Article

A Single-Arm, Open-Label, Phase IV Study to Evaluate the Efficacy of a Topical Formulation for Hyperkeratotic Actinic Keratosis Lesions

Authors:
  • Giuliani, Milan, Italy
  • International Hair Research Foundation
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Abstract

Introduction: Actinic keratosis (AKs) are epidermal lesions that commonly occur in skin exposed to chronic cumulative UV irradiation. Untreated AK lesions can advance to squamous cell carcinoma. Current treatments of AK have many shortcomings; for instance, not all treatments can be used for the hyperkeratotic form of AK. The aim of this study was to test the efficacy and tolerability of a topical product containing 2,4,6-octatrienoic acid and urea for the treatment of hyperkeratotic AK lesions. Methods: Forty male and female subjects with at least two hyperkeratotic AK lesions were enrolled in this single-arm, open-label phase IV study. The product was applied twice daily for two consecutive months. The efficacy endpoints were the reductions in the mean number of AK lesions per subject from baseline (T0) to the end of the trial (T1) and to three months after the end of the treatment period (T2). Results: At T0, the mean (SD) number of lesions per subject was 3.65 (1.25). At the end of the treatment period (T1), this number had dropped (significantly, p < 0.0001) by 83.56%. The mean number of lesions per subject then decreased by 41.47% (p < 0.0001) between T1 and the three-month follow-up visit (T2). Complete elimination of lesions had occurred in 57.5% of the subjects at T1, and 82.5% (55% who had remained completely clear of lesions since T1, and 27.5% who had fully eliminated their lesions during the period from T1 to T2) at T2. No side effects were reported. Conclusion: The application of a topical combination of 2,4,6-octatrienoic acid and urea twice daily for 60 consecutive days is a safe and effective treatment for hyperkeratotic AK lesions. Funding: Giuliani SpA.

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... As far as the authors know, this is the only study that has used this agent to treat AKs. Patients in a phase IV study applied a topical cream containing 2,4,6-octatreinoic acid and urea twice daily for 2 months [80]. At the 3-month follow-up visit, 82.5% of patients achieved complete elimination of their AK lesions [80]. ...
... Patients in a phase IV study applied a topical cream containing 2,4,6-octatreinoic acid and urea twice daily for 2 months [80]. At the 3-month follow-up visit, 82.5% of patients achieved complete elimination of their AK lesions [80]. No side effects were reported although images provided in the article show common side effects such as erythema and crusting [80]. ...
... At the 3-month follow-up visit, 82.5% of patients achieved complete elimination of their AK lesions [80]. No side effects were reported although images provided in the article show common side effects such as erythema and crusting [80]. Patients were followed clinically and therefore lack histologic confirmation of lesion treatment. ...
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Purpose of Review Field cancerization describes the phenomenon that multiple heterogenous mutations may arise in an area exposed to chronic carcinogenic stimuli. Advances in the understanding of cutaneous field cancerization have led to novel therapeutic approaches to the management of actinic keratoses (AKs). Herein, we review the literature on the pathophysiology and emerging research of field cancerization in dermatology. Recent Findings The classification systems for grading AK lesions are being refined with investigations focusing on their clinical utility. There is a growing shift toward field-directed treatment for AKs as the importance of field cancerization becomes clearer. Current field-directed therapies are being optimized and novel therapeutic modalities are being studied. Summary Field cancerization underlies the transformation of photodamaged skin into AKs and potentially cutaneous squamous cell carcinoma (cSCC). Clinically meaningful classification systems for AKs are needed to better inform decisions regarding treatment. As we learn more about the role of field characterization in photodamage, AKs, and cSCCs, therapeutic strategies are becoming more field-directed rather than lesion-directed.
... A more intense approach is suggested in immunosuppressed subjects and when AK lesions are present in particular body areas (nose, eyelids, ears, lips) [24]. Therefore, low-dose 0.5% 5-fluorouracil/SA [25] and topical imiquimod (5% cream) [26] have been reported as effective and well-tolerated Previous studies reported the efficacy of a product containing 2,4,6-octatrienoic acid for both the prevention and treatment of non-hyperkeratotic [27] and hyperkeratotic AKs [28]. ...
