Hanke C William, Berman Brian, Swanson Neil, Pariser David M, Weiss Jonathan S, Bukhalo Michael, Skov Torsten, Villumsen John, Siegel Daniel
J Drugs Dermatol. 2017 May 1;16(5):438-444.
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.
J Drugs Dermatol. 2017;16(5):438-444.
.光化性角化病（AK）可累及大面积皮肤。鬼臼毒素（IngMeb）凝胶（0.015%和0.05%）被批准用于局部治疗面积约25平方厘米的单个连续区域的AK。
本研究旨在确定将IngMeb应用于面积小于或等于250平方厘米的连续区域的AK时的最大耐受剂量（MTD）、疗效和耐受性。
第1部分确定了7种浓度的IngMeb在2或3天内的MTD。第2部分评估了MTD和低一个剂量的IngMeb在2或3天内与赋形剂相比的疗效和耐受性。
确定了四种具有可接受的风险效益比的给药方案：0.018%和0.027%，每日一次，持续2或3天。IngMeb治疗的患者中有21.3%至39.1%在8周时完全清除，而赋形剂治疗的患者为0%至3.2%。复合局部皮肤反应评分在最后一次应用后的第二天达到峰值，迅速下降，并在2周时接近基线。不良事件主要为轻度或中度。
该研究仅在白人患者群体中评估了有限数量的剂量。
IngMeb凝胶作为面部、头皮和胸部高达250平方厘米的AK区域治疗有效且耐受性良好。
《皮肤药物学杂志》。2017；16（5）：438 - 444。
