Long-term efficacy of topical fluorouracil cream, 5%, for treating actinic keratosis: A randomized clinical trial

Hyemin Pomerantz, Daniel Hogan, David Eilers, Susan M. Swetter, Suephy C. Chen, Sharon E. Jacob, Erin M. Warshaw, George Stricklin, Robert P. Dellavalle, Navjeet Sidhu-Malik, Nellie Konnikov, Victoria P. Werth, Jonette Keri, Robert Lew, Martin A. Weinstock, Kimberly Marcolivio, John J. DiGiovanna, Ryan Ferguson, Robert Ringer, Jean YoonCiaran S. Phibbs, Ken Kraemer, James W. Swan, Kristin Nord, Brian Pollack, Stephen Kempiak, Whitney High, Nicole Fett, Russell P. Hall, Javier Alonso-Llamazares, Georgette Rodriguez, Lorine Sisler, Mary O'Sullivan, Sonya Wilson, Madhuri Agrawal, Debra Bartenfeld, Keith Nicalo, Deb Johnson, Patricia Parks, Barbara Bidek, Nancy Boyd, Barbara Watson, Dianne Wolfe, Mark Zacheis, Joyce Okawa, Mary Ann Iannacchione, Jalima Quintero, Subbarayudu Cuddapah, Karen Muller, Vanessa Lichon, Todd Anhalt, Vista Khosravi, Zakia Rahman, Leslie Lawley, Roberta McCoy, Neal Foman, Andrea Bershow, John Zic, Jami Miller, H. Alan Arbuckle, Linnea Hemphill, Mayumi Fujita, David Norris, Preethi Ramaswamy, Jennifer Nevas, Caroline H. Rao, Allen J. Gifford, Kelly A. Asher, Adela Rambi G. Cardones, Angela F. Richardson, Carmen Adams Patrick, Louis Fiore, Ryan E. Ferguson, Soe Soe Thwin, Clara E. Kebabian, Jennifer Pavao, Mike Sather, Carol Fye, David Hunt, Leslie Robinson-Bostom, Gladys Telang, Caroline Wilkel, Harley A. Haynes, Maurice Alan Brookhart, Eliot N. Mostow, Thomas Rector

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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.

Original languageEnglish (US)
Pages (from-to)952-960
Number of pages9
JournalJAMA Dermatology
Volume151
Issue number9
DOIs
StatePublished - Sep 1 2015

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ASJC Scopus subject areas

  • Dermatology

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Pomerantz, H., Hogan, D., Eilers, D., Swetter, S. M., Chen, S. C., Jacob, S. E., Warshaw, E. M., Stricklin, G., Dellavalle, R. P., Sidhu-Malik, N., Konnikov, N., Werth, V. P., Keri, J., Lew, R., Weinstock, M. A., Marcolivio, K., DiGiovanna, J. J., Ferguson, R., Ringer, R., ... Rector, T. (2015). Long-term efficacy of topical fluorouracil cream, 5%, for treating actinic keratosis: A randomized clinical trial. JAMA Dermatology, 151(9), 952-960. https://doi.org/10.1001/jamadermatol.2015.0502