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IntroductionActinic keratosis (AK) consists of skin lesions with a milder degree of keratinocytic atypia. It can be also referred to as “field of cancerization,” which can potentially evolve to cutaneous squamous cell carcinoma (SCC). Several therapeutic options are currently available, but not all are indicated on hyperkeratotic lesions. This study aimed to test the efficacy and tolerability of a medical device containing 2,4,6-octatrienoic acid and urea for the treatment of hyperkeratotic AK lesions.Methods Seventy male and female subjects with grade III AK were enrolled in this randomized double-blind parallel-group study. The product was applied once daily for three consecutive months. The primary efficacy endpoint was the reduction in the mean number of AK lesions per subject from baseline (T0) to the end of the trial (T1) and 3 months after the end of the treatment period (T2). Therefore, clearance of target AK lesions at the end of the treatment period and local skin reaction score (LSR) versus baseline were evaluated.ResultsThere was a decrease of mean values from baseline to visit T2 in both treatment groups, but the decrease (versus baseline values) was more evident in the Kerà K2 group than in the placebo group (−42.78, SD 26.53, versus −6.20, SD 31.57), and the difference was statistically significant (p < 0.001). For 70 subjects (56.7%) in the Kerà K2 group and 3 (11.54%) in the placebo group, a significant (p < 0.005) partial clearance was evidenced. The product was well tolerated, and no serious adverse events were reported during the duration of the trial. Subject self-assessment of acceptability, local tolerability, and the cosmetic result was good at both T1 and T2 for both groups.Conclusions The medical device has demonstrated good efficacy in the reduction of visible AKs, encouraging its use.
... The 2,4,6-octatrienoic acid has valuable pharmaceutical applications, acting as a promoter of melanogenesis with antioxidant defense in normal human melanocytes, 30 and is used in the treatment of hyperkeratotic actinic keratosis. 31 We have attempted to improve the 2,4,6octatrienoic acid titer by increasing the malonyl-CoA pool in the cells by employing the fatty acid synthase inhibitor cerulenin ( Figure S14, Supporting Information). This did not have a significant effect on the titer of the acid product per liter of cell culture, although given the negative affect of cerulenin on E. coli growth rate, this does suggest more 2,4,6-octatrienoic acid is made per biomass. ...
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Conjugated alkenes such as dienes and polyenes have a range of applications as pharmaceutical agents and valuable building blocks in the polymer industry. Development of a renewable route to these compounds provides an alternative to fossil fuel derived production. The enzyme family of the UbiD decarboxylases offers substantial scope for alkene production, readily converting poly unsaturated acids. However, biochemical pathways producing the required substrates are poorly characterized, and UbiD-application has hitherto been limited to biological styrene production. Herein, we present a proof-of-principle study for microbial production of polyenes using a bioinspired strategy employing a polyketide synthase (PKS) in combination with a UbiD-enzyme. Deconstructing a bacterial iterative type II PKS enabled repurposing the broad-spectrum antibiotic andrimid biosynthesis pathway to access the metabolic intermediate 2,4,6-octatrienoic acid, a valuable chemical for material and pharmaceutical industry. Combination with the fungal ferulic acid decarboxylase (Fdc1) led to a biocatalytic cascade-type reaction for the production of hepta-1,3,5-triene in vivo. Our approach provides a novel route to generate unsaturated hydrocarbons and related chemicals and provides a blue-print for future development and application.
... Finally, a phase IV clinical study showed that topical application of a PPARγ modulator (2,4,6-octatrienoic acid) in combination with urea was a safe and effective treatment for hyperkeratotic actinic keratosis. 39 However, while 2,4,6-octatrienoic acid requires PPARγ for its activity, it is not clear from this study whether this agent acted as a direct PPARγ ligand. ...
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Actinic keratoses (AK) are considered a worldwide problem with continuously increasing incidence. They clinically presents as rough or scaly plaques and are histologically characterized by a proliferation of atypical keratinocytes limited to the epidermis. AK is considered as an early step in the continuum of transformation from normal skin to invasive squamous cell carcinoma (SCC). These lesions develop on a background of field cancerization in which chronically UV- damaged-areas have accumulated molecular changes, but remain clinically normal for prolonged periods. The presence of certain clinical features of AK, such as large size, ulceration, or bleeding, suggests an increased risk of disease progression. The risk is also increased by evidence of extensive solar damage, advanced age, and immune-suppression. Many treatment modalities are available, although recent developments have focused on the management of the whole actinically damaged field. In this regard, several topical drugs have been approved, differing in efficacy, side effects, application and cost. Research is continuing aiming in the development of the "ideal" treatment which combines high clearance rates with few side effects, short treatment duration and low costs. Herein, we aim to give an overview on current treatment modalities including their mechanism of action, application scheme and common side effects. Furthermore, recent patents in the field and future aspects are discussed in this review.
