Dexamethasone to prevent everolimus-induced stomatitis (Alliance MIST Trial: A221701)

IF 3 3区 医学 Q2 ONCOLOGY Seminars in oncology Pub Date : 2023-02-01 DOI:10.1053/j.seminoncol.2023.01.001
Kathryn J. Ruddy , David Zahrieh , Jun He , Blake Waechter , Julianne L. Holleran , Lionel D. Lewis , Selina Chow , Jan Beumer , Matthias Weiss , Nikolaos Trikalinos , Bryan Faller , Maryam Lustberg , Hope S. Rugo , Charles Loprinzi
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Abstract

mTOR inhibitors such as everolimus may cause oral stomatitis, often a dose-limiting toxicity. Prior clinical research has suggested that a dexamethasone mouth rinse might help prevent and/or treat this. Alliance A221701 was a randomized phase III trial of patients initiating 10 mg daily oral everolimus that compared dexamethasone mouthwash taken preventively (initial dexamethasone group) versus therapeutically (initial placebo group) to assess two coprimary endpoints: the incidence of mTOR inhibitor-associated stomatitis (mIAS), and the area under the curve (AUC) of mIAS-associated pain over an 8-week treatment period. A Fisher's exact test was used to compare the incidences while a Wilcoxon rank-sum test was used to compare the AUCs. In addition, we performed an exploratory analysis of the association of everolimus trough concentrations and toxicity using a Mann-Whitney U test. Due to slow accrual, this study closed after 39 patients were randomized (19 to upfront placebo and 20 to upfront dexamethasone). There were no significant differences between groups seen in either of the coprimary endpoints; furthermore, we found no association between whole blood everolimus trough concentrations and toxicity. Although limited by poor enrollment, the results of this study do not suggest that prophylactic dexamethasone mouthwash is superior to therapeutic dexamethasone mouthwash (initiated at the first sign of mouth pain) for reducing the incidence or severity of mIAS from everolimus.

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地塞米松预防依维莫司诱导的口腔炎(Alliance MIST试验:A221701)
mTOR抑制剂如依维莫司可能引起口腔口炎,通常是剂量限制性毒性。先前的临床研究表明,地塞米松漱口液可能有助于预防和/或治疗这种情况。Alliance A221701是一项针对开始每天口服10 mg依维莫司的患者的随机III期试验,该试验比较了预防性(初始地塞米松组)和治疗性(初始安慰剂组)使用的地塞米松漱口水,以及在8周治疗期内mIAS相关疼痛的曲线下面积(AUC)。Fisher精确检验用于比较发生率,而Wilcoxon秩和检验用于比较AUC。此外,我们使用Mann-Whitney U检验对依维莫司谷浓度和毒性的相关性进行了探索性分析。由于积累缓慢,这项研究在39名患者被随机分组后结束(19名患者接受安慰剂治疗,20名患者接受地塞米松治疗)。两组之间在任一共同主要终点方面均无显著差异;此外,我们发现全血依维莫司谷浓度与毒性之间没有关联。尽管受入选率低的限制,但本研究的结果并不表明,预防性地塞米松漱口水在降低依维莫司引起的mIAS的发生率或严重程度方面优于治疗性地塞米松漱漱口水(在出现口腔疼痛的第一个迹象时开始)。
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来源期刊
Seminars in oncology
Seminars in oncology 医学-肿瘤学
CiteScore
6.60
自引率
0.00%
发文量
58
审稿时长
104 days
期刊介绍: Seminars in Oncology brings you current, authoritative, and practical reviews of developments in the etiology, diagnosis and management of cancer. Each issue examines topics of clinical importance, with an emphasis on providing both the basic knowledge needed to better understand a topic as well as evidence-based opinions from leaders in the field. Seminars in Oncology also seeks to be a venue for sharing a diversity of opinions including those that might be considered "outside the box". We welcome a healthy and respectful exchange of opinions and urge you to approach us with your insights as well as suggestions of topics that you deem worthy of coverage. By helping the reader understand the basic biology and the therapy of cancer as they learn the nuances from experts, all in a journal that encourages the exchange of ideas we aim to help move the treatment of cancer forward.
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