What Is the Best Field-Directed Treatment for Actinic Keratosis?


Key Points

  • 5% fluorouracil cream was the most successful treatment.
  • The probability of remaining free from treatment failure was 74.4% with fluorouracil, 53.9% with imiquimod, 37.7% with MAL-PDT, and 28.9 % with ingenol mebutate.


In a Dutch study reported in The New England Journal of Medicine, Jansen et al found that 5% fluorouracil cream was the best of four field-directed treatments for actinic keratosis, the most common premalignant skin disease in the white population.

Study Details

The study examined the effectiveness of four frequently used field-directed treatments (for multiple lesions in a continuous area). Patients from four Dutch sites with a clinical diagnosis of ≥ 5 actinic keratosis lesions on the head involving one continuous area of 25 to 100 cm2 were randomly assigned between November 2014 and March 17 to one of four treatment groups. They either received 5% fluorouracil cream (n = 155), 5% imiquimod cream (n = 156), methyl aminolevulinate photodynamic therapy (MAL-PDT; n = 156), or 0.015% ingenol mebutate gel (n = 157). The primary outcome was the proportion of patients with a reduction of ≥ 75% in the number of actinic keratosis lesions from baseline to 12 months after the end of treatment.

Successful Treatment

A modified intention-to-treat analysis was based on 602 randomly assigned patients who started treatment and for whom data regarding the primary outcome were available. At 12 months after the end of treatment, the cumulative probability of remaining free from treatment failure was 74.4% in the fluorouracil group, 53.9% in the imiquimod group (hazard ratio [HR] for failure vs fluorouracil = 2.02), 37.7% in the MAL-PDT group (HR = 2.73), and 28.9 % in the ingenol mebutate group (HR = 3.33; P ≤ .001 for all comparisons. In analysis in the per-protocol population, HRs for failure vs fluorouracil were 2.03, 2.63, and 3.33, respectively (P ≤ .001 for all comparisons).

No unexpected toxic effects were observed.

The investigators concluded, “At 12 months after the end of treatment in patients with multiple actinic keratosis lesions on the head, 5% fluorouracil cream was the most effective of four field-directed treatments.”

Disclosure: The study was funded by the Netherlands Organization for Health Research and Development. The study authors' full disclosures can be found at

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