title: A dose-finding trial with a novel ingenol derivative (ingenol disoxate: LEO 43204) for field treatment of actinic keratosis on full face or 250 cm2on the chest.
abstract: OBJECTIVE
  Actinic keratoses (AKs) may progress to squamous cell carcinoma and can occur in cancerized fields as sub-clinical and clinically visible lesions. Ingenol disoxate gel is a topical field therapy for AK. This Phase I/II trial aimed to assess the safety and efficacy of ingenol disoxate on full face or chest in patients with AKs.
  
  
  METHODS
  Part 1 was a phase-I, open-label, dose-escalation trial investigating the maximum tolerated dose of ingenol disoxate. Part 2 was a phase-II, randomized, double-blind, vehicle-controlled trial; patients were randomized 1:1:1:1 to ingenol disoxate 0.018%, 0.012%, 0.006% gel or vehicle for 2 consecutive days.
  
  
  RESULTS
  Reduction in AK count from baseline at Week 8 was significantly higher than with vehicle for all doses of ingenol disoxate gel (0.018%, 79.0%; 0.012%, 73.4%; 0.006%, 69.7%; vehicle; 42.3%; p < .001). Local skin responses peaked at Day 3 for all doses, rapidly declined, and reached mild levels at Week 2. Most adverse events were mild or moderate in intensity, and were most commonly application site pain/pruritus.
  
  
  CONCLUSIONS
  Ingenol disoxate gel is efficacious and well tolerated as field treatment for AKs on the full face or chest. Clinical Trial No.: NCT01922050.
authors.affiliation: a Department of Dermatology , Hop G. L. Dumont , Moncton , NB , Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Bourcier
authors.affiliation: b Department of Dermatology , Henry Ford Hospital , Detroit , MI , USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Stein Gold
authors.affiliation: c Guenther Research Inc. , London , ON , Canada.
authors.forename: Lyn
authors.initials: L
authors.lastname: Guenther
authors.affiliation: d LEO Pharma A/S , Ballerup , Denmark.
authors.forename: Camilla M
authors.initials: CM
authors.lastname: Andreassen
authors.affiliation: d LEO Pharma A/S , Ballerup , Denmark.
authors.forename: Johan
authors.initials: J
authors.lastname: Selmer
authors.affiliation: e Department of Dermatology , Icahn School of Medicine at Mount Sinai , New York , NY , USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Goldenberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004224:Diterpenes / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005145:Face / Q000473:pathology; D005260:Female; D006801:Humans; D055623:Keratosis, Actinic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000209:etiology; D015990:Placebo Effect; D011537:Pruritus / Q000209:etiology; D013909:Thorax / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D004224:Diterpenes; C000612882:LEO 43204
keywords: Actinic keratosis; field cancerization; ingenol disoxate; ingenol mebutate