Topical vitamin K3 (Vit K3, Menadione) prevents erlotinib and cetuximab-induced EGFR inhibition in the skin

3036 Background: The EGFR inhibitors erlotinib and cetuximab cause skin toxicity in about 75% of patients. The occurrence of skin toxicity correlates with clinical benefit. About half the patients with skin toxicity report significant discomfort. There are currently no scientifically based or proven methods for preventing or treating effectively the skin toxicity secondary to EGFR inhibitors. Methods: We screened a number of EGFR activators and phosphatase inhibitors for their ability to abrogate EGFR inhibition secondary to erlotinib and cetuximab in A431 cells. P-EGFR expression was assessed by western blot analysis. Vit K3 was selected for further in vivo studies. The skin toxicity secondary to the topical application of Vit K3 was evaluated in nude mice. The highest non-toxic concentration was used to determine the ability of topical Vit K3 to prevent EGFR inhibition in the skin of nude mice treated with EGFR inhibitors. Results: Vit K3 was the most potent EGFR activator identified, the maximum effect...