Introduction
Erlotinib, a tyrosine kinase inhibitor (EGFR-TKI), its use is frequently accompanied by significant cutaneous side effects, including facial dermatitis and hair loss. Previous research suggests that substance P (SP), a neuropeptide, is a major mediator of this skin toxicity. Given aprepitant’s role as an SP receptor antagonist, this study aimed to assess the efficacy of topical aprepitant in mitigating these skin side effects induced by erlotinib treatment.
Methods
A 12-week study was conducted using rats that were administered erlotinib in their diet. Facial dermatitis and hair loss developed after six weeks of treatment, becoming most severe by week 12. Rats received topical aprepitant three times weekly to the facial area. Skin biopsies and blood samples were collected at the end of the study to evaluate neutrophil activity, oxidative stress markers, and leukocyte infiltration.
Key Findings
- Dose-dependent effect: Topical aprepitant significantly inhibited facial dermatitis and hair loss in a dose-dependent manner, with up to 70% reduction in symptoms observed.
- Reduction of oxidative stress: Neutrophil superoxide production and elevated plasma 8-isoprostane levels, both markers of oxidative stress, were significantly suppressed in rats treated with topical aprepitant.
- Inhibition of leukocyte infiltration: Facial skin samples showed increased leukocyte (CD11b-positive) infiltration in erlotinib-treated rats. This infiltration was substantially reduced by topical aprepitant treatment.
- Neurogenic inflammation: The study suggests that neurogenic inflammation, driven by substance P, plays a critical role in the development of EGFR-TKI-induced cutaneous toxicity.
- Systemic effects of topical treatment: Despite being applied topically, aprepitant exhibited systemic effects, reducing oxidative stress and leukocyte infiltration, suggesting adequate absorption through the skin.
Conclusion
Topical application of aprepitant effectively reduced erlotinib-induced cutaneous toxicity by inhibiting neurogenic inflammation and oxidative stress. These results suggest that aprepitant could offer a novel and localized treatment option for managing EGFR-TKI-induced skin toxicity. Further clinical research is needed to validate these findings and explore the potential for clinical application.
Link to the study: https://shorturl.at/ZCmph
