Fluorouracil cream most effective for treating actinic keratosis lesions
The use of 5% fluorouracil cream was most effective among a panel of four treatments commonly used for treating multiple actinic keratosis (AK) lesions on the head, according to a recent study.
This multicentre, single-blind study included 624 patients (median age 73 years) diagnosed with multiple AK lesions on the head who were randomized in a 1:1:1:1 ratio to receive 5% fluorouracil cream (n=155), 5% imiquimod cream (n=156), MAL-PDT* (n=156), or 0.015% ingenol mebutate gel (n=157) at four Dutch hospitals. Grades I–III AK lesions were assessed using a 3-point Olsen grading system. The study’s primary endpoint was the number of patients who remained free from treatment failure (defined as ≥75 percent reduction in AK lesions) at 12 months of treatment. Patients were followed up at 3 and 12 months. [N Engl J Med 2019;380:935-946]
In the modified intention-to-treat analysis, 74.7 percent of patients treated with fluorouracil cream were free from treatment failure compared with those who received imiquimod cream (53.9 percent, hazard ratio [HR], 2.03; p=0.001), MAL-PDT (37.7 percent, HR, 2.73; p<0.001), or ingenol mebutate gel at 12 months (28.9 percent, HR, 3.33; p<0.001).
In the per-protocol population comprising 555 patients, there were also significantly more patients in the fluorouracil group who were free from treatment failure (76.4 percent) than the imiquimod (56.7 percent, HR, 2.03; p=0.001), MAL-PDT (42.4 percent, HR, 2.63; p<0.001), or ingenol mebutate groups (31.8 percent, HR, 3.33; p<0.001).
Furthermore, treatment success rate was higher in the fluorouracil group than those in the imiquimod, MAL-PDT, or ingenol mebutate groups at 12 months (82.4 percent vs 71.0 percent, 49.6 percent, or 42.9 percent, respectively) in the modified intention-to-treat population.
Similar results were seen in the per-protocol analysis which showed a higher treatment success rate with fluorouracil than with imiquimod, MAL-PDT, or ingenol mebutate (82.0 percent vs 70.2 percent, 50.9 percent, or 42.4 percent, respectively).
“Findings from the modified intention-to-treat analysis and the per-protocol analysis were similar, which indicates the robustness of the results,” the researchers said.
When the modified intention-to-treat analysis was further stratified by patients with multiple grade I–III lesions, treatment success rate was higher among patients on fluorouracil than those who were received imiquimod cream, MAL-PDT, or ingenol mebutate gel (75.3 percent vs 52.6 percent, 38.7 percent, or 30.2 percent, respectively). “An important gap in the current literature is that most studies assessing the effectiveness of field-directed treatments exclude grade III AK lesions … [In our cohort, we] included patients with grade III AK lesions; in this way, it is more representative of patients seen in daily practice,” the researchers noted.
Overall, the use of fluorouracil was not associated with a higher rate of adverse events (AEs), and majority of patients reported satisfaction and sustained improvement with regard to health-related quality of life at the end of treatment. Additionally, no serious AEs were observed, and none of the patients discontinued treatment due to a drug-related AEs.
The findings were consistent with a previous network meta-analysis, which showed that 5% fluorouracil was the most effective treatment with regard to a complete clearance of all lesions, said the researchers. [Br J Dermatol 2013;169:250-259]
“However, in the 2015 European Dermatology Forum guidelines, the majority of experts did not express a preference for any of the most commonly prescribed treatments. They agreed that 3.75% imiquimod, ALA-PDT**, MAL-PDT, ingenol mebutate (0.015% or 0.050%), and 0.5% fluorouracil were equally effective in patients with multiple AK lesions,” the researchers said. [J Eur Acad Dermatol Venereol 2015;29:2069-2079]
“This trial showed that 5% fluorouracil [cream] was significantly more effective than imiquimod [cream], MAL-PDT, or ingenol mebutate [gel] at 12 months after the end of treatment for multiple [grade I–III] AK lesions in a continuous area,” said the researchers.
“No new toxic effects were identified in this trial,” they added.
*MAL-PDT: Methyl aminolevulinate photodynamic therapy
**ALA-PDT: Aminolevulinic acid photodynamic therapy