Ruddy Kathryn J, Zahrieh David, He Jun, Waechter Blake, Holleran Julianne L, Lewis Lionel D, Chow Selina, Beumer Jan, Weiss Matthias, Trikalinos Nikolaos, Faller Bryan, Lustberg Maryam, Rugo Hope S, Loprinzi Charles
Mayo Clinic, Rochester, MN.
Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN.
Semin Oncol. 2023 Feb-Apr;50(1-2):7-10. doi: 10.1053/j.seminoncol.2023.01.001. Epub 2023 Jan 17.
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.
像依维莫司这样的mTOR抑制剂可能会导致口腔炎，这通常是一种剂量限制性毒性。先前的临床研究表明，地塞米松漱口水可能有助于预防和/或治疗这种情况。联盟A221701是一项针对开始每日口服10mg依维莫司的患者的随机III期试验，该试验比较了预防性使用地塞米松漱口水（初始地塞米松组）与治疗性使用地塞米松漱口水（初始安慰剂组），以评估两个共同主要终点：mTOR抑制剂相关口腔炎（mIAS）的发生率，以及在8周治疗期内与mIAS相关疼痛的曲线下面积（AUC）。使用Fisher精确检验比较发生率，使用Wilcoxon秩和检验比较AUC。此外，我们使用Mann-Whitney U检验对依维莫司谷浓度与毒性之间的关联进行了探索性分析。由于入组缓慢，在39名患者被随机分组（19名进入初始安慰剂组，20名进入初始地塞米松组）后，该研究结束。在两个共同主要终点中，两组之间均未观察到显著差异；此外，我们发现全血依维莫司谷浓度与毒性之间没有关联。尽管受到入组不佳的限制，但这项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口水（在口腔疼痛的第一个迹象出现时开始使用）。
