POLYPHARMACY AND CANCER: А NEW VISION FOR SKIN CANCER PATHOGENESIS-PHOTOTOXICITY AND PHOTOCARCINOGENICITY DUE TO NITROSAMINE CONTAMINATION DURING TELMISARTAN/ TAMSULOSIN INTAKE.

Abstract

The toxicokinetics of nitrosamines remain a mystery to this day, though it appears that the role of nitrosamines in potentiating the generation of mutations required for the onset of skin cancer continues to be a significant concern. Nitrosamines are mutagens, genotoxic substances, and mediators of phototoxicity/carcinogenicity, whose long-term daily usage, in the context of polypharmacy, can result in the parallel appearance of heterogeneous forms of skin cancer: keratinocytic and melanocytic. But a number of clinical observations suggest that it is the nitrosamines that potentiate the multiple occurrences of skin cancer over the years, or recurrences of skin cancer localized in areas exposed to solar radiation. This article reports the occurrences of keratoacanthoma and multiple actinic keratoses in a patient on systemic therapy with telmisartan and tamsulosin - medications that contain Nitrosamines/ NDSRIs. Successful surgical treatment by modificated advancement flap and cryotherapy was performed. The role of nitrosamines as mediators of phototoxicity in the context of drug-mediated Photo-Nitrosogenesis/ Nitrosocarcinogenesis is discussed. Contamination of certain classes of drugs with nitrosamines is proving to be more than a serious problem. This problem is fueled on the one hand by the fact that nitrosamines are 1) photocarcinogens (known for decades), but on the other hand, they are also 2) mutagens/carcinogens, genotoxic substances (according to the FDA classification). The phototoxic effect according to current data is not calculated by the tests provided by the regulators (at least so far), which in practice leads to a miscalculation of the total, cumulative carcinogenic effect in the context of the intake of a contaminated mono or polymedication. The tests could be seen as either largely static, according to some clinical observations-even as categorically insufficient in terms of defining the concept of carcinogenicity in real-world settings (such as the intake of carcinogens with drugs, for example). The processes of carcinogenesis are dynamic, multifactorial and could hardly be characterized by this kind of tests. New literature evidence finds a disconnect precisely in the determination of carcinogenic activity by assays proposed by regulators such as the Ames test (in bacteria) and the CPCA test in rodents. An open dilemma remains: since there is no concordance between the mutagenicity test in bacteria (Ames) with that in rodents (CPCA), what should be their significance in humans? For this reason, the application of the above-mentioned tests might be seriously limited in the future. We present a patient with multiple actinic keratoses and an epithelial skin tumor in the scalp area that developed during therapy with Tamsulosin and Telmisartan. We comment on the role of drug-mediated Photo-Nitrosocarcinogenesis/Oncopharmacogenesis in the background of potential/actual carcinogen contamination.