摘要

BACKGROUND:Pyrexia is a frequent adverse event with combined dabrafenib and trametinib therapy (CombiDT), but little is known of its clinical associations, etiology, or appropriate management.
PATIENTS AND METHODS:All patients on the BRF133220 phase I/II trial of CombiDT treated at the standard dose (150/2) were included for assessment of pyrexia (n = 201). BRAF and MEK inhibitor-naïve patients (n = 117) were included for efficacy analyses. Pyrexia was defined as temperature ≥38°C (≥100.4(°)F) or related symptoms.
RESULTS:Fifty-nine percent of patients developed pyrexia during treatment, 24% of which had pyrexia symptoms without a recorded elevation in body temperature. Pyrexia was grade 2+ in 60% of pyrexia patients. Median time to onset of first pyrexia was 19 days, with a median duration of 9 days. Pyrexia patients had a median of two pyrexia events, but 21% had three or more events. Various pyrexia management approaches were conducted in this study. A trend was observed between dabrafenib and hydroxy-dabrafenib exposure and pyrexia. No baseline clinical characteristics predicted pyrexia, and pyrexia was not statistically significantly associated with treatment outcome.
CONCLUSIONS:Pyrexia is a frequent and recurrent toxicity with CombiDT treatment. No baseline features predict pyrexia, and it is not associated with clinical outcome. Dabrafenib and metabolite exposure may contribute to the etiology of pyrexia. The optimal secondary prophylaxis for pyrexia is best studied in a prospective trial.

译文

背景: 发热是达巴非尼和曲马替尼联合治疗 (CombiDT) 的常见不良事件,但对其临床相关性、病因或适当处理知之甚少。
治疗方法: 所有患者在 BRF133220 第一阶段/二号 CombiDT 治疗的标准剂量 (150/2) 被列入评估的发热 (n = 201)。纳入 BRAF 和 MEK 抑制剂初治患者 (n = 117) 进行疗效分析。发热定义为体温 ≥ 38 ℃ (≥ 100.4 (°) F) 或相关症状。
结果: 59% 的患者在治疗期间出现发热症状,其中 24% 的患者出现发热症状,但没有记录到体温升高。60% 的发热患者发热为 2 级。首次发热发病的中位时间为 19 天,中位持续时间为 9 天。发热患者平均有两次发热事件,但 21% 有三次或三次以上。各种发热的管理方法进行了研究。Dabrafenib 之间观察到的趋势和羟基 dabrafenib 曝光和发热。没有基线临床特征预测发热,发热与治疗结果在统计学上没有显著相关性。
结论: 发热是 CombiDT 治疗的一种常见且反复出现的毒性反应。没有基线特征预测发热,并且与临床结果无关。Dabrafenib 和代谢物暴露可能导致发热的病因。发热的最佳二级预防最好在前瞻性试验中研究。

Pyrexia

呼吸 疾病症状 疾病
概述  :  

症状概述 正常人体的体温在体温调节中枢的控制下,产热和散热处于动态平衡之中,维持人体的体温在相对恒定的范围之中,腋窝下所测的体温为36℃~37℃;口腔中舌下所测的体温为36.3℃~37.2℃;肛门内所测的体温为36.5℃~37.7℃。在生理状态下,不同的个体、不同的时间和不同的环境,人体体温会有所不同。①不同个体间的体温有差异:儿童由于代谢率较高,体温可比成年人高;老年人代谢率低,体温比成年人低。②同一个体体温在不同时间有差异:正常情况下,人体体温在早晨较低,下午较高;妇女体温在排卵期和妊娠期较

Pyrexia   /paɪ'rɛksɪə/ 

释    义   n. [临床] 发热;热病

同根词   pyretic adj. 热病的;发热的;引起热病的

               pyretic n.解热剂

例    句   Pyrexia may be directly or indirectly correlated with stroke via several mechanisms. 发热通过多种机制可直接或间接与卒中有关。

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