Peddi Parvin F, Tetef Merry, Coluzzi Paul, Arzoo Karo K, Hu Eddie H, Berkowitz Maurice J, Chan David, Moore Dennis, Adams Brad, Wang Xiaoyan, Hurvitz Sara A
University of California, Los Angeles, 2336 Santa Monica Blvd., Suite 304, Santa Monica, CA 90404, USA.
University of California, Los Angeles, CA, USA.
Ther Adv Med Oncol. 2020 Nov 30;12:1758835920967259. doi: 10.1177/1758835920967259. eCollection 2020.
Stomatitis is a frequent dose limiting toxicity of everolimus, an approved therapy for patients with metastatic breast cancer. No randomized trials of a prophylactic measure to prevent mucositis have been reported.
We conducted a phase II, open-label trial in which patients with metastatic breast cancer starting everolimus were randomized to best supportive care (BSC) prophylactic use of an oral mucoadhesive, non-steroid containing mouth wash. The primary endpoint was rate of any grade stomatitis as reported by the treating physicians. Secondary endpoints were severity of stomatitis according to the Oral Mucositis Assessment Scale (OMAS) and rates of everolimus dose reduction or discontinuation due to mucositis.
Of 61 evaluable patients, 32 were randomized to and treated with oral mucoadhesive and 29 with BSC. Any grade stomatitis developed in 46.9% (15/32) of study arm and 65.5% (19/29) of BSC arm patients ( = 0.14). The difference between the two arms was significantly in favor of the mucoadhesive arm when mucositis was scored according to the OMAS with average score of 0.3 in study arm 0.5 in the control arm ( = 0.03). There were fewer dose adjustments or therapy discontinuations in the study arm compared with BSC (16% 31%, respectively) but the difference did not reach statistical significance.
Here we provide early evidence from the first randomized trial supporting the use of oral prophylactic mucoadhesive for everolimus-associated stomatitis. A trial comparing prophylactic oral mucoadhesive to steroid mouth wash may be warranted.
口腔炎是依维莫司常见的剂量限制性毒性反应，依维莫司是一种已获批用于转移性乳腺癌患者的治疗药物。目前尚无关于预防口腔黏膜炎的预防性措施的随机试验报道。
我们开展了一项II期开放标签试验，将开始使用依维莫司的转移性乳腺癌患者随机分为接受最佳支持治疗（BSC）组和预防性使用含口服黏膜黏附剂、不含类固醇的漱口水组。主要终点是治疗医师报告的任何级别的口腔炎发生率。次要终点是根据口腔黏膜炎评估量表（OMAS）评估的口腔炎严重程度以及因口腔黏膜炎导致的依维莫司剂量减少或停药率。
在61例可评估患者中，32例被随机分配至口服黏膜黏附剂组并接受该治疗，29例接受最佳支持治疗。研究组46.9%（15/32）的患者和最佳支持治疗组65.5%（19/29）的患者发生了任何级别的口腔炎（P = 0.14）。当根据OMAS对口腔黏膜炎进行评分时，两组之间的差异显著有利于黏膜黏附剂组，研究组平均评分为0.3，对照组为0.5（P = 0.03）。与最佳支持治疗组相比，研究组的剂量调整或治疗中断较少（分别为16%和31%），但差异未达到统计学意义。
在此，我们提供了来自第一项随机试验的早期证据，支持使用口服预防性黏膜黏附剂治疗依维莫司相关的口腔炎。可能有必要开展一项比较预防性口服黏膜黏附剂与类固醇漱口水的试验。
