Topical Aminolevulinic Acid HCL

Abstract

Phase III testing of aminolevulinic acid (ALA) in topical photodynamic therapy (PDT) has resulted in US Federal Drug Administration approval of the treatment for actinic keratosis on face and scalp. A 20% ALA solution (Levulan®, KerastickTM ) is applied by a specially designed dermal applicator to the skin for 14 to 18 hours before exposure to blue light of wavelength 417nm (exposure time 1000 seconds; light dose, 10 J/cm2). ALA preferentially penetrates the abnormal stratum corneum of diseased skin, localizes in dysplastic and neoplastic tissue and leads to extensive endogenous protoporphyrin IX (PpIX) production in cells. Subsequent activation of PpIX by visible light destroys cells by the production of cytotoxic reactive oxygen species. In the phase III study, 1 or 2 exposures to ALA PDT cleared 72% of actinic keratoses on face and scalp as assessed 12 weeks after the initial treatment. Importantly, previous studies had revealed that actinic keratoses on the face and scalp responded significantly better to ALA-PDT than lesions on other body sites.[1,2] The adverse event profile of ALA PDT seems to be favourable. The major short term adverse effects are burning and stinging during PDT and transient localized erythema and edema after PDT. In contrast to other forms of PDT, systemic photosensitization and/or phototoxic reactions at distant sites do not occur in the setting of topical ALA PDT. Treatment of actinic keratoses is necessary because these lesions are potential precursors of squamous cell carcinoma. The standard armamentarium of treatments includes curettage and electrodesiccation, C02 laser ablation, cryosurgery, topical chemotherapy with fluorouracil (5FU) and now ALA PDT. The choice of treatment modality depends not only on the location, size and extent of lesion(s), but also on the physician’s and patient’s experience with the therapeutic technique. ALA PDT seems to be particularly useful in the treatment of multiple and widespread actinic keratoses which has previously been the domain of 5FU treatment. In contrast to 5FU, which has to be applied daily for, on average, up to 10 to 12 weeks and often induces strong inflammatory reactions at exposure sites, the reaction to ALA PDT is usually moderate and short lasting. However, the real clinical value of ALA PDT will be upheld by the long term disease-free rates after treatment and ultimately by patients’ acceptance of this treatment. In these aspects, our results[1] and those of other investigators promise ALA PDT a bright future in the treatment of actinic keratoses. ▲