Oral Adverse Events Associated with Tyrosine Kinase and Mammalian Target of Rapamycin Inhibitors in Renal Cell Carcinoma: A Structured Literature Review

Learning Objectives After completing this course, the reader will be able to: Describe the oral manifestations that can appear with TKI/mTORI. Describe the limitations of the current oral assessment tools in assessing these novel presentations and list items needed to assess the presentations properly. This article is available for continuing medical education credit at CME.TheOncologist.com Background. Oral adverse events (OAEs) associated with multitargeted tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors (mTORIs) are underestimated but frequent and novel presentations of mucosal manifestations. Because optimal antitumor activity requires maintaining the optimal dose, it is essential to avoid unintended treatment delays or interruptions. Methods. We review the reported prevalence and appearance of OAEs with TKIs and mTORIs and the current oral assessment tools commonly used in clinical trials. We discuss the correlations between OAEs and hand–foot skin reaction (HFSR) and rash. Results. The reported prevalence of oral mucositis/stomatitis of any grade is 4% for pazopanib, 28% for sorafenib, 38% for sunitinib, 41% for temsirolimus, and 44% for everolimus. Oral lesions associated with these agents have been reported to more closely resemble aphthous stomatitis than OM caused by conventional agents. In addition, these agents may result in symptoms such as oral mucosal pain, dysgeusia, and dysphagia, in the absence of clinical lesions. Because of these factors, OAEs secondary to targeted agents may be underreported. In addition, a correlation between OAEs and HFSR was identified. Conclusions. OAEs caused by TKIs and mTORIs may represent dose‐limiting toxicities, especially considering the fact that even low grades of OAEs may be troubling to the patient. We discuss how these novel AEs can be assessed because current mucositis assessment tools have limitations. Prospective studies investigating the pathogenesis, risk factors, and management of OAEs are needed in order to minimize the impact on patient's health‐related quality of life. 摘要 背景 与多靶点酪氨酸激酶抑制剂（TKIs）及哺乳动物雷帕霉素靶蛋白抑制剂（mTORIs）相关口腔不良事件（ OAEs ）是发病率被低估但又常见的疾病，表现为粘膜异常。由于最佳的抗肿瘤活性要求必须保持最佳药物剂量，因而避免意外的治疗延误或者干扰是有必要的。 方法 我们回顾了已报告的 TKIs 及 mTORIs 相关性 OAEs 的流行病学及病理表现以及目前常应用于临床试验的口腔评估工具。我们讨论了 OAEs 与手足皮肤反应（ HFSR ）及皮疹之间的关系。 结果 已报告的各种程度的口腔粘膜炎症/口炎发病率为帕唑帕尼4%，索拉非尼28%，舒尼替尼38%，西罗莫司脂化物（41%），依维莫司（44%）。据报告，与上述药物相关的口腔病损较之于传统药物所导致的OM更类似于口疮性口炎。此外，上述药物可能导致诸如口腔粘膜疼痛、味觉障碍、吞咽困难等症状而无临床病损。因此，继发于靶点药物的OAEs可能被低估