title: Lack of activity of betulin-based Oleogel-S10 in the treatment of actinic keratoses: a randomized, multicentre, placebo-controlled double-blind phase II trial.
abstract: BACKGROUND
  Betulinic acid and other triterpenes have shown strong antitumour activity in vitro and in vivo. A triterpene extract of birch bark formed the base of Oleogel-S10 and allowed topical application. Two previous trials have shown efficacy and tolerability in the treatment of actinic keratoses (AKs) with betulin-based Oleogel-S10.
  
  
  OBJECTIVE
  To confirm the efficacy and tolerability/safety of Oleogel-S10 in the treatment of AKs in a multicentre placebo-controlled study.
  
  
  METHODS
  Patients (n = 165) were treated topically for 3 months in a four-arm parallel study design, randomly allocated to A (n = 53) Oleogel-S10 once daily, B (n = 51) Oleogel-S10 twice daily, or C (n = 25) or D (n = 28) placebo (petroleum jelly) once or twice daily, respectively. Clinical efficacy in this double-blind study was assessed by the investigators. Final and baseline biopsies were evaluated by central histopathology.
  
  
  RESULTS
  Complete clearance of the target lesions was seen in 4% of patients in group A and 7% in group B, but not in the placebo groups. A clearance rate of > 75% was seen for 15% and 18% of patients in groups A and B, respectively, and for 13% in the placebo groups. These differences were not statistically significant. Histopathologically, 43·9% of patients showed a downgrading or clearance of the marker AK with no significant differences between the groups. Treatment with Oleogel-S10 was well tolerated. The tolerability as assessed by the investigator was mostly 'very good' (78·8%), followed by 'good' (18·2%) and only 1·2% assessed it as 'intolerable'. Patient-assessed tolerability was graded mostly 'very good' (56·4%) or 'good' (34·5%).
  
  
  CONCLUSIONS
  Treatment with Oleogel-S10 was well tolerated during a treatment period of 3 months, yet was no better than placebo in terms of efficacy in the treatment of AKs.
authors.affiliation: Center for Dermatooncology, Department of Dermatology, University Hospital Tübingen, Tübingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Pflugfelder
authors.forename: E
authors.initials: E
authors.lastname: Andonov
authors.forename: B
authors.initials: B
authors.lastname: Weide
authors.forename: T
authors.initials: T
authors.lastname: Dirschka
authors.forename: C
authors.initials: C
authors.lastname: Schempp
authors.forename: E
authors.initials: E
authors.lastname: Stockfleth
authors.forename: A
authors.initials: A
authors.lastname: Stratigos
authors.forename: S
authors.initials: S
authors.lastname: Krüger-Krasagakis
authors.forename: J
authors.initials: J
authors.lastname: Bauer
authors.forename: C
authors.initials: C
authors.lastname: Garbe
authors.forename: T K
authors.initials: TK
authors.lastname: Eigentler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D055623:Keratosis, Actinic / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009930:Organic Chemicals / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D016896:Treatment Outcome; D014315:Triterpenes / Q000008:administration & dosage* / Q000009:adverse effects; D000094062:Betulinic Acid
chemical_list: D003879:Dermatologic Agents; D009930:Organic Chemicals; D014315:Triterpenes; C016021:oleogels; C002503:betulin; D000094062:Betulinic Acid