Supplementary Material for: Nintedanib-Induced Delayed Mucosal Healing after Adjuvant Radiation in a Case of Oropharyngeal Carcinoma

Since the launch of imatinib in 2001, tyrosine kinase inhibitors are being used in chemotherapy for a wide range of malignant tumors. Drugs that inactivate multiple molecular mechanisms are called multikinase inhibitors (MKIs). Nintedanib is a type of MKI that inhibits downstream cascades in three systems: vascular endothelial growth factor receptor, fibroblast growth factor receptor, and platelet-derived growth factor receptor inhibitions. It was initially developed as an anticancer drug for non-small-cell lung carcinoma; however, it was also found to inhibit the proliferation of fibroblasts associated with chronic inflammation in the lungs. Therefore, it is being more widely used to treat idiopathic pulmonary fibrosis, a benign disease, than as an antineoplastic agent. Several studies have reported adverse events associated with the concurrent use of MKIs with surgery or radiotherapy. Specifically, there has been a report cautioning against delayed wound healing associated with the use of nintedanib in patients undergoing surgery. However, there is no specific mention of its concurrent use during irradiation. We describe a case of a 72-year-old man with severely delayed recovery from radiation mucositis when nintedanib was being administered for benign disease.