Department of Breast and Endocrine Surgery, Tokai University School of Medicine, Tokyo, Japan.
Department of Breast and Endocrine Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Oncologist. 2020 Feb;25(2):e223-e230. doi: 10.1634/theoncologist.2019-0382. Epub 2019 Oct 8.
The incidence of oral mucositis (any grade) after everolimus treatment is 58% in the general population and 81% in Asian patients. This study hypothesized that professional oral care (POC) before everolimus treatment could reduce the incidence of everolimus-induced oral mucositis.
This randomized, multicenter, open-label, phase III study evaluated the efficacy of POC in preventing everolimus-induced mucositis. Patients were randomized into POC and control groups (1:1 ratio) and received everolimus with exemestane. Patients in the POC group underwent teeth surface cleaning, scaling, and tongue cleaning before everolimus initiation and continued to receive weekly POC throughout the 8-week treatment period. Patients in the control group brushed their own teeth and gargled with 0.9% sodium chloride solution or water. The primary endpoint was the incidence of all grades of oral mucositis. We targeted acquisition of 200 patients with a 2-sided type I error rate of 5% and 80% power to detect 25% risk reduction.
Between March 2015 and December 2017, we enrolled 175 women from 31 institutions, of which five did not receive the protocol treatment and were excluded. Over the 8 weeks, the incidence of grade 1 oral mucositis was significantly different between the POC group (76.5%, 62 of 82 patients) and control group (89.7%, 78 of 87 patients; p = .034). The incidence of grade 2 (severe) oral mucositis was also significantly different between the POC group (34.6%, 28 of 82 patients) and control group (54%, 47 of 87 patients; p = .015). As a result of oral mucositis, 18 (22.0%) patients in the POC group and 28 (32.2%) in the control group had to undergo everolimus dose reduction.
POC reduced the incidence and severity of oral mucositis in patients receiving everolimus and exemestane. This might be considered as a treatment option of oral care for patients undergoing this treatment. Clinical trial identification number: NCT02069093.
The Oral Care-BC trial that prophylactically used professional oral care (POC), available worldwide, did not show a greater than 25% difference in mucositis. The 12% difference in grade 1 or higher mucositis and especially the ∼20% difference in grade 2 mucositis are likely clinically meaningful to patients. POC before treatment should be considered as a treatment option of oral care for postmenopausal patients who are receiving everolimus and exemestane for treatment of hormone receptor-positive, HER2-negative advanced breast cancer and metastatic breast cancer. However, POC was not adequate for prophylactic oral mucositis in these patients, and dexamethasone mouthwash prophylaxis is standard treatment before everolimus.
依维莫司治疗后口腔黏膜炎（任何级别）的发生率在普通人群中为 58%，在亚洲患者中为 81%。本研究假设在依维莫司治疗前进行专业口腔护理（POC）可以降低依维莫司引起的口腔黏膜炎的发生率。
这是一项随机、多中心、开放性、III 期研究，旨在评估 POC 预防依维莫司诱导性黏膜炎的疗效。患者被随机分为 POC 组和对照组（1:1 比例），并接受依维莫司联合依西美坦治疗。POC 组患者在开始依维莫司治疗前进行牙齿表面清洁、刮治和舌清洁，并在 8 周治疗期间每周接受 POC。对照组患者自行刷牙并用 0.9%氯化钠溶液或水漱口。主要终点是所有级别口腔黏膜炎的发生率。我们目标纳入 200 例患者，双侧检验的Ⅰ类错误率为 5%，80%的效能检测到 25%的风险降低。
2015 年 3 月至 2017 年 12 月，我们从 31 家机构共招募了 175 名女性患者，其中 5 名患者未接受协议治疗，被排除在外。在 8 周的时间里，POC 组（76.5%，62/82 例）和对照组（89.7%，78/87 例）的口腔黏膜炎 1 级发生率差异有统计学意义（p =.034）。POC 组（34.6%，28/82 例）和对照组（54%，47/87 例）的口腔黏膜炎 2 级（严重）发生率也有显著差异（p =.015）。由于口腔黏膜炎，POC 组 18 例（22.0%）和对照组 28 例（32.2%）患者需要减少依维莫司的剂量。
POC 降低了接受依维莫司和依西美坦治疗的患者口腔黏膜炎的发生率和严重程度。这可以被认为是接受这种治疗的患者进行口腔护理的一种治疗选择。临床试验注册号：NCT02069093。
Oral Care-BC 试验预防性使用了全球范围内都可获得的专业口腔护理（POC），但并未显示口腔黏膜炎的差异大于 25%。1 级或更高级别的口腔黏膜炎发生率差异 12%，特别是 2 级口腔黏膜炎发生率差异约 20%，对患者可能具有临床意义。对于正在接受依维莫司和依西美坦治疗激素受体阳性、HER2 阴性晚期乳腺癌和转移性乳腺癌的绝经后患者，治疗前的 POC 应被视为口腔护理的一种治疗选择。然而，在这些患者中，POC 并不能充分预防口腔黏膜炎，在接受依维莫司治疗前，地塞米松漱口液预防是标准治疗。
