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Inflammation of actinic keratoses (AK) was originally described with systemic 5-fluorouracil, and led to the development of topical fluorouracil. Similar observations using different chemotherapeutics may point to other drugs with a potential for repositioning. This systematic review aims to evaluate chemotherapeutic agents linked to inflammation-induced cure of AK. This systematic review was registered in PROSPERO (CRD42022346168) and followed PRISMA guidelines. A comprehensive literature search for eligible original articles written in English and published in peer-reviewed journals until July 13, 2022 was conducted in MEDLINE and Embase. 28 articles met inclusion criteria accounting for 36 patients (mean age 68.4 ± 8.3 years) with inflamed AK, exposed to 21 different chemotherapeutic agents – 21/36 (58.3%) received monotherapy and 15/36 (41.7%) received multidrug combinations. Regression was complete in 13/28 (46.4%) and partial in 14/28 (50.0%) of inflamed AK. Cure rates of inflamed AK in multidrug combinations were not superior to monotherapies ( p  = .252), leading to the observation that the majority of the former (14/15; 93.3%) encompassed one of five chemotherapeutic agents linked to AK inflammation also as a monotherapy. Overall, inflammation partially/completely cured AK in 96.4% of patients (27/28). Taxanes, pemetrexed, and doxorubicin might have the potential for the management of AK.

Inflamed actinic keratoses as a biomarker in repositioning of chemotherapeutics: a systematic review and meta-analysis