METHODS
Search Strategy
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist guided this systematic review.11 A systematic search of literature available on PubMed was conducted using the search terms (((((("Fluorouracil"[Mesh]) OR "Imiquimod"[Mesh]) OR "3-ingenyl angelate" [Supplementary Concept]) OR "Diclofenac"[Mesh]) OR "tirbanibulin" [Supplementary Concept]) AND "Keratosis, Actinic''[Mesh]) AND "Randomized Controlled Trial" [Publication Type]. A search of clinical trials listed on clinicaltrials.gov was conducted using the search terms “Actinic Keratoses'' and was further filtered using the “Status - Completedâ€, “Study Results - With Results'', and “Study Phase - Phase 3†options. This initial search yielded a total of 105 articles.
Selection of Studies and Data Extraction
Articles were included into the review if they met the following criteria: (1) Actinic keratosis as the disease studied, (2) Topical, non-photosensitizing agent, (3) Phase III Clinical Trial, (4) Safety and Tolerability data reported. 92 abstracts were reviewed; 25 met the aforementioned criteria and were included in this review. Excluded abstracts were not phase III clinical trials (n=55) and studied topical photosensitizing agents (n=8). Full-text review of references in the 25 remaining abstracts as well as specific searches for phase III pivotal trial data in FDA prescribing information documents revealed 13 additional articles. A final full-text review excluded 9 articles, 6 of which were not phase III clinical trials, and 3 of which described a topical therapy which was not FDA-approved. A total of 29 articles were included. Safety and Tolerability data were extracted from each article included in the review and included the number of subjects, treatment and follow-up duration, and safety/tolerability event rate (Table 2).
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist guided this systematic review.11 A systematic search of literature available on PubMed was conducted using the search terms (((((("Fluorouracil"[Mesh]) OR "Imiquimod"[Mesh]) OR "3-ingenyl angelate" [Supplementary Concept]) OR "Diclofenac"[Mesh]) OR "tirbanibulin" [Supplementary Concept]) AND "Keratosis, Actinic''[Mesh]) AND "Randomized Controlled Trial" [Publication Type]. A search of clinical trials listed on clinicaltrials.gov was conducted using the search terms “Actinic Keratoses'' and was further filtered using the “Status - Completedâ€, “Study Results - With Results'', and “Study Phase - Phase 3†options. This initial search yielded a total of 105 articles.
Selection of Studies and Data Extraction
Articles were included into the review if they met the following criteria: (1) Actinic keratosis as the disease studied, (2) Topical, non-photosensitizing agent, (3) Phase III Clinical Trial, (4) Safety and Tolerability data reported. 92 abstracts were reviewed; 25 met the aforementioned criteria and were included in this review. Excluded abstracts were not phase III clinical trials (n=55) and studied topical photosensitizing agents (n=8). Full-text review of references in the 25 remaining abstracts as well as specific searches for phase III pivotal trial data in FDA prescribing information documents revealed 13 additional articles. A final full-text review excluded 9 articles, 6 of which were not phase III clinical trials, and 3 of which described a topical therapy which was not FDA-approved. A total of 29 articles were included. Safety and Tolerability data were extracted from each article included in the review and included the number of subjects, treatment and follow-up duration, and safety/tolerability event rate (Table 2).
RESULTS
5-Fluorouracil
5-fluorouracil (5-FU) is an antimetabolite pyrimidine analog which is incorporated into DNA and RNA by thymidylate synthase.12 Topical 5-FU preparations have been used for the treatment of AK since the 1960s9, and systematic reviews have shown it is among the most efficacious field-directed therapies for AK.13–15 Common symptoms and local skin reactions (LSRs) associated with topical 5-FU include pain, pruritus, erythema, edema, crusting, and erosion at the application site.12,16
5-fluorouracil (5-FU) is an antimetabolite pyrimidine analog which is incorporated into DNA and RNA by thymidylate synthase.12 Topical 5-FU preparations have been used for the treatment of AK since the 1960s9, and systematic reviews have shown it is among the most efficacious field-directed therapies for AK.13–15 Common symptoms and local skin reactions (LSRs) associated with topical 5-FU include pain, pruritus, erythema, edema, crusting, and erosion at the application site.12,16
