Intralesional 5-Fluorouracil for Treatment of Non-Melanoma Skin Cancer: A Systematic Review

February 2021 | Volume 20 | Issue 2 | Original Article | 192 | Copyright © February 2021


Published online January 22, 2021

Jalal Maghfour MSa, Drew Kuraitis MD PhDb, Andrea Murina MDb

aSchool of Medicine, Tulane University School of Medicine, New Orleans, LA
bTulane University Department of Dermatology, New Orleans, LA

Abstract
Background: Surgical excision is the paradigm treatment option for non-melanoma skin cancer (NMSC), however intralesional fluorouracil (IL 5-FU) is an efficacious alternative and superior to other chemotherapy agents in NMSC. Yet, little summative data exists on the topic.
Objective: To assess the efficacy of IL 5-FU in the treatment of NMSC.
Methods and Materials: A systematic review was performed using PubMed, Embase and Web of Science databases. 19 studies were included. ANOVA test was used to compare the duration of lesion prior to therapy and resolution time following IL 5-FU treatment. A two-way proportion test was performed to compare the clearance rate between squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and keratoacanthoma (KA).
Results: There was no significant difference between the clearance rate of SCC and BCC after IL 5-FU therapy (87 % vs 91.4%, respectively; P=0.2); however, the clearance rate of both SCC and BCC was significantly greater than that of KA (74.5%; P<0.007); 95% CI [2.56%–19.1%]. Lesion duration and resolution time did not significantly differ across SCC, BCC, and KA (P>0.3).
Conclusion: While majority of data is derived from individual cases, IL 5-FU achieved higher clearance rate in SCC and BCC groups than in KA group.

J Drugs Dermatol. 20(2):192-198. doi:10.36849/JDD.2021.5518

INTRODUCTION

Non-melanoma skin cancer (NMSC) is the most common cancer in the United States, with an estimated 3 million individuals affected in 2012.1-3 Management strategies for NMSC include electrodessication & curettage, wide local excision, Mohs micrographic surgery (MMS).4-8 Surgical excision remains the gold standard, with MMS offering one the highest cure and lowest recurrence rate.9

Although cost is not the single factor that determines treatment type, the average cost for treatment with excision and MMS are $1,222 and $2,085, respectively.10 It is important to consider alternative therapies that are cost-effective, especially for patients who are poor surgical candidates.11,12 Non-surgical treatments commonly used in management of NMSC include topical imiquimod and topical 5-fluorouracil (5-FU).13 These agents are effective in the treatment of the superficial variant of basal cell carinoma (BCC) and have been approved by the US Food and Drug Administration (FDA).14 Intralesional therapy using chemotherapeutics such as 5-fluorouracil and bleomycin have been routinely used to treat NMSC, however, there are no guidelines for the use of intralesional therapy for NMSC.15,16 In contrast to MMS, IL 5-FU is an inexpensive regimen; the cost of a 50 ml vial of IL 5-FU ranges from $19.50–$26.00.16 We performed a systematic review investigating the efficacy of IL 5-FU as a monotherapy in the treatment of squamous cell carcinoma (SCC), keratoacanthoma (KA), and BCC.

METHODS

A comprehensive systematic review was performed using PubMed/Medline, Embase and Web of Science databases. The search included the following terms: “Keratinocyte Carcinoma”, “cutaneous, squamous cell” or “Basal cell carcinoma”, “keratoacanthoma” or “SCC-KA type” or “Bowen’s disease”, “SCC In Situ” in combination with “Intralesional”, “Intradermal”, “5-Flurouracil”, “5FU”.

We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.18 Studies were searched from inception to February 2020.

125 studies were identified using the search terms. Full-text articles reporting IL 5-FU for the treatment of SCC, BCC and KA with reported outcome measures were included. There were no geographical or language restrictions. The following study types were excluded: 1) studies using oral systemic and/or topical agents in combination; 2) studies with patients on systemic chemotherapeutics known to induce keratinocyte carcinomas (ie, epidermal-growth factor receptor inhibitors); 3) studies that used adjunct radiotherapy.

125 articles were reviewed by at least two authors (JM, DK) and were screened by title and abstract; of 125 articles, 28 were eligible for full text review. 19 studies met the inclusion criteria and nine studies were excluded.19-27