Actinic keratosis (AK) lesions have the potential to develop into invasive squamous cell carcinomas (SCCs), and approaches to treatment are evolving to try to reduce the burden of SCC.
Objective:
To present the published clinical research surrounding the use of 0.5% 5-fluorouracil with 10% salicylic acid (low-dose 5-FU/SA) for the treatment of hyperkeratotic AKs.
Method:
A review of published clinical evidence for low-dose 5-FU/SA for the treatment of AKs. The articles were selected following a MEDLINE database search of the combined terms fluorouracil, salicylic acid and actinic keratosis which represent the peer review publications of clinical studies that primarily investigate the use of Actikerall in AK.
Results:
Combining low-dose 5-FU with keratolytic SA is associated with high rates of histologic clearance, reduction in lesion number/area, and sustained clinical response in clinical study and the clinical practice setting. Low-dose 5-FU/SA has also been evaluated using imaging to detect the progression of subclinical AK lesions through a course of the field-directed treatment.
Conclusion:
Low-dose 5-FU/SA is an effective and well-tolerated treatment option licensed for the lesion-directed treatment of mild-to-moderate hyperkeratotic AK lesions.
Vallejo-TorresLMorrisSKingeJM. Measuring current and future cost of skin cancer in England. J Public Health (Oxf). 2014;36:140-148.
2.
HayRJJohnsNEWilliamsHC. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Invest Dermatol. 2014;134:1527-1534.
3.
GuyGPEkwuemeDU.Years of potential life lost and indirect costs of melanoma and non-melanoma skin cancer: a systematic review of the literature. Pharmacoeconomics. 2011;29:863-874.
StockflethEFerrandizCGrobJJ. Development of a treatment algorithm for actinic keratoses: a European Consensus. Eur J Dermatol. 2008;18:651-659.
6.
CriscioneVDWeinstockMANaylorMF. Actinic keratoses: natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer. 2009;115(11):2523-2530.
7.
LucasRMcMichaelTSmithW. Solar ultraviolet radiation: global burden of disease from solar ultraviolet radiation. Environmental Burden of Disease Series. No. 13. www.who.int/uv/publications/solaradgbd/en/. Accessed January 27, 2015.
8.
JonesMPFF. Dermatological effects from years in the sun: compounding opportunities. Int J Pharm Compd. 2006;10:336-342.
9.
MalvehyJ.A new vision of actinic keratosis beyond visible clinical lesions. J Eur Acad Dermatol Venereol. 2015;29(suppl 1):3-8.
10.
TraianouAUlrichMApallaZ. Risk factors for actinic keratosis in eight European centres: a case-control study. Br J Dermatol. 2012;167(suppl 2):36-42.
11.
DavisSANarahariSFeldmanSR. Top dermatologic conditions in patients of color: an analysis of nationally representative data. J Drugs Dermatol. 2012;11:466-473.
12.
SchmittJVMiotHA.Actinic keratosis: a clinical and epidemiological revision. An Bras Dermatol. 2012;87(3):425-434.
13.
Díaz-GonzálezJMPeniche-CastellanosAFierro-AriasL. Skin cancer in adults younger than 40 years at the General Hospital of Mexico. Gac Med Mex. 2011;147:17-21.
Fernandez-FiguerasMTCarratoCSaenzX. Actinic keratosis with atypical basal cells (AK I) is the most common lesion associated with invasive squamous cell carcinoma of the skin. J Eur Acad Dermatol Venereol. 2015;29(5):991-997.
16.
SlaughterDPSouthwickHWSmejkalW.Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer. 1953;6:963-968.
17.
ColomboGLChimentiSDi MatteoS. Cost-effectiveness analysis of topical treatments for actinic keratosis in the perspective of the Italian health care system. G Ital Dermatol Venereol. 2010;145:573-581.
18.
ClinicalTrials.gov. Study to evaluate the efficacy and safety of Actikerall® solution in patients with grade I-II actinic keratoses. NCT02289768. Accessed January 12, 2016.
OlsenEAAbernethyMLKulp-ShortenC. A double-blind, vehicle-controlled study evaluating masoprocol cream in the treatment of actinic keratoses on the head and neck. J Am Acad Dermatol. 1991;24:738-743.
21.
DoddsAChiaAShumackS.Actinic keratosis: rationale and management. Dermatol Ther (Heidelb). 2014;4(1):11-31.
LevySFurstKChernW.A comparison of the skin permeation of three topical 0.5% fluorouracil formulations with that of a 5% formulation. Clin Ther. 2001;23:901-907.
24.
SchlaakMSimonJC.Topical treatment of actinic keratoses with low-dose 5-fluorouracil in combination with salicylic acid—pilot study. J Dtsch Dermatol Ges. 2010;8(3):174-178.
25.
StockflethEKerlHZwingersT. Low-dose 5-fluorouracil in combination with salicylic acid as a new lesion-directed option to treat topically actinic keratoses: histological and clinical study results. Br J Dermatol. 2011;165:1101-1108.
26.
StockflethEZwingersTWillersC.Recurrence rates and patient assessed outcomes of 0.5% 5-fluorouracil in combination with salicylic acid treating actinic keratoses. Eur J Dermatol. 2012;22:370-374.
27.
SimonJCDominicusRKarlL. A prospective randomized exploratory study comparing the efficacy of once-daily topical 0.5% 5-fluorouracil in combination with 10.0% salicylic acid (5-FU/SA) vs. cryosurgery for the treatment of hyperkeratotic actinic keratosis. J Eur Acad Dermatol Venereol. 2015;29(5):881-889.
28.
SzeimiesRMDirschkaTPrechtlA. Efficacy of low-dose 5-fluorouracil/salicylic acid in actinic keratoses in relation to treatment duration. J Dtsch Dermatol Ges. 2015;13:430-438.
29.
DirschkaTLearJT.Sequential treatment of multiple actinic keratoses with solaraze and Actikerall. Case Rep Dermatol. 2014;6(2):164-168.
30.
GuptaAKPaquetMVillanuevaE. Interventions for actinic keratoses. Cochrane Database Syst Rev. 2012;12:CD004415.
31.
UlrichMMaltuschARowert-HuberJ. Actinic keratoses: non-invasive diagnosis for field cancerisation. Br J Dermatol. 2007;156(suppl 3):13-17.
32.
MalvehyJAlarconIPuigS. HD-optical coherence tomography and reflectance confocal microscopy in the monitoring of treatment of 0.5% 5-fluorouracil and 10% salicylic acid in clinical and subclinical actinic keratoses. Presented at the 1st International Symposium on Cancers of the Skin; Madrid, Spain; January 30, 2015.
33.
UlrichMAlarconIMalvehyJ. In vivo reflectance confocal microscopy characterization of field-directed 5-fluorouracil 0.5%/salicylic acid 10% in actinic keratosis. Dermatology. 2015;230:193-198.
34.
MaierTCekovicDRuzickaT. Treatment monitoring of topical ingenol mebutate in actinic keratoses with the combination of optical coherence tomography and reflectance confocal microscopy: a case series. Br J Dermatol. 2015;172:816-818.
35.
MalvehyJRoldan-MarinRIglesias-GarciaP. Monitoring treatment of field cancerisation with 3% diclofenac sodium 2.5% hyaluronic acid by reflectance confocal microscopy: a histologic correlation. Acta Derm Venereol. 2015;95:45-50.
