INTRODUCTION
5 - fluorouracil was identified as early as 1962 as a promising treatment for keratoacanthomas, actinic keratoses, and skin cancers.1,2 Upon entering the cell, 5-FU is converted into the active metabolites fluorodeoxyuridine monophosphate, fluorodeoxyuridine triphosphate, and fluorouridine triphosphate, which subsequently interfere with normal nucleic acid functioning resulting in targeted cell death of rapidly proliferating cells.3 5 - FU’s selective cytotoxicity and minimal effect on normal skin cells made it a promising therapeutic option that has evolved over time with demonstrated efficacy in many dermatologic conditions.4 Recently, intralesional and laser-assisted modalities of 5 - FU delivery have been described for the treatment of various disease processes with demonstrated efficacy and strong cosmetic outcomes.
METHODS
We systematically reviewed studies regarding the use of 5-FU in dermatology, including intralesional and laser-assisted modalities of delivery, according to PRISMA guidelines.5 The MEDLINE standard computer database, EMBASE computer database, and MEDLINE advanced (Internet) database were searched for articles published between January 1, 1980 and December 31, 2016.6 The following key words were used in our search: 5-fluorouracil or 5-FU alone and in combination with skin, dermatology, intralesional, intradermal, laser, laser-assisted, carcinoma, neoplasm, scar, and keloid. Journals, review articles, and references of studies found were reviewed for additional information. The following criteria were used to exclude studies from use in our systematic review: lack of objective data regarding 5-FU efficacy, language other than English, article accessibility barrier, combination therapies with three or more treatment modalities or surgery beforehand, use of an implant, duplicate studies, and emphasis outside 5-FU use in dermatologic disease. Data concerning the efficacy of 5-FU as a treatment modality, as well as the validity of each study, were then analyzed. Strength of clinical data was graded by the primary authors according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence (OCEBM, Figure 1).7 After assessing the level of evidence, studies were categorized according to method of application, and further subcategorized based on dermatologic condition treated by 5-FU.
RESULTS
In total, 87 studies were identified in the aforementioned online databases. A screening of editorials, yearbooks of dermatology, and references of studies yielded 6 additional studies for a total of 93 studies. 33 studies were excluded for reasons including lack of objective data regarding efficacy, language, article accessibility barrier, combination therapies with ≥ 3 treatment modalities or surgery beforehand, duplicate studies, and use of an implant.15
