, and received, pexidartinib (n=61) or placebo (n=59). There were 11 dropouts in the placebo group and nine in the pexidartinib group. Emergence of mixed or cholestatic hepatotoxicity caused the data monitoring committee to stop enrolment six patients short of target. The proportion of patients who achieved overall response was higher for pexidartinib than placebo at week 25 by RECIST (24 [39%] of 61 vs none of 59; absolute difference 39% [95% CI 27-53]; p<0.0001). Serious adverse events occurred in eight (13%) of 61 patients in the pexidartinib group and one (2%) of 59 patients in the placebo group. Hair colour changes (67%), fatigue (54%), aspartate aminotransferase increase (39%), nausea (38%), alanine aminotransferase increase (28%), and dysgeusia (25%) were the most frequent pexidartinib-associated adverse events. Three patients given pexidartinib had aminotransferase elevations three or more times the upper limit of normal with total bilirubin and alkaline phosphatase two or more times the upper limit of normal indicative of mixed or cholestatic hepatotoxicity, one lasting 7 months and confirmed by biopsy. INTERPRETATION: Pexidartinib is the first systemic therapy to show a robust tumour response in TGCT with improved patient symptoms and functional outcomes; mixed or cholestatic hepatotoxicity is an identified risk. Pexidartinib could be considered as a potential treatment for TGCT associated with severe morbidity or functional limitations in cases not amenable to improvement with surgery. FUNDING: Daiichi Sankyo.
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在您的软件的交互Pexidartinib 丙戊酸 丙戊酸可能会增加Pexidartinib的肝毒素的活动。 Pexidartinib Tipranavir Tipranavir可能会增加Pexidartinib的肝毒素的活动。 Pexidartinib 酮康唑 酮康唑可能会增加Pexidartinib的肝毒素的活动。 Pexidartinib Idelalisib Idelalisib可能会增加Pexidartinib的肝毒素的活动。 Pexidartinib 利福平 利福平可能会增加Pexidartinib的肝毒素的活动。 Pexidartinib 应用波生坦 应用波生坦可能会增加Pexidartinib的肝毒素的活动。 Pexidartinib 甲氨蝶呤 甲氨蝶呤可能会增加Pexidartinib的肝毒素的活动。 Pexidartinib 多烯紫杉醇 多西他赛可能会增加Pexidartinib的肝毒素的活动。 Pexidartinib Givosiran Givosiran可能会增加Pexidartinib的肝毒素的活动。 Pexidartinib Onasemnogene abeparvovec Onasemnogene abeparvovec可能会增加Pexidartinib的肝毒素的活动。
