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

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