Phototoxic reactions in healthy volunteers following photodynamic therapy with methylaminolevulinate cream or with cream containing 5‐aminolevulinic acid: a phase II, randomized study

Background: Photodynamic therapy (PDT) is the selective destruction of abnormal cells through activation of a photosensitizer in the presence of oxygen. Local phototoxic reactions and pain are the most common limiting side effects. Purpose: The primary objective was to compare the local phototoxic response following PDT with methylaminolevulinate (MAL) and 5‐aminolevulinic acid (ALA). The secondary objectives were to compare the two treatments regarding pain, detection of substance P, change in fluorescence intensity from before to 5 h after cream application and adverse events not related to local phototoxicity. Methods: Thirty‐four healthy volunteers were treated by PDT using MAL 160 mg/g cream and ALA cream 20% randomly assigned to treatment areas on the inside of each upper arm. A composite score of local phototoxic events (erythema, edema, hyperpigmentation) was calculated. Results: The area under the curve (AUC) analysis of composite scores showed a significantly higher AUC for ALA‐PDT ( P ≤0.0001). ALA‐ and MAL‐PDT showed equivalent local side‐effect frequencies, except for a higher frequency of hyperpigmentation after 28 d using ALA‐PDT ( P =0.006). Conclusion: MAL‐ and ALA‐PDT are nearly equivalent regarding individual side‐effect frequencies, but MAL‐PDT has a more favorable phototoxicity pattern as seen by AUC analysis and the lower frequency of long‐lasting hyperpigmentation.