Topical Pharmacotherapy for Actinic Keratoses in Older Adults

Abstract

Actinic keratosis is caused by excessive lifetime sun exposure. It must be treated, regardless of thickness, because it is the biologic precursor of invasive squamous cell carcinoma, a potentially deadly malignancy. Physical ablative techniques such as cryotherapy, lasers, and curettage are the most used treatments for isolated lesions. Multiple lesions are treated with topical drugs, chemical peelings, and physical techniques. Drug preparations containing diclofenac plus hyaluronate, aminolevulinic acid, and methyl aminolevulinate and different concentrations of imiquimod and 5-fluorouracil are approved for this clinical indication. All treatments have a good profile of efficacy and tolerability although there are relevant differences in the clearance rate, tolerability, and type and frequency of adverse effects. In addition, they have very different mechanisms of action and treatment protocols. No differences in the efficacy and tolerability were found in older patients compared with younger patients, therefore no dose adjustments are needed. That said, older patients often need to be motivated to treat actinic keratoses and a careful attention to expectations, needs, and preferences should be used to obtain the maximal adherence and prevent treatment failure. This goal can be achieved with a careful evaluation not only of published efficacy, toxicity, and tolerability data but also of practical topics such as the frequency of daily applications, the overall duration of therapy, and the need for a caregiver. Finally, particular attention must be paid in the case of frail patients and immunosuppressed patients.

Real-World Experience with Topical 5-Fluorouracil 4% (40 mg/g) Cream for the Treatment of Actinic Keratosis

“…Italy shows one of the highest prevalence of AK worldwide [ 2 , 3 ]. In a retrospective, observational study published in 2017, which enrolled 7,284 outpatients attending Italian general dermatology clinics, the overall mean prevalence of AK was 27.4%, with a significantly higher rate in males compared with females (34.3% versus 20.0%, respectively; P <0.001) [ 2 ].…”

“…AK is considered a precursor of invasive squamous cell carcinoma (SCC), a malignancy which can produce distant metastases [ 2 , 3 ]. The AK progression rate is highly variable (from 0.025% to 20%) and increases with the number of lesions, being 11-fold higher in patients with >20 lesions [ 1 , 4 ].…”

“…The AK progression rate is highly variable (from 0.025% to 20%) and increases with the number of lesions, being 11-fold higher in patients with >20 lesions [ 1 , 4 ]. Since it is impossible to predict lesions risk of transformation based on their morphological features, a prompt diagnosis and treatment of every AKs are essential to reduce the risk of SCC [ 2 , 3 , 5 ]. Importantly, according to the “field cancerization” (FC) concept, treatment should also target the skin surrounding AK lesions, where subclinical lesions with the potential of malignant transformation could be present [ 6 ].…”

“…5-FU is a pyrimidine analogue, which irreversibly inactivates thymidylate synthase, interfering with DNA synthesis and causing apoptosis of the high proliferative AK keratinocytes [ 1 , 8 ]. It was the first drug for AK field-directed treatment and its approval dates back to 1962 [ 3 ]. 5-FU is available for AK treatment in various formulations, with concentrations ranging from 0.5 to 5% [ 8 ].…”

“…It was the first drug for AK field-directed treatment and its approval dates back to 1962 [3]. 5-FU is available for AK treatment in various formulations, with concentrations ranging from 0.5 to 5% [8].…”