Fluorouracil cream topped other therapies for treating actinic keratosis lesions on the head in a single-blind, randomized trial.
Treatment success was significantly greater among the fluorouracil group at 1 year follow up as the overall probability of staying free from treatment failure was 74.7% (95% CI 66.8%-81.0%) versus 28.9% to 53.9% for three other common treatments, reported Maud Jansen, MD, of Maastricht University Medical Center in the Netherlands, and colleagues in the New England Journal of Medicine.
For those other remedies, the investigators found probabilities of remaining free from treatment failure as follows:
- 28.9% (95% CI 21.8 to 36.3) for ingenol mebutate
- 53.9% (95% CI 45.4 to 61.6) for imiquimod
- 37.7% (95% CI 30.0 to 45.3) for methyl aminolevulinate photodynamic therapy (MAL-PDT)
Moreover, hazard ratios for treatment failure were 2.73 (95% CI 1.87-3.99) for MAL-PDT, 3.33 (95% CI 2.29-4.85) for ingenol mebutate, and 2.03 (95% CI 1.36-3.04) for imiquimod when compared with fluorouracil.
Treatment failure was considered to be less than a 75% decline from baseline in actinic keratosis lesion counts. It could be determined 1 year following the first successful treatment or at 3 months following the final treatment.
Primary care providers and dermatologists often encounter actinic keratosis lesions in their practice. As the age of the general population increases so does the incidence of actinic keratosis, placing a substantial burden on the healthcare system, noted Jansen’s group.
Field-directed treatments are generally preferred because they may have a prophylactic effect for preventing new lesions from forming, while also treating existing actinic keratosis, Jansen and colleagues explained. Field-directed therapies may also be beneficial in preventing the development of squamous-cell carcinoma.
However, existing guidelines provide no clear recommendation regarding which treatment is optimal. Hence, treatment is often based on (often subjective) preferences of the physician and/or the patient. There is limited evidence from randomized trials directly comparing long-term follow up and treatment, the researchers emphasized.
“Our results could affect treatment choices in both dermatology and primary care. From a cost perspective, fluorouracil is also the most attractive option. It is expected that a substantial cost reduction could be achieved with more uniformity in care and the choice for effective therapy,” the researchers wrote.
The researchers evaluated 624 patients with a median age of 73 at four Dutch hospitals. Participants were randomized 1:1:1:1 to ingenol mebutate, fluorouracil, MAL-PDT, and imiquimod. High percentages of patients in all groups were fully adherent to their assigned treatments.
Jansen’s group assessed the effectiveness of four common field-directed therapies used to treat multiple lesions. Among the inclusion criteria were clinical diagnosis with ≥5 actinic keratosis lesions on the head, including one continuous region of 25-100 cm2.
Adverse events were seen among 92.6% of the fluorouracil group, 85.1% of the imiquimod group, 96.6% of the MAL-PDT group, and 95.7% of the ingenol mebutate group. Most of these were cosmetic (e.g., erythema, crusting, scaling), but itching was common with all treatments. Severe pain or burning sensations occurred during treatment in more than half of MAL-PDT patients versus about 10% of those assigned to fluorouracil. When assessed again 2 weeks after treatment ended, these symptoms were severe in 5%-6% of the fluorouracil group and 10%-13% of those receiving MAL-PDT.
The greatest increase in health-related quality of life and patient satisfaction with treatment were found among fluorouracil patients. For example, 86% of the fluorouracil group said they would willingly undergo retreatment if necessary, compared with 60% to 76% of the other groups.
Good-to-excellent cosmetic results were found among 89.7% of the imiquimod group, 90.3% of the fluorouracil group, 96.6% of the MAL-PDT group, and 95.1% of the ingenol mebutate group.
The study was funded by the Netherlands Organization for Health Research and Development.
Jansen disclosed relationships with Galderma.