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To evaluate the efficacy and safety of 5% imiquimod cream compared with vehicle in the treatment of actinic keratosis (AK). Two phase 3 randomized, double-blind, parallel-group, vehicle-controlled studies. Twenty-six ambulatory care offices, including dermatologists in private practice or research centers. Four hundred ninety-two patients, 18 years and older, with 4 to 8 AK lesions in a 25-cm(2) treatment area on the face or the balding scalp were randomized; an additional 162 patients underwent screening but were ineligible. Patients applied 5% imiquimod (Aldara) or vehicle cream to the treatment area once daily, 3 times per week, for 16 weeks, followed by an 8-week posttreatment period. Complete clearance rate (proportion of patients at the 8-week posttreatment visit with no clinically visible AK lesions in the treatment area), partial clearance rate (proportion of patients at the 8-week posttreatment visit with a >/=75% reduction in the number of baseline AK lesions in the treatment area), and frequency and severity of adverse events and local skin reactions were measured. Complete and partial clearance rates for imiquimod-treated patients (48.3% and 64.0%, respectively) were clinically and statistically significantly higher than for vehicle-treated patients (7.2% and 13.6%, respectively). The median percentage reduction of baseline lesions was 86.6% for the imiquimod-treated group and 14.3% for the vehicle-treated group. The 5% imiquimod cream dosed 3 times weekly for 16 weeks is safe and effective for the treatment of AK.
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Background: Actinic keratosis (AKs) are premalignant skin lesions characterized by high rate of transformation in squamous cell carcinoma if not treated. Pre-clinical published data on parrodiene-derivative 2,4,6-octatrienoic acid, encourages us to study andto evaluate the effect of a topical product containing it in patients affected by mild to moderate actinic keratosis. Methods: 70 subjects with at least 1-3 clinically diagnosed actinic keratosis lesions, nonhyperkeratotic, non-hypertrophic, localized on the face (I-II degree actinic keratosis) were enrolled in the study. The product was applied twice/day for 60 consecutive days. Results: After 60 days of treatment, a significant improvement in lesions occurred as shown by the decrease in the AKESA score (p <0.05). Moreover, octatrienoic acid containing cream induced complete remission in 14 patients out of 70 (20%), (p <0.05) and a complete clinical response in 63/70 patients (90%; p <0.5; 95% confidence interval). Compared to baseline, a significant number of patients reported improvement of each AKESA subscoreafter 60 days of treatment: skin thickess improved in 46 patients (p <0.0001), erythema in 21 patients (p <0.0001) and atrophy in 57 patients (p <0.0348).The average pigmentation score significantly decreased from 1.50 to 0.79 (p <0.05). Conclusions: The results of the study, confirmed also by self-assessment, allow us not only to state that the use of topical octatrienoic acid was effective and well tolerated for topical treatment of AKs leading to overall clinical improvement in approximately 90% of subjects treated for 60 days.
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Actinic keratoses (AK) arise on sun-exposed regions of the skin. If left untreated, AK may progress to invasive squamous cell carcinoma (SCC), although the rate of progression is low. A practical treatment algorithm for the treatment of AK in standard situations has been published by the AKTeam™ expert panel. However, management of particular situations of AK with increasing/higher carcinoma risk or AK progressing into carcinomas with increased aggressiveness due to their anatomical location (risky areas), or in patients with an increased risk of SCC requires further discussion. These include AK on the dorsal hands, forearms, legs, periorbital region, eyelids, ears, or lips, and organ transplant recipients, patients undergoing treatment with carcinogenic agents, and patients with chronic lymphocytic leukemia.
