Actikerall™ (5-Fluorouracil 0.5% and Salicylic Acid 10%) Topical Solution for Patient-directed Treatment of Actinic Keratoses

Harrison P. Nguyen, BA; Jason K. Rivers, MD, FRCPC, FAAD


Skin Therapy Letter. 2016;21(3) 

In This Article

Evidence From Clinical Trials

The primary evidence used to support the efficacy of 5-FU-SA in the treatment of AKs comes from a single randomized, multi- center, phase III trial.[14] The study included 470 patients with histologically diagnosed AK on the face, forehead, or bald scalp. Subjects were randomly assigned to 5-FU-SA, diclofenac 3% gel in hyaluronic acid (diclofenac HA), or placebo (5-FU-SA vehicle) and treatment was continued until complete resolution of the lesions, or for a maximum of 12 weeks. Subjects were instructed to apply their assigned intervention directly to the lesions - once daily for the 5-FU-SA and vehicle groups, and twice daily for the diclofenac group. The primary outcome - histological clearance of one defined lesion within 8 weeks of treatment cessation - was achieved in 72.0%, 59.1%, and 44.8% of patients treated with low- dose 5-FU-SA, diclofenac and placebo, respectively. Of note, up to 25% of untreated AKs may regress spontaneously over a 1 year period,[15] and therefore, this phenomenon does not fully explain the high rate of clearance noted in the aforementioned study's placebo group.

In addition to the histological data, the rate of complete clinical clearance was also highest in the study group (55.4% vs. 32.0% and 15.1% for 5-FU-SA, diclofenac HA, and vehicle groups, respectively).[14] Similar to the temporary lesion increase associated with other topical therapies, an ephemeral increase in mean lesion area was observed only in patients treated with 5-FU-SA at week 2. However, by the end of the treatment period, reduction in mean lesion area was more evident in the study medication group compared to the comparator and placebo groups (355.9 mm2, 345.7 mm2, and 341.4 mm2, respectively). In a more recent non- interventional study, the reduction in number and size of AKs after 0.5% 5-FU-SA therapy was observed even after a short period of use: target results were achieved in approximately half of patients within 6 weeks of treatment commencement.[16]

Another study assessed the efficacy of low-dose 5-FU-SA versus cryosurgery in patients with grade II/III hyperkeratotic AKs.[17] In this open labelled, randomized trial, patients with histologically con rmed AK received either a 6-week course of once daily topical 5-FU-SA applied directly to lesions or up to two cryosurgical treatments spaced 3 weeks apart. Although the sample size (33 per treatment arm) was not powered to draw statistically significant conclusions, 5-FU-SA achieved greater histological clearance as measured by mean lesion area and lower recurrence of lesions compared to cryosurgery at the 6-month follow-up.

Non-invasive assessment using reflectance confocal microscopy and high-definition optical coherence tomography has provided insight into the in vivo pharmacodynamic changes induced by 5-FU-SA. In one study, AKs were assessed 2 weeks after the last treatment with 5-FU-SA, and the measurement of stratum corneum and epidermis thickness showed significant reduction in both clinical and subclinical lesions.[18] Moreover, histological characteristics of AK - including scaling, detached corneocytes, atypical honeycombing, round nucleated cells in the spinosum granulosum, round vessels, and inflammatory cells were all markedly reduced in lesions treated with 5-FU-SA.[18]

Unlike 5-FU alone, there have been no studies to assess 5-FU- SA's ability to treat superficial basal cell carcinoma or Bowen's disease.[19]