title: Low-dose 5-fluorouracil in combination with salicylic acid as a new lesion-directed option to treat topically actinic keratoses: histological and clinical study results.
abstract: BACKGROUND
  Actinic keratoses (AKs) arise after chronic sun exposure. Because long-term ultraviolet (UV) damage may induce proliferation of atypical keratinocytes, treatment of AKs is recommended.
  
  
  OBJECTIVE
  To compare 5-fluorouracil 0·5%/salicylic acid 10·0% [low-dose 5-FU/SA (Actikerall®)] with diclofenac 3% in hyaluronic acid (diclofenac HA) and vehicle for the treatment of AKs.
  
  
  METHODS
  This was a randomized, placebo-controlled, double-blind, parallel-group, multicentre trial. Patients received topical low-dose 5-FU/SA once daily, its vehicle or diclofenac HA twice daily for a maximum of 12 weeks. The final evaluation was at week 20. The primary objectives were to demonstrate the histological clearance rate of one predefined lesion. The secondary objectives were the improvement of treated lesions, tolerability and safety.
  
  
  RESULTS
  There were 470 patients with 4-10 AK lesions each (grade I or II) on the face/forehead or bald scalp included in the study. Low-dose 5-FU/SA was superior to diclofenac HA (P < 0·01) and vehicle (P < 0·0001) for histological clearance of one representative lesion 8 weeks post-treatment. In 72·0%, 59·1% and 44·8% of patients in the low-dose 5-FU/SA, diclofenac HA and vehicle groups, respectively, the week-20 biopsy revealed no AKs. Significantly more lesions were cleared with low-dose 5-FU/SA (74·5%) compared with diclofenac HA (54·6%; P < 0·001) or vehicle (35·5%; P< 0·001). Low-dose 5-FU/SA was superior in terms of complete clinical clearance: 55·4%, vs. diclofenac HA (32·0%, P < 0·001) and vehicle (15·1%P < 0·001). Application-site disorders (mainly burning and inflammation) were more frequent with low-dose 5-FU/SA but mainly of mild to moderate intensity.
  
  
  CONCLUSIONS
  Topical low-dose 5-FU/SA demonstrated higher histological and clinical clearance rates vs. diclofenac HA or vehicle. Low-dose 5-FU/SA is an effective lesion-directed treatment for AKs.
authors.affiliation: Department of Dermatology, Venereology and Allergy, Berlin University Medical Centre, Charité Skin Cancer Centre, Berlin, Germany. eggert.stockfleth@charite.de
authors.forename: E
authors.initials: E
authors.lastname: Stockfleth
authors.forename: H
authors.initials: H
authors.lastname: Kerl
authors.forename: T
authors.initials: T
authors.lastname: Zwingers
authors.forename: C
authors.initials: C
authors.lastname: Willers
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D004008:Diclofenac / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006820:Hyaluronic Acid / Q000627:therapeutic use; D007641:Keratolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D055623:Keratosis, Actinic / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020156:Salicylic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D007641:Keratolytic Agents; D004008:Diclofenac; D006820:Hyaluronic Acid; D020156:Salicylic Acid; D005472:Fluorouracil