US Oncology Research, Inc., The Woodlands, Texas, USA.
Yakima Valley Memorial Hospital/North Star Lodge, Yakima, Washington, USA.
Oncologist. 2019 Sep;24(9):1153-1158. doi: 10.1634/theoncologist.2018-0340. Epub 2019 Mar 4.
Mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis (mIAS) is a frequent adverse event (AE) associated with mTOR inhibitor therapy and can impact treatment adherence. The objectives are to evaluate two steroid-based mouthrinses for preventing/ameliorating mIAS in patients with metastatic breast cancer (MBC) treated with everolimus.
This prospective, randomized phase II study enrolled 100 postmenopausal patients with hormone receptor-positive MBC within the US Oncology Network who were initiating therapy with an aromatase inhibitor + everolimus (AIE; 10 mg/day). Patients were randomized to prophylactic therapy with one of two oral rinses (Arm 1: Miracle Mouthwash [MMW] 480 mL recipe: 320 mL oral Benadryl [diphenhydramine; Johnson & Johnson, New Brunswick, NJ, USA], 2 g tetracycline, 80 mg hydrocortisone, 40 mL nystatin suspension, water; or Arm 2: prednisolone [P] 15 mg/5 mL oral solution, 1.8% alcohol). Patients were instructed to swish/expectorate 10 mL of the assigned rinse for 1-2 minutes four times daily starting with day 1 of AIE treatment, for the first 12 weeks.
A total of 100 patients received treatment (49 MMW; 51 P). The incidence of stomatitis/oral AEs during the first 12 weeks was 35% ( = 17/49) and 37% (19/51) in the MMW and P arms, respectively. The incidence of grade 2 oral AEs was 14% (7/49) and 12% (6/51) with MMW or P, respectively. There were two grade 3 oral AEs (MMW arm) and no grade 4 events. There was one everolimus dose reduction (MMW) and six dose delays (four MMW, two P) and one dose reduction + delay (MMW) during the first 12 weeks of treatment. No patients stopped steroid mouthwash therapy because of rinse-related toxicity.
Prophylactic use of steroid-containing oral rinses can prevent/ameliorate mIAS in patients with MBC treated with AIE. MMW + hydrocortisone is an affordable option, as is dexamethasone oral rinse.
This prospective phase-II study showed that two steroid-containing mouthrinses substantially reduced incidences of all-grade and grade ≥2 stomatitis and related oral adverse events (AEs), and the number of everolimus dose-delays and/or dose-reduction in metastatic breast cancer (MBC) patients receiving everolimus treatment plus an aromatase inhibitor. Both oral rinses were well tolerated and demonstrated similar efficacy. Prophylactic use of steroid mouth rinse provides a cost-effective option that substantially decreases the incidence and severity of mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis and related oral AEs as well as the need for dose modification in MBC patients undergoing treatment with an mTOR inhibitor.
雷帕霉素靶蛋白（mTOR）抑制剂相关性口腔炎（mIAS）是一种与 mTOR 抑制剂治疗相关的常见不良反应（AE），可影响治疗依从性。本研究的目的是评估两种基于类固醇的漱口水在接受依维莫司治疗的转移性乳腺癌（MBC）患者中预防/改善 mIAS 的效果。
这是一项在美国肿瘤学网络中进行的前瞻性、随机 II 期研究，纳入了 100 名正在接受芳香酶抑制剂+依维莫司（AIE；10mg/天）治疗的绝经后激素受体阳性 MBC 患者。患者随机接受两种口腔漱口水之一的预防性治疗（Arm 1：Miracle Mouthwash [MMW] 480mL 配方：320mL 口服苯海拉明[苯那君；强生，新泽西州新不伦瑞克]，2g 四环素，80mg 氢化可的松，40mL 制霉菌素混悬液，水；或 Arm 2：泼尼松[P] 15mg/5mL 口服溶液，1.8%酒精）。患者被指示从 AIE 治疗的第 1 天开始，每天使用指定的漱口水漱口/吐出 10mL，每次 1-2 分钟，共 4 次，持续 12 周。
共有 100 名患者接受了治疗（MMW 组 49 名，P 组 51 名）。在第 12 周内，口腔炎/口腔 AE 的发生率分别为 MMW 组 35%（ = 17/49）和 P 组 37%（19/51）。2 级口腔 AE 的发生率分别为 MMW 组 14%（7/49）和 P 组 12%（6/51）。有 2 例 3 级口腔 AE（MMW 组），无 4 级事件。在治疗的第 12 周内，有 1 例 Everolimus 剂量减少（MMW）和 6 例剂量延迟（MMW 4 例，P 2 例），以及 1 例剂量减少+延迟（MMW）。没有患者因漱口水相关毒性而停止类固醇口腔冲洗治疗。
预防性使用含类固醇的口腔冲洗液可以预防/改善接受 AIE 治疗的 MBC 患者的 mIAS。MMW+氢化可的松是一种负担得起的选择，地塞米松口腔冲洗液也是如此。
这项前瞻性 II 期研究表明，两种含类固醇的漱口液可显著降低接受依维莫司联合芳香酶抑制剂治疗的转移性乳腺癌（MBC）患者的全级和 2 级及以上口腔炎及相关口腔不良事件（AE）的发生率，以及需要依维莫司剂量调整的发生率。两种漱口液均耐受良好，疗效相似。预防性使用类固醇口腔冲洗液可提供一种具有成本效益的选择，可显著降低 mTOR 抑制剂相关性口腔炎及相关口腔 AE 的发生率和严重程度，以及接受 mTOR 抑制剂治疗的 MBC 患者需要进行剂量调整的发生率。
