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

Abstract

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. This study aimed to develop a treatment for inflammatory ulcers as one of the side effects of afatinib (Giotrif®), a secondgeneration 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.Conclusions: These results suggest that minocycline petrolatum applied locally prevents and repairs afatinibinduced skin disorders of non-small cell lung cancer patients. Histological examination of skin has provided insights into the mechanism of the occurrence of afatinib-related skin disorder and suggested the efficacy of minocycline topical application in clinical practice.

The relationship between medication literacy and skin adverse reactions in non-small-cell lung cancer patients undergoing targeted EGFR-TKI therapy

“…Currently, there is no consensus about the incidence of severe skin ADRs. For example, a 24% severe skin ADR rate was reported by Sano and colleagues, which is 1.5 times lower than the current investigation (39.9%) [ 37 ]. This difference may be because of the variation in the type of cancer and the type of drugs under investigation.…”

“…For example, the symptoms caused by skin ADRs could disturb patients’ sleep, detrimentally affect their self-esteem, and result in various social participation disorders [ 14 , 15 ]. Even worse, it was reported that the medication adherence of patients receiving EGFR-TKI-based targeted therapy was poor, with 32% of NSCLC patients terminating treatments due to skin toxicity reactions, which compromised the treatment effects [ 16 , 17 ].…”

Adverse reactions of targeted therapy in cancer patients: a retrospective study of hospital medical data in China

“…Meanwhile, compared with patients without ADRs, patients in ADRs group with orally administered drugs stopped taking medication and reduced drug dosage more due to being unable to tolerate the ADRs. The compliance of patients with orally targeted drugs decreased, while the incidence of missed dosages and not taking drugs on time increased, this was confirmed by Sano et al [ 34 ]. Therefore, it is important to manage ADRs well.…”

Effects of Smart Drugs on Cholinergic System and Non-Neuronal Acetylcholine in the Mouse Hippocampus: Histopathological Approach

“…Histological and immunohistochemical analyses were performed in accordance with the methods described previously [ 27 , 31 , 32 , 33 ]. For analysis using HE staining after sectioning for 4 mm thickness using Brain Slicer, the brain sections including the hippocampus were immersed in graded concentrations of ethanol, cleared in Lemosol A (Wako Pure Chemical Industries, Ltd., Osaka, Japan), and embedded in paraffin.…”