5-AMINOLEVULINIC ACID-BASED PHOTODYNAMIC THERAPY - CLINICAL RESEARCH AND FUTURE CHALLENGES

BACKGROUND. Photodynamic therapy (PDT) for cancer patients has develop ed into an important new clinical treatment modality in the past 25 ye ars. PDT involves administration of a tumor-localizing photosensitizer or photosensitizer prodrug (5-aminolevulinic acid [ALA], a precursor in the heme biosynthetic pathway) and the subsequent activation of the photosensitizer by light. Although several photosensitizers other tha n ALA-derived protoporphyrin M. (PpIX) have been used in clinical PDT, ALA-based PDT has been the most active area of clinical PDT research during the past 5 years. Studies have shown that a higher accumulation of ALA-derived PpIX in rapidly proliferating cells may provide a biol ogic rationale for clinical use of ALA-based PDT and diagnosis. Howeve r, no review updating the clinical data has appeared so far. METHODS. A review of recently published data on clinical ALA-based PDT and diag nosis was conducted. RESULTS. Several individual studies in which pati ents with primary nonmelanoma cutaneous tumors received topical ALA-ba sed PDT have reported promising results, including outstanding cosmeti c results. However, the modality with present protocols does not, in g eneral, appear to be superior to conventional therapies with respect t o initial complete response rates and long term recurrence rates, part icularly in the treatment of nodular skin tumors. Topical ALA-PDT does have the following advantages over conventional treatments: it is non invasive; it produces excellent cosmetic results; it is well tolerated by patients; it can be used to treat multiple superficial lesions in short treatment sessions; it can be applied to patients who refuse sur gery or have pacemakers and bleeding tendency; it can be used to treat lesions in specific locations, such as the oral mucosa or the genital area; it can be used as a palliative treatment; and it can be applied repeatedly without cumulative toxicity. Topical ALA-PDT also has pote ntial as a treatment for nonneoplastic skin diseases. Systemic adminis tration of ALA does not seem to be severely toxic, but the advantage o f using this approach for PDT of superficial lesions of internal hollo w organs is still uncertain. The ALA-derived porphyrin fluorescence te chnique would be useful in the diagnosis of superficial lesions of int ernal hollow organs. CONCLUSIONS. Promising results of ALA-based clini cal PDT and diagnosis have been obtained. The modality has advantages over conventional treatments. However, some improvements need to be ma de, such as optimization of parameters of ALA-based PDT and diagnosis; increased tumor selectivity of ALA- derived PpIX; better understandin g of light light distribution in tissue; improvement of light dosimetr y procedure; and development of simpler, cheaper, and more efficient l ight delivery systems. (C) 1997 American Cancer Society.