Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer

Background While epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors(TKIs) exert a breakthrough effect, the incidence of skin disorders as a side effect has significantly reduced patients' quality of life. Objective This study aimed to develop a treatment for inflammatory ulcers as one of the side effects of afatinib (Geotrif®), a second-generation EGFR-TKI, and established a skin disorder mouse model to investigate the protective effect of minocycline. Methods First, under inhalation anesthesia with isoflurane, the back of a male ddy mouse was shaved, and afatinib petrolatum was applied alone or in combination with minocycline to observe the state of the skin and measure transepidermal water transpiration (TEWL). Next, afatinib was administered orally to mice, and minocycline petrolatum was applied to observe whether the skin disorder was prevented and its effect on repair of the skin disorder. Results Skin injury occurred on the back of the mouse following afatinib (1 mg/g in petrolatum) application, and scab formation was observed. Application of minocycline prevented and improved the skin disorder caused by afatinib. When the minocycline-petrolatum mixture was applied to the mouse that developed the skin disorder, a significant improvement in TEWL was observed, and skin repair was observed macroscopically. Discussion These results suggest that minocycline applied both locally and orally prevents and repairs afatinib-induced skin disorders. Histological examination of skin elucidated the mechanism of the occurrence of the EGFR-TKI-related skin disorder and suggested the efficacy of minocycline topical application in clinical practice.