Keratinocyte Carcinoma Chemoprevention With a Combination of Imiquimod, 5-Fluorouracil, and Tretinoin

May 2023 | Volume 22 | Issue 5 | 486 | Copyright © May 2023


Published online April 28, 2023

doi:10.36849/JDD.7334 Nahm WJ, Nichols AJ, Rapoport E, et al. Keratinocyte carcinoma chemoprevention with a combination of imiquimod, 5-fluorouracil, and tretinoin. J Drugs Dermatol. 2023;22(5):486-490. doi:10.36849/JDD.7334

William J. Nahm BAa, Anna J. Nichols MD PhDb,c, Eli Rapoport BSa, Robert S. Kirsner MD PhDb,c, Evangelos V. Badiavas MD PhDb, W. Austin Wyant MScd, Anita Arthur MD MPHe, John T. Shen MDf

aNew York University Grossman School of Medicine, New York, NY
bDr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL
cSylvester Comprehensive Cancer Center, Miami, FL
dUniversity of Miami Miller School of Medicine, Miami, FL
eDepartment of Dermatology, University of Florida College of Medicine, Gainesville, FL
fShen Dermatology, Temecula, CA

Abstract
Background: The incidence of keratinocyte carcinomas (KCs), comprising basal and squamous cell carcinomas, is rising in the United States. Chemoprevention is one modality by which patients can reduce the incidence of KCs.
Methods: We performed a retrospective review of 327 patients who employed a combination of imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream in a field therapy regimen over the face/ears or scalp for chemoprevention.
Results: Patients had dramatically lower odds of having KCs in the treatment location (face/ears or scalp) in the one-year period after field treatment than in the one-year period preceding field treatment (OR=0.06, 95% CI: [0.02, 0.15]). Patients were also at lower odds of having KCs in non-treated areas the year after field treatment than in the year preceding it (OR=0.25, 95% CI: [0.14, 0.42]). Additionally, fewer cryotherapy sessions were performed for actinic keratoses in the treatment areas in the year after treatment (mean=1.5, SD=1.21) than the year preceding treatment (mean=2.3, SD=0.99; t=11.68, P<0.001).
Conclusions: A combination of imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream were effective at reducing the incidence of new KCs for at least one year. Individualized treatment application frequency allowed for increased patient adherence. Prospective studies evaluating combination topical treatments for chemoprevention of KCs are needed to further assess the treatment effects found in this study.

J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7334

Nahm WJ, Nichols AJ, Rapoport E, et al. Keratinocyte carcinoma chemoprevention with a combination of imiquimod, 5-fluorouracil, and tretinoin. J Drugs Dermatol. 2023;22(5):486-490. doi:10.36849/JDD.7334

INTRODUCTION

Keratinocyte carcinomas (KCs), comprising basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), are the most frequently occurring human malignancies. Cure rates are high, but the incidence of KCs is on the rise in the United States.1 Correspondingly, the costs to treat these KCs are also dramatically increasing.2 In 2016, Chen et al examined the costs associated with invasive surgical treatment of skin cancer using the Medicare payment database. They reported a progressive increase in annual costs, amounting to a staggering 8.1 billion dollars in 2011.3 In addition to the costs, there is substantial morbidity when treating these KCs. Surgery remains the standard of care because of high cure rates; however, surgery can be associated with pain, bleeding, infection, scarring, and prolonged recovery.4,5 Chemoprevention is one method by which patients can reduce the incidence of malignant transformation to KCs.6 Current chemoprevention strategies include topical aminolevulinic acid and methyl aminolevulinate with photodynamic therapy (PDT),7,8 acitretin,9 isotretinoin,10 niacinamide,11 COX-2 inhibitors,12 human papillomavirus (HPV) vaccines,13 topical 5-fluorouracil,14 combinations of 5-fluorouracil and calcipotriol,15 imiquimod cream,16 tirbanibulin,17 and chemical peels.18

However, additional modalities are needed as current methods remain costly and may still be associated with significant morbidity, poor patient adherence, and ineffectiveness. Examples include PDT,8 systemic retinoids,19 and oral COX-2 inhibitors.20-22 One study showed a 2 to 4 week course of topical 5-fluorouracil 5% cream applied to the face and ears was found