Safety and efficacy of escalating doses of ingenol mebutate for field treatment of actinic keratosis on the full face, full balding scalp, or chest

Background: Actinic keratosis (AK) can affect large skin areas. Ingenol mebutate (IngMeb) gel (0.015% and 0.05%) is approved for topical treatment of AK in a single contiguous area of ~25 cm2. Objective: The study sought to determine the maximum tolerated dose (MTD), efficacy, and tolerability of IngMeb applied to AK on a contiguous area less than equal to 250 cm2. Methods: Part 1 determined the MTD of IngMeb at 7 concentrations for 2 or 3 days. Part 2 assessed efficacy and tolerability at the MTD and one dose lower for 2 or 3 days vs vehicle. Results: Four dosing regimens with an acceptable benefit-to-risk ratio were identified: 0.018% and 0.027% once daily for 2 or 3 days. Complete clearance at 8 weeks was achieved by 21.3% to 39.1% of IngMeb-treated patients vs 0% to 3.2% treated with vehicle. Composite local skin response scores peaked on the day after the last application, rapidly declined, and were near baseline at 2 weeks. Adverse events were predominantly mild or moderate. Limitations: The study evaluated a limited number of doses in a population of only white patients. Conclusion: IngMeb gel was effective and well tolerated as field treatment of AK on the full face, full scalp, and up to 250 cm2 on the chest.