Actinic keratoses are increasingly common skin lesions that are evaluated and treated by dermatologists on a daily basis. It is estimated that more than 90% of actinic keratoses in the US are treated by destructive therapies, such as cryosurgery. The purpose of this study was to evaluate the efficacy of sequential therapy of cryosurgery followed by diclofenac sodium 3% gel.
This prospective, double-arm, multicenter, open-label, phase 4 study was performed at 82 community dermatology centers in the US. A total of 714 subjects who had a clinical diagnosis of actinic keratosis with between 5 and 15 lesions contained in a target area such as the forehead, scalp, and hands were enrolled in the study. These subjects were randomized into 2 arms of the study: cryosurgery alone and cryosurgery followed by diclofenac sodium 3% gel for a period of 90 days. Lesion counts were assessed at baseline, and 45, 75, 105, and 135 days after cryosurgery.
Of the 521 patients enrolled in the study who successfully completed all of the visits concluding on day 135, 277 were in the cryosurgery alone arm and 244 were in the cryosurgery followed by diclofenac sodium 3% gel arm. At the conclusion of the study, 46% of the subjects in the cryosurgery followed by the use of diclofenac sodium 3% gel arm achieved 100% cumulative (target plus new lesions) lesion clearance compared to 21% in the cryosurgery alone arm (P < .0001). One hundred percent target lesion clearance was achieved in 64% of the subjects in the active arm compared to 32% in the cryosurgery alone arm (P < .0001).
With the increased prevalence of actinic keratoses, it is important to consider and evaluate emerging therapeutic options. The sequential treatment with cryosurgery followed by diclofenac sodium 3% gel for 90 days is well tolerated and can provide a therapeutic modality that may provide patients with actinic keratoses a more successful outcome than monotherapy with cryosurgery by effectively treating clinical and subclinical lesions.
"Recommended dosing is twice per day for 90 days. When it is used after cryotherapy, diclofenac has been shown to give greater complete lesion clearance compared to cryosurgery alone (64% vs. 32%, respectively) . Tolerance is better than the twice daily application of 5-FU cream, but appears to be slightly less effective when used alone. "
[Show abstract][Hide abstract] ABSTRACT: Actinic keratoses (AKs) are common skin lesions heralding an increased risk of developing squamous cell carcinoma (SCC) and other skin malignancies, arising principally due to excessive ultraviolet (UV) exposure. They are predominantly found in fair-skinned individuals, and increasingly, are a problem of the immunosuppressed. AKs may regress spontaneously, remain stable or transform to invasive SCC. The risk of SCC increases for those with more than 5 AKs, and the majority of SCCs arise from AKs. The main mechanisms of AK formation are inflammation, oxidative stress, immunosuppression, impaired apoptosis, mutagenesis, dysregulation of cell growth and proliferation, and tissue remodeling. Human papilloma virus has also been implicated in the formation of some AKs. Understanding these mechanisms guides the rationale behind the current available treatments for AKs. One of the main principles underpinning the management of AKs is that of field cancerization. Wide areas of skin are exposed to increasing amounts of UV light and other environmental insults as we age. This is especially true for the head, neck and forearms. These insults do not target only the skin where individual lesions develop, but also large areas where crops of AKs may appear. The skin between lesions is exposed to the same insults and is likely to contain as-yet undetectable preclinical lesions or areas of dysplastic cells. The whole affected area is known as the ‘field’. Management is therefore divided into lesion-directed and field-directed therapies. Current therapies include lesion-directed cryotherapy and/or excision, and topical field-directed creams: 5-fluorouracil, imiquimod, diclofenac, photodynamic therapy and ingenol mebutate. Combining lesion- and field-directed therapies has yielded good results and several novel therapies are under investigation. Treatment is variable and tailored to the individual making a gold standard management algorithm difficult to design. This literature review article aims to describe the rationale behind the best available therapies for AKs in light of current understanding of pathophysiology and epidemiology. A PubMed and MEDLINE search of literature was performed between January 1, 2000 and September 18, 2013. Where appropriate, articles published prior to this have been referenced. This is not a systematic review or meta-analysis, but aims to highlight the most up to date understanding of AK disease and its management.
Electronic supplementary material
The online version of this article (doi:10.1007/s13555-014-0049-y) contains supplementary material, which is available to authorized users.
[Show abstract][Hide abstract] ABSTRACT: Patients commonly present to the otolaryngologist for management of benign facial lesions. It is important to be able to both recognize these lesions and offer patients the most effective therapies currently available. Advances in the understanding and management of three of the more common benign skin lesions affecting the face will be addressed in this review, with a particular emphasis on the most current therapeutic options for each lesion.
Actinic keratosis can now be treated with photodynamic therapy or with many topical agents, as alternatives to traditional surgical techniques. Seborrheic keratosis, as well as actinic keratosis and rosacea, are now often treated with laser therapy. In addition, rosacea management now includes nonantimicrobial topical agents, such as azelaic acid, and a wider armamentarium of systemic agents.
An understanding of these options will allow the clinician to provide patients with optimal treatment outcomes while minimizing unfavorable side effects.
Current opinion in otolaryngology & head and neck surgery 06/2009; 17(4):315-20. DOI:10.1097/MOO.0b013e32832d75e3 · 1.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Actinic keratoses are common intra-epidermal neoplasms that lie on a continuum with squamous cell carcinoma. Tightly linked to ultraviolet irradiation, they occur in areas of chronic sun exposure, and early treatment of these lesions may prevent their progression to invasive disease. A large variety of effective treatment modalities exist, and the optimal therapeutic choice is dependent on a variety of patient- and physician-associated variables. Many established and more recent approaches are discussed in this review with a focus on efficacy and administration techniques. Several previously experimental options, such as imiquimod and photodynamic therapy, have become incorporated as first-line options for the treatment of actinic keratoses, while combination treatment strategies have been gaining in popularity. The goal of all therapies is to ultimately limit the morbidity and mortality of squamous cell carcinoma. (J Clin Aesthetic Dermatol. 2009;2(7):43-48.).
Journal of Clinical and Aesthetic Dermatology 07/2009; 2(7):43-8.
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