Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis: A Randomized Clinical Trial | Cancer Screening, Prevention, Control | JAMA Dermatology | JAMA Network
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Original Investigation
September 2015

Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis: A Randomized Clinical Trial

Author Affiliations
  • 1Center for Dermatoepidemiology, Veterans Affairs (VA) Medical Center, Providence, Rhode Island
  • 2Department of Dermatology, Brown University, Providence, Rhode Island
  • 3Dermatology, Bay Pines VA Healthcare System, Bay Pines, Florida
  • 4Department of Internal Medicine (Dermatology), NOVA Southeastern University College of Osteopathic Medicine, Davie, Florida
  • 5Dermatology, Edward Hines Jr VA Hospital, Hines, Illinois
  • 6Dermatology, VA Palo Alto Health Care System, Palo Alto, California
  • 7Department of Dermatology, Stanford University Medical Center, Palo Alto, California
  • 8Dermatology, Atlanta VA Medical Center, Atlanta, Georgia
  • 9Department of Dermatology, Emory University, Atlanta, Georgia
  • 10Dermatology, VA San Diego Healthcare System, San Diego, California
  • 11Dermatology, Minneapolis VA Health Care System, Minneapolis, Minnesota
  • 12Department of Dermatology, University of Minnesota, Minneapolis, Minnesota
  • 13Dermatology, Tennessee Valley Healthcare System, Nashville, Tennessee
  • 14Division of Dermatology, Vanderbilt University, Nashville, Tennessee
  • 15Dermatology, VA Medical Center, Denver, Colorado
  • 16Dermatology, Durham VA Medical Center, Durham, North Carolina
  • 17Department of Dermatology, Duke University, Durham, North Carolina
  • 18Dermatology, Boston VA Medical Center, Boston, Massachusetts
  • 19Dermatology, Philadelphia VA Medical Center, Philadelphia, Pennsylvania
  • 20Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania
  • 21Dermatology, Miami VA Hospital, Miami, Florida
  • 22Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, Miami
  • 23VA Cooperative Studies Coordinating Center, Boston, Massachusetts
  • 24Department of Dermatology, Rhode Island Hospital, Providence
  • 25Department of Epidemiology, Brown University, Providence, Rhode Island
JAMA Dermatol. 2015;151(9):952-960. doi:10.1001/jamadermatol.2015.0502
Abstract

Importance  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.

Design, Setting, and Participants  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.

Interventions  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.

Main Outcomes and Measures  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 and Relevance  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.

Trial Registration  clinicaltrials.gov Identifier:NCT00847912

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