Intralesional and Laser-Assisted 5-Fluorouracil in Dermatologic Disease: A Systematic Review
March 2018 | Volume 17 | Issue 3 | Original Article | 274 | Copyright © 2018
Garrett T. Prince BS,a Michael C. Cameron MD,a Ramin Fathi MD,b Theodore Alkousakis MDa
aDepartment of Dermatology and Cutaneous Surgery, University of Colorado School of Medicine, Aurora, CO bDepartment of Dermatology, University of Texas Southwestern Medical Center, Department of Dermatology, Dallas, TX
INTRODUCTION: 5-fluorouracil has proven to be an effective therapy in the treatment of a variety of dermatologic conditions. Approved by the United States Food and Drug Administration for the topical treatment of actinic keratoses and superficial basal cell carcinoma, 5-fluorouracil has also demonstrated efficacy in the treatment of a variety of other dermatologic diseases. While best known for its use as a topical medication, 5-fluorouracil can also be delivered intralesionally for the treatment of dermatologic disease. Recently, laser-assisted modalities for increased delivery of 5-fluorouracil have also been described METHODS: A search of the MEDLINE standard computer database, MEDLINE advanced database, and EMBASE database was conducted. RESULTS: 38 articles met criteria for inclusion in this review. These articles represented 14 randomized controlled trials and 24 case series. Each article was reviewed and summarized. The main limitation of this review is the limited number of large randomized controlled trials, as well as the non-uniformity in treatment regimens between studies. DISCUSSION: Intralesional and laser-assisted 5-fluorouracil are used in a variety of dermatologic disease processes with a wide range of efficacy and levels of evidence. Based on extent and level of evidence, our disease-specific systematic review found that the evidence is strongest for intralesional 5-FU use in the treatment of keloids, hypertrophic scars, and keratoacanthomas. This review serves as a comprehensive summary of intralesional and laser-assisted 5-fluorouracil use in dermatology.
J Drugs Dermatol. 2018;17(3):274-280.
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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.
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.
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