title: Ingenol mebutate in the treatment of 'Hydroxyurea-induced Squamous Dysplasia': a single centre experience.
abstract: BACKGROUND
  'Hydroxyurea-induced Squamous Dysplasia' (HISD) is a cutaneous side-effect related to chronic oral treatment with Hydroxyurea. Ingenol mebutate gel is a topical drug approved for the treatment of multiple, non-hypertrophic actinic keratoses (AK) localized within a limited cancerization field. Since HISD may be considered as a drug-induced variant of classic AK, ingenol mebutate is likely to have therapeutic effects.
  
  
  OBJECTIVE
  The aim of this study was to evaluate efficacy and safety of ingenol mebutate 150 mcg/g and 500 mcg/g, as a treatment of HISD lesions on face/scalp and trunk/extremities respectively.
  
  
  METHODS
  Seven areas with a mean of lesions of 5.9 ± 1.7 in five patients with HISD were treated. Patients with lesions on face/scalp self-treated a 25 cm(2) skin affected area with ingenol mebutate gel 150 mcg/g, one tube daily for 3 days. Patients with lesions localized on trunk/extremities treated the same size affected area with ingenol mebutate gel 500 mcg/g, one tube daily for 2 days. Clinical assessment and count of HISD lesions has been performed by an experienced dermatologist at day 0, at day 57, and at time of last feasible follow-up visit (median 337 days). Safety assessment included the report of all SAEs.
  
  
  RESULTS
  At 57-day follow-up, we observed an overall response rate (ORR) - the sum of Complete Responses (CR) + Partial Responses (PR) - of 87.5%, with a 57.1% CR, and a 78.0% total lesions' reduction compared to time 0 (P < 0.01). On a median follow-up of 337 days, we observed a long-term ORR of 71.4%, a 57.1% CR ratio and a 65.9% total lesions' reduction compared to time 0 (P = 0.01). No severe (grade 3-4) adverse events have been reported.
  
  
  CONCLUSIONS
  Although obtained in a small case series, these encouraging data lead us to propose ingenol mebutate gel as a possible treatment for HISD.
authors.affiliation: Department of Surgery and Translational Medicine, Division of Dermatology, University of Florence, Florence, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Grandi
authors.affiliation: Department of Surgery and Translational Medicine, Division of Dermatology, University of Florence, Florence, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Delfino
authors.affiliation: Department of Surgery and Translational Medicine, Division of Dermatology, University of Florence, Florence, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Pimpinelli
mesh_terms: D000368:Aged; D004224:Diterpenes / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000187:drug effects*; D012871:Skin Diseases / Q000139:chemically induced*
chemical_list: C486592:3-ingenyl angelate; D004224:Diterpenes; D006918:Hydroxyurea