Patient-Oriented Evidence That Matters

5% Fluorouracil Is the Preferred Treatment for Actinic Keratoses


Am Fam Physician. 2019 Aug 15;100(4):249-250.

Clinical Question

What is the best approach to treat multiple actinic keratoses in a single field?

Bottom Line

The use of topical 5% fluorouracil is most likely to result in successful elimination of actinic keratoses in a field on the head or face. Treatment is once weekly for four weeks, which may create a barrier to adherence for some patients (even in this trial, where adherence should be optimal, 12% of patients were nonadherent). The impact of treatment on longer term outcomes, such as progression to squamous cell carcinoma, is not reported in this one-year study. (Level of Evidence = 1b)


The best field treatment for actinic keratoses (treatment of multiple lesions in a single continuous field) has not been established. Investigators recruited 1,174 patients from four Dutch dermatology clinics, of whom 624 met eligibility criteria (at least five actinic keratoses in a 25-cm to 100-cm contiguous area of the head or neck). The median age of participants was 73 years, 89% were men, and approximately half the lesions were on the face with the other half on the top of the head or vertex. The patients were randomized to receive one of four treatments: fluorouracil, imiquimod (Aldara), ingenol mebutate (Picato), or methyl aminolevulinate (Metvixia) with photodynamic therapy. Patients in the imiquimod group were evaluated at one month and were retreated if they were classified as a treatment failure (less than 75% lesion response). This retreatment of treatment failure was also done for the other three treatment groups at three months. Those who failed a second course of treatment were classified as treatment failures for the final assessment of outcomes, which occurred at 12 months. Only two to five patients in each group withdrew. A modified intention-to-treat analysis found that fluorouracil had the best results, with a cumulative success rate of 75% (compared with 54% for imiquimod, 38% for methyl aminolevulinate with photodynamic therapy, and only 29% for ingenol mebutate). The per-protocol analysis had similar findings, as did an analysis of patients limited to grade I or II actinic keratoses. Adverse events were common and similar across groups, with early severe burning pain much more common among those undergoing methyl aminolevulinate with photo-dynamic therapy. U.S. pricing based on GoodRx (http://www.goodrx.com, April 12, 2019) was $83 for fluorouracil, $23 for imiquimod, and $1,037 for ingenol mebutate.

Study design: Randomized controlled trial (single-blinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (specialty)

Reference: Jansen MH, Kessels JP, Nelemans PJ, et al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med. 2019;380(10):935–946.

Editor's Note: Dr. Ebell is Deputy Editor for Evidence-Based Medicine for AFP and cofounder and Editor-in-Chief of Essential Evidence Plus, published by Wiley-Blackwell. Dr. Shaughnessy is an Assistant Medical Editor for AFP.


POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see http://www.essentialevidenceplus.com. Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see http://www.essentialevidenceplus.com/product/ebm_loe.cfm?show=oxford.

To subscribe to a free podcast of these and other POEMs that appear in AFP, search in iTunes for “POEM of the Week” or go to http://goo.gl/3niWXb.

This series is coordinated by Sumi Sexton, MD, Editor-in-Chief.

A collection of POEMs published in AFP is available at https://www.aafp.org/afp/poems.



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