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The chronic skin condition actinic keratosis (AK) is characterized by the formation of keratotic lesions of variable thickness that are poorly delimited. AK occurs on areas of the skin that have had long-term exposure to the sun or UV radiation. Although AKs may regress, they usually persist and can progress to squamous cell carcinoma (SCC). Clinicians are unable to predict which AKs will progress; therefore, both clinically visible lesions and subclinical, non-visible (i.e. the entire area affected by AK/field cancerization) should be treated. AK treatment options include lesion-directed therapies that target specific AK lesions and field-directed therapies that target multiple clinical lesions and the underlying field damage. This article reviews currently available treatment options in AK, with a focus on patient-applied field therapies, and their suitability according to specific disease characteristics and patient needs. Choice of treatment in AK depends on lesion-, patient- and treatment-related factors and should be individualized. Considerations when choosing a therapy include site of application, treatment duration, surface area of application, tolerability profiles and implications on adherence. Field-directed therapies treat clinical and subclinical damage (i.e. the entire area affected by AK), achieve high rates of sustained clearance of AKs and may reduce the risk of progression to SCC. There is a clear need for field therapies with short duration of treatment and predictable, short-lived, mild local skin reactions that can be used over a large surface area. Therapies with shorter and simpler treatment courses are often associated with better adherence than treatments with longer courses. These may, therefore, represent more appropriate choices in patients for whom convenience and/or adherence are an issue.
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Background: There are several clinical and histological classification systems for grading actinic keratosis (AK) lesions. The Olsen clinical classification scheme grades AK lesions according to their thickness and degree of hyperkeratosis (grades 1-3). The Roewert-Huber histological classification system grades AK lesions based on the extent of epidermal atypical keratinocytes (AK I-III). Objective: The aim of this study was to determine whether there is a correlation between these clinical and histological AK classification schemes. Methods: One AK lesion from patients in three pivotal clinical studies and routine practice was assessed clinically and histologically. A match in grading was defined as Olsen grade 1 being classified histologically as AK I, Olsen grade 2 as AK II and Olsen grade 3 as AK III. Results: Of the 892 lesions included, 29.0% were classified as Olsen grade 1, 59.6% as Olsen grade 2 and 11.3% as Olsen grade 3; 19.2% were histologically classified as AK I, 69.6% as AK II and 11.2% as AK III. Only 480 lesions (53.8%) had a matching clinical and histological classification. Of these matches, most were 'Olsen grade 2 = AK II' (83.1%). The Spearman's rank correlation coefficient for clinical and histological classification was r = 0.0499 (P = 0.137). Conclusions: Clinical classification of AK lesions using the system of Olsen does not accurately match histological classification of the same lesions using the system of Roewert-Huber. Consequently, it is not possible to draw conclusions about the histology of AK lesions from their clinical appearance. This finding reinforces the need to treat all AK lesions as well as field cancerization.
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Background Actinic keratoses (AK) are common photo-induced cutaneous lesions that may progress to invasive squamous-cell carcinoma and serve as a risk marker for skin cancer. Although numerous studies present the various therapeutic options for AK, publications that can be used to pragmatically guide dermatologists in their daily practice are limited. National and international guidelines have been published, however, they are based on clinical trials with highly selected patient populations and do not always capture the range of patients seen in everyday practice. Objective The objective of this expert panel of French dermatologists was to present an analysis of AK geared towards everyday practice, to express an informed opinion about most recent treatments, and to propose a treatment algorithm for AK for daily practice in France. Methods Over a 12 month period, six expert dermatologists in the field of AK (AKTeamTM expert panel) met regularly to formulate an opinion about treatment in everyday practice compared with the analysis of the literature and guidelines published since 1990. ResultsDefinitions, terminology, diagnosis and risk factors were summarized. Data from the literature and current practices related to the initial evaluation, indications for biopsy, therapeutic indications, therapeutic options and effectiveness, monitoring and prevention were discussed. A pragmatic treatment algorithm was formalized according to current data available. This practical algorithm distinguishes between different clinical situations depending on the number of AK, their hyperkeratotic or suspicious nature, and includes cryotherapy, curettage-electrocoagulation, 5% 5-fluorouracil, 3% diclofenac sodium, 5% imiquimod, 150 and 500 μg/g ingenol mebutate, lasers, photodynamic therapy and surgery. Conclusion This up-to-date expert opinions about AK and its treatment provide a management strategy and practical treatment algorithm for AK for French dermatologists to use.
