Randomized, Vehicle-controlled Trials of Topical 5-fluorouracil Therapy for Actinic Keratosis Treatment

An Overview

Maral Rahvar; Sonia A Lamel; Howard I Maibach


Immunotherapy. 2012;4(9):939-945. 

In This Article

Abstract and Introduction


Actinic keratoses are common in older individuals and topical immunotherapy is an important treatment when multiple lesions are present. To assess the efficacy of 5-fluorouracil in treating actinic keratoses, a systematic review of randomized, vehicle-controlled trials was performed. Percentages of 5-fluorouracil and vehicle responders were determined by absolute clearance and mean percent reduction in lesion count. Four trials with 399 and 269 participants in active treatment and vehicle groups, respectively, were evaluated. After 4 weeks of treatment, total clearance and mean lesion count reduction were 52.6 and 90.2% in the treatment group versus 0.85 and 28.3% in the vehicle group, respectively. Topical 5-fluorouracil is efficacious in treating actinic keratoses; however, vehicle responses warrant further investigation of study design and disease severity scales.


Actinic keratosis (AK), or solar keratosis, is a common disease in fair-skinned, older individuals.[1] This intraepidermal precancerous lesion often affects skin chronically exposed to UV radiation such as on the face, scalp, ears, arms, and dorsum of the hands.[2–4] These lesions have the potential to regress or remain unchanged, but without treatment it has been suggested that 0.25–16% of cases transform into squamous cell carcinoma (SCC).[5–9]

While the prevalence of AKs varies in different populations, AKs were diagnosed at 47 million office visits and 14% of visits to the dermatologist, according to National Ambulatory Medical Care Survey data from 1990 to 1999.[10] As the National Ambulatory Medical Care Survey only accounts for outpatient visits, this value underestimates the actual prevalence, missing AKs present in the medically underserved and patients seen in other care settings.[11] The incidence of AKs is age dependent, affecting approximately 10% of patients in their 20s and 80% of those 70 years of age and older.[12,13]

Clinically, AKs are identified as scaly reddish-brown-colored macules or papules on an erythematous base, with surrounding areas of skin potentially exhibiting signs of sun damage such as telangiectasia, actinic collagenosis or dyschromia.[6,14] Because of the rough texture of AKs, early lesions are often more amenable to discovery by palpation.[15] The differentiation between an AK and SCC is not always clinically possible and no clinical feature can reliably predict malignant progression; however, characteristics such as increased erythema, thickening, ulceration, induration and growth may indicate transformation to SCC.[2,16] Therefore, treatment of all AKs may be warranted to reduce morbidity and mortality.[17,18]