SITEP (Phase 1 Unit), Department of Medicine, Institut Gustave Roussy, Villejuif, France.
Eur J Cancer. 2011 Oct;47(15):2249-55. doi: 10.1016/j.ejca.2011.03.017. Epub 2011 Apr 12.
Oral ulcers is a well-recognised adverse event (AE) of mTOR inhibitors. Paradoxically, little is known about its natural history, risk factors, and basic management.
AEs of 79 patients prospectively enrolled in 6 phase I-II studies testing everolimus were reviewed. The following parameters were analysed: incidence, severity, duration and associated AE. The association between OU and everolimus dose, pharmacokinetics and the effectiveness of empiric treatments were explored.
OU, grade 3-4 OU, prolonged time under OU and RCOU (recurrent and chronic oral ulcer) were observed in 72% 11%, 30% and 25% patients, respectively. Patients with antecedent of prior chemotherapy, with PS 1, or receiving everolimus in combination tended to present higher rates of prolonged time under OU and of grade 3-4 OU. As everolimus daily dose increased, the median time to OU was shorter, the median duration was longer and OU incidence tended to increase. Simultaneously, OU tended to be associated with higher everolimus exposure. None of the empiric treatments appeared effective against OU (preventive or curative intent).
Everolimus-induced OU is a frequent, recurrent and sometimes harmful complication. A dose effect relationship is displayed. Its daily management remains challenging. OU represents a key issue in the compliance of mTOR inhibitors.
口腔黏膜炎是 mTOR 抑制剂的一种常见不良反应（AE）。但令人费解的是，目前对于其自然病程、风险因素和基本管理措施，人们知之甚少。
我们回顾了 79 例接受依维莫司治疗的 I 期至 II 期前瞻性临床试验患者的 AE。分析了 AE 的发生率、严重程度、持续时间和相关 AE。探讨了 OU 与依维莫司剂量、药代动力学和经验性治疗效果之间的关系。
72%的患者出现 OU，30%的患者出现 3-4 级 OU，30%的患者出现 OU 持续时间延长，25%的患者出现 RCOU（复发性和慢性口腔黏膜炎）。既往接受过化疗、PS 为 1 分或与依维莫司联合治疗的患者，出现 OU 持续时间延长和 3-4 级 OU 的风险较高。随着依维莫司日剂量的增加，出现 OU 的中位时间缩短，OU 的中位持续时间延长，OU 的发生率也有增加的趋势。同时，OU 与依维莫司暴露量增加有关。任何经验性治疗方法（预防或治疗）似乎对 OU 均无效。
依维莫司引起的口腔黏膜炎是一种常见、复发性、有时甚至是有害的并发症。其呈现出剂量依赖性。其日常管理仍具挑战性。口腔黏膜炎是 mTOR 抑制剂依从性的关键问题。