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CONTEXT: Knowledge about the development of untreated actinic keratosis (AK) and their risk of progression into squamous cell carcinoma (SCC) is important. OBJECTIVES: Synthesis of primary data on the natural history of AK. METHODS: Systematic literature search (Medline, Medline in Process, Embase, Cochrane) on studies (cohort studies/control arms from RCTs) on the natural course of AK (a) progression and regression rates per lesion-year, (b) changes in the total lesion counts over time, (c) spontaneous field regression and recurrence rates; taking into account: studies on participants without immunosuppression and history of skin cancer, immunosuppressed patients, participants with history of skin cancer and sunscreen use. RESULTS: We indentified 24 eligible studies providing data on at least one of the outcomes. Progression rates of AKs to SCC ranged from 0% to 0.075%/lesion/year, with a risk of up to 0.53% per lesion when looking at participants with prior history of NMSC. Rates of regression of single lesions ranged between 15%-63% after one year. The data available on recurrence rates of single lesions one year after regression indicate a recurrence rate of between 15% and 53%. Data on the relative change of the total AK count over time are heterogeneous, with a range from -53% to +99.1%. Spontaneous complete field regression rates range from 0% to 21%, with recurrences in 57%. CONCLUSIONS: In general, the available data are limited. Important methodological limitations apply. Currently, no reliable estimates concerning the frequency of AKs developing into invasive carcinoma can be given, further studies are needed. This article is protected by copyright. All rights reserved.
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Topical photodynamic therapy (PDT) is a widely used non-invasive treatment for certain non-melanoma skin cancers, permitting treatment of large and multiple lesions with excellent cosmesis. High efficacy is demonstrated for PDT using standardized protocols in non-hyperkeratotic actinic keratoses, Bowen's disease, superficial basal cell carcinomas (BCC) and in certain thin nodular BCC, with superiority of cosmetic outcome over conventional therapies. Recurrence rates following PDT are typically equivalent to existing therapies, although higher than surgery for nodular BCC. PDT is not recommended for invasive squamous cell carcinoma. Treatment is generally well tolerated, but tingling discomfort or pain is common during PDT. New studies identify patients most likely to experience discomfort and permit earlier adoption of pain-minimization strategies. Reduced discomfort has been observed with novel protocols including shorter photosensitizer application times and in daylight PDT for actinic keratoses.
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Spreading pigmented actinic keratosis (SPAK) is a common, but uncommonly reported or appreciated, variant of classic actinic keratosis (AK). It can mimic different pigmented lesions, which may be benign (eg, solar lentigo) or malignant (eg, lentigo maligna). We sought to review current data and identify areas needing further research to establish diagnostic guidelines for SPAK and to increase awareness of this common entity. A literature search was performed in both PubMed and MEDLINE databases using the search terms "spreading pigmented actinic keratosis," "pigmented solar keratosis," "pigmented actinic," and "pigmented solar." Each article was retrieved, reviewed, and summarized. SPAK is a rarely reported lesion that can be difficult to distinguish from other benign and malignant pigmented lesions, including seborrheic keratosis, melanoma in situ (lentigo maligna type), and lentigo maligna melanoma. Located mainly on sun-exposed areas and with a size greater than 1.5 cm, the lesion typically spreads laterally. Pathologically, the lesion resembles classic AK with increased basal melanization. The malignancy potential has not yet been elucidated but destructive therapies such as cryotherapy are recommended. Reports not yet published or not included in the comprehensive databases we used may exist that were not analyzed. SPAK can be associated with adjacent melanoma in situ; therefore, its diagnosis merits increased suspicion for coexisting melanoma.
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This double-blind, vehicle-controlled, multicenter study evaluated the efficacy and safety of a new topical antineoplastic agent, masoprocol, in the treatment of actinic keratoses of the head and neck. Of the 113 patients who applied topical masoprocol twice a day for 14 to 28 days, there was a mean decrease in actinic keratoses from 15.0 to 5.4 and a median percent reduction from baseline actinic keratosis count of 71.4% at the 1-month follow-up visit. Comparable numbers for the vehicle-treated group were 13.4 to 11.1 actinic keratoses and 4.3% median percent reduction. Irritation, as manifested by erythema or flaking, occurred in 61.5% of topical masoprocol-treated patients versus 26.7% of those treated with vehicle and did not correlate with clinical response. Topical masoprocol appears to be useful in the treatment of actinic keratoses.
