Results of an Investigator-Initiated Single-Blind Split-Face Comparison of Photodynamic Therapy and 5% Imiquimod Cream for the Treatment of Actinic Keratoses

McKay-Dee Dermatology, Ogden, Utah, USA.
Dermatologic Surgery (Impact Factor: 2.11). 02/2012; 38(5):722-7. DOI: 10.1111/j.1524-4725.2012.02340.x
Source: PubMed


Topical photodynamic therapy (PDT) with aminolevulinic acid (ALA) and 5% imiquimod cream are effective therapies for the treatment of actinic keratoses (AKs), but no split-face studies directly comparing these treatment options are available in the literature.
To compare the efficacy and tolerability of ALA-PDT and imiquimod 5% cream for the treatment of AKs.
Sixty-one patients were enrolled from the Salt Lake City Veterans Affairs Hospital; 51 completed the study and were included in the analysis. All patients were randomized to receive half of a sachet of imiquimod 5% cream twice weekly on half of their face and two sessions of PDT with 20% solution of ALA applied for 1 hour to the other side of the face. The 75% AK clearance rate was 34.6% for ALA-PDT and 25% for imiquimod 5% cream (p = .30). The mean reduction in AK count was 59.2% for ALA-PDT and 41.4% for imiquimod 5% cream (p = .002). Dermatology Life Quality Index (DLQI) scores were assessed for each treatment modality at week 4 and were 1.95 and 1.38, respectively (p = .20).
The sample size was small, and patients applied a small amount of imiquimod 5% cream (half a sachet) to a large surface area.
There was no statistically significant difference in treatment response when the 100% or 75% clearance rate cutoff was used, but our secondary outcome suggests that two sessions of ALA-PDT is superior to imiquimod 5% cream for the treatment of AKs. There was no statistically significant difference in effect on quality of life as assessed using the DLQI.

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    • "In a randomized trial comparing imiquimod against cryotherapy in the treatment of AK over a 12-month period, it was found that repeated cryotherapy (up to 4 sessions) achieved a higher complete lesion clearance rate (85% vs. 66.9%), while cosmetic outcome was better with imiquimod (likely related to lower incidence of hypopigmentation) [82]. In another split-face study comparing imiquimod against PDT, the authors found that there was no significant difference in 100% or 75% response to either treatment regimen, but mean lesion reduction rate was superior in the PDT group [83]. "
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    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.
    03/2014; 4(1). DOI:10.1007/s13555-014-0049-y
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    ABSTRACT: Introduction: Actinic keratosis (AK) represents the initial intraepidermal manifestation of abnormal keratinocyte proliferation, with the potential of progression to squamous cell carcinoma (SCC). Few visible AKs lead to the use of lesion-directed treatments, including ablative and/or surgical procedures. Multiple and/or the suspicion of subclinical (non-visible) AKs lead to the use of field-directed therapies, including topical and ablative treatments. Predicting which AK will progress to SCC is difficult, and so all are treated. The goals of treatment are to eliminate visible AKs and to treat subclinical (non-visible) AKs, minimizing their risk of progression to invasive SCC, while pursuing good cosmesis. Areas covered: This review discusses the prevention of AKs (such as ultraviolet light avoidance, sunscreen use, protective clothing, and frequent self-examinations, in addition to chemoprevention with retinoids, eflornithine, silymarin, and others). It also covers lesion-directed treatments (e.g., cryotherapy, electrodessication and curettage, and surgery). Field-directed treatments are also mentioned (including laser resurfacing, dermabrasion, chemical peels, topical immunomodulators (imiquimod and diclofenac), topical chemotherapeutic agents (5-fluorouracil and retinoids), and photodynamic therapy). Finally, newer and investigational treatments are discussed (including ingenol mebutate). Expert opinion: There is no panacea in the treatment of AKs. The current best approach is the sequential treatment with a lesion-directed and a field-directed therapy. Several combinations seem to work well; they just need to be selected based on the evidence and adjusted to patient needs, preferences and dermatologist expertise.
    Expert Opinion on Pharmacotherapy 09/2012; 13(13):1847-71. DOI:10.1517/14656566.2012.716039 · 3.53 Impact Factor
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    ABSTRACT: An exponentially increasing incidence, malignant potential and economical interest have made actinic keratoses (AKs) a strategic healthcare issue. The debate whether AKs are precursor lesions or in situ cancers with a continuum towards invasive squamous cell carcinoma has faded, given the millions of affected individuals. Cumulative exposure to ultraviolet light and increasing life expectancy, together with an over-aged, therefore increasingly affected population, create responsibilities for clinicians. Guidelines in the UK (2007) and Europe (2011), meta-analyses and overviews of selected treatment options, as well as some selected combined treatment strategies, are available. No comprehensive overview providing explicit details of randomized studies, including the majority of approved and popular treatment options, and designating evidence-based criteria has been published so far, a goal desirable to avoid a biased perspective on therapeutic approaches. This review defines the state of art for destructive and topical treatment options based on randomized trials which meet criteria like >30 patients in an intention-to-treat analysis, an easily reproducible study design with responses rated towards treatment as the major objective, measured as complete remission. Epidemiological data include grades and location of treated AKs, operational procedures, cryotherapy, laser therapy, 3% diclofenac in 2.5% hyaluronic acid, 2.5%, 3.75% and 5% imiquimod, 0.5% and 5% 5-fluorouracil, photodynamic therapy including ALA-patches. Sequential and combined approaches in daily practice and in developing study design might profit from the details of studies listed here. Divergent and treatment-specific proceedings, response rates after definite time intervals aiding physicians' further guidance and their management of patients are elucidated. Uncommon and new therapeutic options are discussed.
    02/2013; 23(1):14-32. DOI:10.1684/ejd.2013.1923
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