PpIX fluorescence kinetics and increased skin damage after intracutaneous injection of 5-aminolevulinic acid and repeated illumination.

Photodynamic therapy with topically applied 5-aminolevulinic acid is used successfully for superficial skin lesions. The results for thicker, nodular lesions are less favorable. The method of aminolevulinic acid administration, the concentrations of aminolevulinic acid, and the irradiation schemes used so far have not been investigated thoroughly. As aminolevulinic acid photodynamic therapy has high potential for the increasing problem of skin cancer, we investigated both visually and histopathologically the photodynamic-therapy-induced skin damage after intracutaneous administration of aminolevulinic acid in normal porcine skin. We also investigated the kinetics of the aminolevulinic-acid-induced photosensitizer protoporphyrin IX fluorescence after irradiation in relation to fluence and irradiance. Finally we investigated the effect on photodynamic-therapy-induced damage of a fractionated irradiation. This study demonstrates that intracutaneous administration of aminolevulinic acid leads to higher fluorescence levels and thus to formation of higher protoporphyrin IX concentrations than topical application of aminolevulinic acid cream. The peak level of protoporphyrin IX after intracutaneous administration of aminolevulinic acid is reached earlier than after topical administration. The comeback of fluorescence, indicating re-synthesis of protoporphyrin IX after irradiation, is inhibited with increasing fluence. Photodynamic-therapy-induced damage increases with increasing fluence, but is independent of the irradiance. Finally, the photodynamic-therapy-induced skin damage seems to be greater after fractionated irradiations with two equal light fractions of 15 J per cm2 separated by a dark interval of 2 h.

Consensus-based evaluation of clinical significance and management of anticancer drug interactions.

BACKGROUND: Anticancer drug interactions can affect the efficacy and toxicity of anticancer treatment and that of the interacting drugs. However, information on the significance, prevention, and management of these interactions is currently lacking. OBJECTIVE: The purpose of this study was to assess the clinical significance of interaction among anticancer agents and comedications and to provide recommendations for the management of clinically significant interactions. METHODS: Members of a multidisciplinary expert group of hospital and community pharmacists, medical oncologists, internists, and clinical pharmacologists were selected by their professional organizations, which participated in this consensus project. Literature was extensively searched for any drug interactions with anticancer agents using registration files, reference books, handbooks, and electronic databases. Interactions between anticancer agents were not considered. Interactions were classified by level of best available evidence for the interaction and by severity of the clinical effect, according to a structured assessment procedure. This assessment distinguished 5 levels for the amount and quality of evidence available and 6 severity levels for classification of potential drug-to-drug interactions. RESULTS: A total of 88 drug interactions with anticancer agents were identified from 146 combinations of drugs with anticancer agents found in literature. For 58 combinations, there was insufficient evidence of an interaction. Of the identified interactions, 38 were classified as clinically significant, defined as necessitating an alert or intervention, such as dose adaptation, comedication, discontinuation of treatment, or additional monitoring of treatment. Recommendations were made for management of these interactions. CONCLUSION: Numerous interactions with anticancer agents are clinically significant and should be considered by pharmacists and doctors in daily oncology practice.