Safety Evaluations of Topical Vitamin K1 for Epidermal Growth Factor Receptor Inhibitor-Induced Rash

Papulopustular rash occurs in 80% of patients receiving Epidermal Growth Factor Receptor Inhibitor therapy for cancer. Topical vitamin K1, a phosphatase inhibitor, could reduce epidermal growth factor receptor inhibitor-induced rash. This preliminary safety study evaluated a novel topical 0.1% vitamin K1product for potential use in patients with epidermal growth factor receptor inhibitor-induced rash. Ten healthy subjects applied topical 0.1% vitamin K1 to healthy and tape stripped skin every 12 hours for five doses. Vitamin K1 levels were measured by ELISA in serum and plasma at 0, 26, and 50 hours. Vitamin K1 levels ranged between 0 to 8.22ng/ml. Bivariate correlative analyses showed no association between mean vitamin K1 concentration and time (r=0.008, p=0.930). Using a range of vitamin K1 concentrations (2.5 to 100ng/ml) that encompassed and exceeded the levels detected in our healthy subjects, we evaluated the ability of vitamin K1 to reverse cetixumab-induced Epidermal Growth Factor Receptor inhibition in A549 lung cancer cells. Vitamin K1 did not significantly change phosphorylated-Epidermal Growth Factor Receptor levels in cetuximab-treated cells (p>0.670). In conclusion, systemic vitamin K1 levels up to 100ng/ml would not interfere with epidermal growth factor receptor inhibitor therapy. Our next step is to test the effectiveness of our 0.1% topical VK1 formulation for Epidermal Growth Factor Receptor Inhibitor-induced rash in patients receiving epidermal growth factor receptor inhibitor therapy in a randomized, placebo-controlled, blinded study.