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Korman N, Moy R, Ling M, Matheson R, Smith S, McKane S et al.. Dosing with 5% imiquimod cream 3 times per week for the treatment of actinic keratosis: results of two phase 3, randomized, double-blind, parallel-group, vehicle-controlled trials. Arch Dermatol 141: 467-473

Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, Ohio, USA.
Archives of Dermatology (Impact Factor: 4.31). 04/2005; 141(4):467-73. DOI: 10.1001/archderm.141.4.467
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ABSTRACT 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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Available from: Mark Russell Ling, Aug 07, 2014
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    • "Imiquimod (5%) cream is an immune response modi�er that acts via stimulation of a Toll-like receptor culminating in malignant cell apoptosis and a local 1-based immune response. Randomised controlled trials have demonstrated its efficacy both clinically and histologically over a 16-week treatment course [33] [34]. Complete clinical clearance was achieved in 47% of patients and partial in 64%. "
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    ABSTRACT: Solid organ transplant recipients are predisposed to actinic keratoses (AK) and nonmelanoma skin cancers, owing to the lifelong immunosuppression required. Today, increasing numbers of organ transplants are being performed and organ transplant recipients (OTRs) are surviving much longer. Photodynamic therapy (PDT) is proving a highly effective treatment modality for AK amongst this susceptible group of patients. Following an overview of the pathogenesis of AK amongst OTRs, the authors review current safety and efficacy data and how this relates to the role of PDT for the treatment of AK in OTRs.
    01/2013; 2013:349526. DOI:10.1155/2013/349526
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    • "In addition, several controlled clinical trials as well as many smaller series of cases and case reports have demonstrated that imiquimod is also effective against a variety of primary skin cancers as well as cutaneous metastases of some malignancies. Cutaneous tumors that have responded well to topical treatment with imiquimod include basal cell carcinomas (Sterry et al., 2002; Bath- Hextall et al., 2004; Geisse et al., 2004; Gollnick et al., 2005; Schulze et al., 2005), keratoacanthomas (Dendorfer et al., 2003; Peris et al., 2003), actinic keratoses (Stockfleth et al., 2001, 2002; Lebwohl et al., 2004; Szeimies et al., 2004; Korman et al., 2005) and Bowen's disease (the latter two entities represent epidermal carcinoma in situ) (Patel et al., 2006; Peris et al., 2006), cutaneous metastases of melanoma (Steinmann et al., 2000; Bong et al., 2002; Ugurel et al., 2002; Wolf et al., 2003; Zeitouni et al., 2005), some cases of primary melanoma in situ (Fleming et al., 2004; Kamin et al., 2005; Ray et al., 2005; Wolf et al., 2005; Lonsdale-Eccles et al., 2006) and cutaneous T-cell lymphomas (Suchin et al., 2002; Dummer et al., 2003b; Chong et al., 2004; Deeths et al., 2005). Clinical responses of cutaneous neoplasias to topical treatment with imiquimod have also been observed in difficult-to-treat patient populations, such as organ transplant patients under immunosuppressive therapy (Smith et al., 2001; Prinz et al., 2004; Brown et al., 2005) or Xeroderma pigmentosum patients suffering from rapid development of multiple UV-induced cutaneous malignancies (Giannotti et al., 2003; Roseeuw, 2003). "
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    ABSTRACT: Small-molecule agonists at Toll-like receptor 7 (TLR7) and TLR8 have sparked a vivid interest in cancer research owing to their profound antitumoral activity. The lead compound of the imidazoquinoline family, imiquimod, is marketed as a topical formulation. It is efficacious against many primary skin tumors and cutaneous metastases. Using different imidazoquinoline species, distinct functions of TLR7 and TLR8 have been discovered. The predominant antitumoral mode of action of these agents is TLR7/8-mediated activation of the central transcription factor nuclear factor-kappaB, which leads to induction of proinflammatory cytokines and other mediators. Cutaneous dendritic cells are the primary responsive cell type and initiate a strong Th1-weighted antitumoral cellular immune response. Recent research has shown that dendritic cells themselves acquire direct antitumoral activity upon stimulation by imiquimod. In addition, there are a number of secondary effects on the molecular and cellular level that can be explained through the activation of TLR7/8. The proinflammatory activity of imiquimod, but not resiquimod, appears to be augmented by suppression of a regulatory mechanism, which normally limits inflammatory responses. This is achieved independently of TLR7/8 through interference with adenosine receptor signaling pathways. Finally, at higher concentrations imiquimod exerts Bcl-2- and caspase-dependent proapoptotic activity against tumor cells.
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    • "Better clearance was seen in subjects with the most severe adverse events (Stockfleth et al., 2004). Chen et al. (2003), found that better clearance occurred in subjects with larger increases in AK lesions during initial therapy, and Korman et al. (2005), found that both an increase in the number of lesions and intensity of local skin reaction was associated with better clearance rates. "
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    ABSTRACT: Benefit and harm associated with treating actinic keratosis (AK) with the immune response modifier imiquimod was assessed using published randomized-controlled trials. Five randomized double-blind trials lasted 12-16 weeks and treated 1,293 patients. Complete clearance occurred in 50% of patients treated with imiquimod, compared to 5% treated with vehicle, and the number needed to treat (NNT) for one patient to have their keratosis completely cleared after 12-16 weeks was 2.2 (95% confidence interval 2.0-2.5). For partial (>/=75%) clearance the NNT was 1.8 (1.7-2.0). The proportion of patients with any adverse event, any local adverse event, or any treatment-related adverse event was substantially higher with imiquimod than with vehicle, and numbers needed to harm for one additional adverse event with imiquimod over 12-16 weeks ranged from 3.2 to 5.9. Particular local adverse events with imiquimod included erythema (27%), scabbing or crusting (21%), flaking (9%), erosion (6%), edema (4%), and weeping (3%). Imiquimod 5% cream was effective in the treatment of AK, preventing potential development of squamous cell carcinoma. Future investigation might be aimed at elucidating optimal dosing to minimize adverse events without detriment to efficacy, and evaluating long-term recurrence.
    Journal of Investigative Dermatology 06/2006; 126(6):1251-5. DOI:10.1038/sj.jid.5700264 · 6.37 Impact Factor
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