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One thousand and forty people aged 40 years and over, 616 (59.2%) of whom had solar keratoses, were followed for 12 months. Two hundred and twenty-four people (36.4%) had a spontaneous remission of at least one of their solar keratoses. A total of 485 lesions (25.9%) underwent spontaneous remission out of the 1873 lesions that were present at the first examination of these 224 people. There was no significant difference between the number of lesions present at the initial examination in those who had a spontaneous remission compared with those who did not. There was a 21.8% increase in the total number of solar keratoses in the 1040 people studied in the 12-month period, due to new lesions forming at the same time as remissions were occurring. The incidence rate of squamous cell carcinoma occurring in the people with solar keratoses was 0.24% for each solar keratosis present at the original examination. With a substantial proportion of solar keratoses remitting spontaneously, plus the low rate of malignant transformation and the low potential for metastasis to occur from squamous cell carcinoma arising in a solar keratosis, the rationale of treating all solar keratoses appears questionable.
Article
The presence of solar keratoses on the skin is one of the major risk factors for basal cell and squamous cell carcinomas, which constitute a growing public health problem in today's white populations. In spite of this, little is known of the natural history of solar keratoses. We conducted follow-up studies to monitor the incidence, regression, and recurrence rates of solar keratoses in a random sample (N = 96) of the Nambour community in Queensland. At baseline, 43 participants (46%) were diagnosed with at least one solar keratosis [26 men (55%), 17 women (37%)] with a total count of 494 prevalent solar keratoses. The distribution of lesions per person was highly skewed, with 11 individuals (12%) having 65% of the total number of solar keratoses. During 12 mo of follow-up, 614 incident solar keratoses were diagnosed (549 in men and 65 in women); 526 solar keratoses regressed and 53 prevalent solar keratoses recurred, giving a net 45% increase in solar keratosis numbers in men (from 354 to 512 solar keratoses) and a net 44% reduction in women (from 114 to 64). Regression rates were higher in prevalent (74%) than incident (29%) solar keratoses. Solar keratosis prevalence increased with age in both sexes, and individuals with solar keratoses at baseline were over seven times more likely to develop additional solar keratoses in the next 12 mo than those without prevalent solar keratoses at baseline. These results show that the natural history of solar keratoses in the community is one of high turnover and that a small percentage of susceptible individuals carry the major burden of solar keratoses in the community.
Article
Increasing evidence suggests imiquimod may be a safe therapeutic option for the treatment of actinic keratosis (AK). The diagnosis and assessment of most AK lesions is made clinically, without histologic confirmation. A phase III, randomized, double-blind, parallel group, vehicle-controlled study evaluated the efficacy of imiquimod 5% cream compared with vehicle in the treatment of AK lesions on the face and balding scalp including pretreatment and posttreatment biopsy specimens. A total of 286 patients at 18 centers in 6 European countries with histologically confirmed AK were randomized to either imiquimod 5% cream or vehicle cream. Study cream was applied once per day, 3 days per week, for 16 weeks. Clearance of AK lesions was clinically and histologically assessed at an 8-week posttreatment visit. The complete clearance rate for the imiquimod group was 57.1% versus 2.2% for the vehicle group (P <.001). The partial clearance rate (> or =75% reduction in baseline lesions) for the imiquimod group was 72.1% versus 4.3% for the vehicle group (P <.001). The most common side effects were erythema, scabbing/crusting, and erosions/ulceration. For the imiquimod group the incidence of severe erythema, scabbing/crusting, or erosions/ulceration was 30.6%, 29.9%, and 10.2%, respectively. Imiquimod 5% cream used 3 times per week for 16 weeks is an effective treatment for AK. Clinical clearance was established by both clinical observation and histologic analysis.
Article
Actinic keratosis is a UV light-induced lesion and develops mostly in fair-skinned patients being susceptible to solar damage. The term actinic keratosis (AK) describes clinically ill-defined reddish to reddish-brown scaly lesions on erythematous base in areas damaged severely by sunlight. The term does not imply anything about the biology or histopathology. Actinic keratoses (AKs) have been recognized as precursor of cancer or of precancerous lesions in the past but today they are considered as an early in situ squamous cell carcinoma 1,2 and are categorized in several classifications with subdivisions into three grades depending on the amount of atypical keratinocytes in the epidermis.3–6 The incidence of development of AK in caucasians increases with age, proximity to the equator and outdoor occupation. Australia has the highest skin cancer rate in the world. AKs are discovered in up to 40–50% of the Australian population older than 40 years.7 AKs are the most common malignant lesion of the skin.8–12