title: Topical Ingenol Mebutate: A New Treatment Modality for Multiple Actinic Keratoses and Field Cancerization.
abstract: BACKGROUND
  Ingenol mebutate gel is a recent stirring weapon recommended for the treatment of multiple actinic keratoses (AKs) and field cancerization. This review brings a summary of recent data on the treatment of AKs with ingenol mebutate (IM) providing critical commentary with regard to drug's characteristics, drug's safety profile, treatment regimen, treatment outcome, patient compliance, AK recurrence, costeffectiveness and cost-utility, as well as guidelines for the management of the treatment of AK.
  
  
  METHODS
  We undertook a structured search of bibliographic databases for peer-reviewed scientific articles, including review articles, original research articles as well as case report articles based on inclusion/exclusion criteria. Reports on ingenol mebutate from U.S. Food and Drug Administration and European Medical Agency were also included.
  
  
  RESULTS
  Sixty-six papers were included in this review. We report current data on ingenol mebutate chemical properties, pharmacology, efficacy, safety, and tolerability, potential new indications in dermatology, costeffectiveness, and cost-utility analysis.
  
  
  CONCLUSIONS
  Treatment of AKs is necessary in order to prevent possible transition to invasive SCC. Although the mechanism of action of ingenol mebutate is not fully elucidated, dual mechanism of action is presumed. Ingenol mebutate is an effective and cost-saving topical agent for the treatment of AK, especially multiple AKs and field cancerization, with acceptable safety profile. It may also have perspective in dermatology regarding the treatment of superficial BCC, Bowen disease, actinic cheilitis, and anogenital warts that has to be evaluated in clinical trials. Patients' adherence to recommended treatment regimen and auspicious safety profile make this drug attractive.
authors.affiliation: Department of Dermatovenereology, University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb. Croatia.
authors.forename: Kresimir
authors.initials: K
authors.lastname: Kostovic
authors.affiliation: Department of Infectious Diseases and Dermatovenereology, General Hospital Sibenik, Sibenik. Croatia.
authors.forename: Sandra Jerkovic
authors.initials: SJ
authors.lastname: Gulin
authors.affiliation: Department of Dermatovenereology, University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb. Croatia.
authors.forename: Zrinka Bukvic
authors.initials: ZB
authors.lastname: Mokos
authors.affiliation: Department of Dermatovenereology, University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb. Croatia.
authors.forename: Romana
authors.initials: R
authors.lastname: Ceovic
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D055623:Keratosis, Actinic / Q000188:drug therapy*; D015394:Molecular Structure; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D013329:Structure-Activity Relationship
chemical_list: C486592:3-ingenyl angelate; D000970:Antineoplastic Agents; D004224:Diterpenes
keywords: Euphorbia peplus; Ingenol mebutate; PEP005; actinic keratosis; field therapy; ingenol 3-angelate