PEP005 (ingenol mebutate) gel, a novel agent for the treatment of actinic keratosis: results of a randomized, double-blind, vehicle-controlled, multicentre, phase IIa study.
The sap of the plant Euphorbia peplus is a traditional remedy for skin conditions, including actinic keratosis. The active constituent of the sap is ingenol mebutate (ingenol-3-angelate), formerly known as PEP005. This randomized, double-blind, vehicle-controlled, phase IIa study investigated the safety (and secondarily the efficacy) of two applications of ingenol mebutate gel in 58 patients with biopsy-confirmed actinic keratosis. Five preselected lesions were treated with ingenol mebutate gel, 0.0025%, 0.01% or 0.05%, or vehicle gel, on days 1 and 2 (Arm A) or days 1 and 8 (Arm B). There were no significant differences in tolerability or efficacy between Arms A and B. Treatment was well tolerated. The most common local skin responses were dose-related erythema, flaking/scaling/dryness and scabbing/crusting. Efficacy was greatest with ingenol mebutate gel, 0.05%, which resulted in complete clinical clearance of 71% of treated lesions (P < 0.0001 vs vehicle gel). In addition, 67% of patients treated with ingenol mebutate gel, 0.05% had clinical clearance of at least four of five treated lesions (P = 0.0185 vs vehicle gel). Ingenol mebutate gel is being developed as a short-course topical therapy for actinic keratosis and non-melanoma skin cancer.
Siller
Greg
G
Siller Medical Pty Ltd and Dermatology Group, The University of Queensland, Queensland, Australia. sillermedical@bigpond.com
Gebauer
Kurt
K
Welburn
Peter
P
Katsamas
Janelle
J
Ogbourne
Steven M
SM
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001132:Arm / Q000473:pathology; D001315:Australia; D004224:Diterpenes / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004952:Esters / Q000627:therapeutic use*; D005145:Face / Q000473:pathology; D005260:Female; D005782:Gels / Q000627:therapeutic use; D006801:Humans; D055623:Keratosis, Actinic / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012535:Scalp / Q000473:pathology; D016896:Treatment Outcome
C486592:3-ingenyl angelate; D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D004952:Esters; D005782:Gels