Long‐term (6 and 12 months) follow‐up of two prospective, randomized, controlled phase III trials of photodynamic therapy with BF‐200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis

Abstract

BackgroundTwo phase III trials of photodynamic therapy (PDT) with BF-200 ALA, a recently approved nanoemulsion formulation of 5-aminolaevulinic acid (ALA) demonstrated high clearance rates in mild-to-moderate actinic keratosis (AK). The comparison to a registered methyl aminolaevulinate (MAL) cream demonstrated significantly superior total patient clearance rates.ObjectivesTo evaluate long-term efficacy and safety of PDT for AK 6 and 12 months after the last PDT with BF-200 ALA, MAL or placebo.MethodsThe follow-up phase (FUP) was performed with patients of two phase III studies. Both studies compared BF-200 ALA with placebo, one of the studies additionally with MAL. Overall recurrence rates and various subgroups (light source, lesion severity, lesion location, complete responders after first PDT) were assessed 6 and 12 months after the last PDT.ResultsRecurrence rates were similar for BF-200 ALA and MAL, with a tendency to lower recurrence rates for BF-200 ALA. The proportion of patients who were fully cleared during PDT and remained completely clear for at least 12 months after PDT were 47% for BF-200 ALA (both studies) and 36% for MAL treatment. The subgroup that was illuminated with narrow wavelength LED lamps reached 69% and 53% for BF-200 ALA (both studies, respectively) and 41% for MAL. No safety concerns were reported.ConclusionsThe FUP data confirmed the high efficacy and safety of PDT with BF-200 ALA. The slightly lower recurrence rates after BF-200 ALA treatment compared with MAL treatment enhanced the better treatment outcome due to the significantly superior efficacy.

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

“…The metaanalysis indicates that all treatment options were significantly superior compared with placebo, with BF-200 ALA photodynamic therapy being the most efficient treatment [37]. This finding is corroborated by the findings of Dirschka et al who studied and compared 1 year follow-up treatments for selected AK treatment modalities and, among those, found BF-200 ALA to show the most sustainable efficacy [39]. While all modalities are approved for lesion-directed treatment, some are additionally approved for field-directed treatment.…”

“…As referred to in the following paragraph, this improvement in penetration also results in a higher clinical efficacy of BF-200 ALA compared with an MAL preparation in mild-to-moderate AK on face and scalp [39,68].…”

“…Lesion clearance rates using placebo (narrow: 15.1%; broad: 24.6%) were clearly lower compared with verum with both illumination systems. Clinical efficacy was maintained during the follow-up periods of 6 and 12 months [39]. The probability of a subject to remain cleared 12 months after the last treatment with BF-200 ALA with narrow spectrum lamps was 67.5 or 46.8% when using all lamp types, respectively.…”

“…Moreover, in this study, efficacy was clinically assessed during follow-up visits at 6 and 12 months after the last treatment [39]. Recurrence rates after 12 months were 41.6% for BF-200 and 44.8% for MAL, depending on the light spectrum and in favor of narrow spectrum lamps.…”

Activity of phosphatase-sensitive 5-aminolevulinic acid prodrugs in cancer cell lines

“…4 Although primary employed in the treatment of dermatological conditions like actinic keratosis (AK), psoriasis, basal cell carcinoma, squamous cell carcinoma and Bowen's disease, 5-ALA has been tested for the treatment or detection of different malignancies ranging from brain tumors to lung cancer. 5,6 Today, 5-ALA has been granted marketing authorization for the treatment of AK [7][8][9][10] and the fluorescence-guided resection of malignant glioma. 4,11,12 Although showing promise for PDT and PD, 5-ALA has certain drawbacks when it comes to its physicochemical properties.…”