Long-term Follow-up Study of Ingenol Mebutate Gel for the Treatment of Actinic Keratoses

Abstract

Importance: Ingenol mebutate is the active agent (a macrocyclic diterpene ester) in the sap of the plant Euphorbia peplus. This herb has been used as a traditional remedy for several different skin lesions, including skin cancers.Objective: To assess 12-month recurrence rates and safety associated with ingenol mebutate gel treatment in patients who previously had achieved complete clearance of actinic keratoses. Design and Setting:The treatment area was observed for recurrence for 12 months after the original study. Patients were treated in an outpatient setting.Participants: Patients received ingenol mebutate gel, 0.015%, daily for 3 consecutive days for actinic keratoses on the face or scalp or ingenol mebutate gel, 0.05%, daily for 2 consecutive days for actinic keratoses on the trunk or extremities. Study participants had achieved complete clearance in a prespecified 25-cm 2 area at day 57 of their original trial. Main Outcome Measures:Recurrence rates and safety were assessed.Results: In total, 108 patients with complete clearance of face or scalp lesions in the original trial and 76 patients with complete clearance of trunk or extremity lesions in the original trial were enrolled in the 12-month observational follow-up study. Of these, 100 patients (face or scalp) and 71 patients (trunk or extremities) completed all 12 months. The sustained lesion reduction rates compared with baseline were 87.2% for the face or scalp and 86.8% for the trunk or extremities. The estimated median times to recurrence were 365 days (face or scalp) and 274 days (trunk or extremities). There were no safety concerns during the follow-up period. Conclusion and Relevance:Ingenol mebutate gel applied as field therapy for 2 or 3 consecutive days to treat actinic keratoses produced clinically relevant sustained clearance and long-term lesion reduction.

Ingenol Mebutate 0.06% Gel for Field Treatment of Actinic Keratosis on 250 cm2 of Skin on Trunk and Extremities: A Randomized Dose-Finding Trial

“…5 Studies have generally focused on the face and scalp [14][15][16][17] rather than the extremities, where AK lesions are more difficult to treat and have shorter remission times. 10 Partial, but not complete, clearance results from the current trial, investigating treatment in the trunk and extremities, compare well with two previous studies with imiquimod 2.5% and 3.75% that investigated a scalp/facial treatment area > 25 cm 2 . 18,19 In those studies, complete clearance rates were 30.6% and 35.6% for 2-week 18 and 25.0% and 34.0% for 3-week on/off/on treatment regimens.…”

“…9 The treatment effect was maintained long term. 10 Some patients, however, may require treatment over areas larger than 25 cm 2 .…”

Ingenol Mebutate for Lentigo Maligna: A Case Report

“…Ingenol mebutate has been registered in the USA and Europa as a local treatment for actinic keratosis [7][8][9][10] . In addition to its approved use, ingenol mebutate has emerged in the last years as an efficient topical agent for the treatment of Bowen's disease [11] , superficial basal cell carcinoma [12] and molluscum contagiosum [13] .…”

Non-melanoma Skin Cancer in Canada Chapter 3: Management of Actinic Keratoses

“…Eleven percent of facial/scalp AK patients and 22% of truncal/acral AK patients underwent cryosurgery or some other treatment for AKs during the study period. 56 …”