title: Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis: A Randomized Clinical Trial.
abstract: OBJECTIVE
  Topical fluorouracil was demonstrated to be effective in reducing the number of actinic keratoses (AKs) for up to 6 months, but no randomized trials studied its long-term efficacy.
  
  
  OBJECTIVE
  To evaluate the long-term efficacy of a single course of fluorouracil cream, 5%, for AK treatment.
  
  
  METHODS
  The Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) trial was a randomized, double-blinded, placebo-controlled trial with patients from dermatology clinics at 12 VA medical centers recruited from 2009 to 2011 and followed up until 2013. Our study population comprised 932 veterans with 2 or more keratinocyte carcinomas in the 5 years prior to enrollment. The mean follow-up duration was 2.6 years in both treatment and control groups.
  
  
  METHODS
  Participants applied either topical fluorouracil cream, 5% (n = 468), or vehicle control cream (n = 464) to the face and ears twice daily for up to 4 weeks.
  
  
  METHODS
  This study reports on AK counts and treatments, which were secondary outcomes of the VAKCC trial. Actinic keratoses on the face and ears were counted by study dermatologists at enrollment and at study visits every 6 months. The number of spot treatments for AKs on the face and ears at semiannual study visits and in between study visits was recorded.
  
  
  RESULTS
  The number of AKs on the face and ears per participant was not different between the fluorouracil and control groups at randomization (11.1 vs 10.6, P > .10). After randomization, the fluorouracil group had fewer AKs compared with the control group at 6 months (3.0 vs 8.1, P < .001) and for the overall study duration (P < .001). The fluorouracil group also had higher complete AK clearance rates (38% vs 17% at 6 months) and fewer spot treatments at 6-month intervals, at study visits, and in between study visits during the trial (P < .01 for all). The fluorouracil group took longer to require the first spot AK treatment (6.2 months) compared with the control group (6.0 months) (hazard ratio, 0.69; 95% CI, 0.60-0.79). The number of hypertrophic AKs was not different between the 2 groups overall (P = .60), although there were fewer hypertrophic AKs in the fluorouracil group at 6 months (0.23 vs 0.41) (P = .05).
  
  
  CONCLUSIONS
  Our results indicate that a single course of fluorouracil cream, 5%, effectively reduces AK counts and the need for spot treatments for longer than 2 years.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier:NCT00847912.
authors.affiliation: Center for Dermatoepidemiology, Veterans Affairs (VA) Medical Center, Providence, Rhode Island2Department of Dermatology, Brown University, Providence, Rhode Island.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Pomerantz
authors.affiliation: Dermatology, Bay Pines VA Healthcare System, Bay Pines, Florida4Department of Internal Medicine (Dermatology), NOVA Southeastern University College of Osteopathic Medicine, Davie, Florida.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hogan
authors.affiliation: Dermatology, Edward Hines Jr VA Hospital, Hines, Illinois.
authors.forename: David
authors.initials: D
authors.lastname: Eilers
authors.affiliation: Dermatology, VA Palo Alto Health Care System, Palo Alto, California7Department of Dermatology, Stanford University Medical Center, Palo Alto, California.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Swetter
authors.affiliation: Dermatology, Atlanta VA Medical Center, Atlanta, Georgia9Department of Dermatology, Emory University, Atlanta, Georgia.
authors.forename: Suephy C
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Dermatology, VA San Diego Healthcare System, San Diego, California.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Jacob
authors.affiliation: Dermatology, Minneapolis VA Health Care System, Minneapolis, Minnesota12Department of Dermatology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Warshaw
authors.affiliation: Dermatology, Tennessee Valley Healthcare System, Nashville, Tennessee14Division of Dermatology, Vanderbilt University, Nashville, Tennessee.
authors.forename: George
authors.initials: G
authors.lastname: Stricklin
authors.affiliation: Dermatology, VA Medical Center, Denver, Colorado.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Dellavalle
authors.affiliation: Dermatology, Durham VA Medical Center, Durham, North Carolina17Department of Dermatology, Duke University, Durham, North Carolina.
authors.forename: Navjeet
authors.initials: N
authors.lastname: Sidhu-Malik
authors.affiliation: Dermatology, Boston VA Medical Center, Boston, Massachusetts.
authors.forename: Nellie
authors.initials: N
authors.lastname: Konnikov
authors.affiliation: Dermatology, Philadelphia VA Medical Center, Philadelphia, Pennsylvania20Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Victoria P
authors.initials: VP
authors.lastname: Werth
authors.affiliation: Dermatology, Miami VA Hospital, Miami, Florida22Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, Miami.
authors.forename: Jonette
authors.initials: J
authors.lastname: Keri
authors.affiliation: VA Cooperative Studies Coordinating Center, Boston, Massachusetts.
authors.forename: Robert
authors.initials: R
authors.lastname: Lew
authors.affiliation: Center for Dermatoepidemiology, Veterans Affairs (VA) Medical Center, Providence, Rhode Island2Department of Dermatology, Brown University, Providence, Rhode Island24Department of Dermatology, Rhode Island Hospital, Providence25Department of Epidemiology.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Weinstock
mesh_terms: D000287:Administration, Topical; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D055623:Keratosis, Actinic / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D012189:Retrospective Studies; D012867:Skin / Q000473:pathology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil