Aldara References

1: Gene Ther. 2005 Jun 2;

Imiquimod - Aldara and S-27609 as adjuvants of DNA vaccination in a transgenic murine model of HER2/neu-positive mammary carcinoma.

Smorlesi A, Papalini F, Orlando F, Donnini A, Re F, Provinciali M.

1Laboratory of Tumor Immunology, Immunology Center, INRCA Research Department, Ancona, Italy.

DNA vaccination against HER-2/neu is an effective way to induce an immune response able to oppose the spontaneous development of mammary tumours occurring in HER-2/neu transgenic mice. In this study, we have evaluated the potential of Imiquimod - Aldara and the analogue S-27609 as adjuvants of DNA vaccination against HER-2/neu in transgenic mice. The association of a DNA vaccine encoding a portion of rat HER2/neu with either Imiquimod - Aldara or S-27609 was found to delay the development of spontaneous mammary tumours and to reduce their incidence, in comparison with DNA vaccination alone. Almost 80 or 40% of tumour-free mice were found at the end of measurement time in mice vaccinated and supplemented with Imiquimod - Aldara or S-27609, respectively. The antitumour preventive effect was associated with increased antibody and cell-mediated immune responsiveness against HER-2/neu. In mice vaccinated and supplemented with Imiquimod - Aldara, a small but significant increase of rat p185(neu)-specific cytotoxicity and of IFN-gamma and IL-2-producing CD8T cells, together with a reduction of IL-4-producing CD4T cells, and a switch from an IgG1 towards a IgG2a phenotype of anti-p185(neu) antibodies, suggested a TH1 polarization of the immune response. The immunoregulatory efficacy of S-27609 was lower than that observed for Imiquimod - Aldara. These data highlight the potential of Imiquimod - Aldara, and, to a lower extent, of S-27609, as immunological adjuvants of therapeutic DNA vaccines.Gene Therapy advance online publication, 2 June 2005; doi:10.1038/sj.gt.3302559.

2: Am J Clin Dermatol. 2005;6(3):195-200.

Imiquimod - Aldara: in superficial Basal cell carcinoma.

Oldfield V, Keating GM, Perry CM.

Adis International Inc., Yardley, Pennsylvania, USA.

black triangle Imiquimod - Aldara, available as a 5% cream, is a new topical treatment for adults with superficial basal cell carcinoma (BCC). The exact mechanism of action of Imiquimod - Aldara in superficial BCC is unknown. Imiquimod - Aldara may act as a toll-like receptor-7 agonist, and is thought to exert its anti-tumor effect via modification of the immune response and stimulation of apoptosis in BCC cells.black triangle Topical Imiquimod - Aldara 5% cream effectively increased clinical and histologic clearance of single superficial BCC lesions compared with vehicle in patients enrolled in two large, well designed trials. Patients applied Imiquimod - Aldara five or seven times per week or vehicle for 6 weeks, and the composite clearance rates at 12 weeks post-treatment for the corresponding treatment groups were 75%, 73%, and 2%, respectively.black triangle In a trial investigating the long-term efficacy of Imiquimod - Aldara 5% cream following application five times per week for 6 weeks, a clinical clearance rate of 90% was reported at the initial 12-week post-treatment examination. The estimated rate of clinical clearance at the 1-year follow-up visit was 84%.black triangle Application site and local skin reactions were the most common adverse events reported by Imiquimod - Aldara recipients. The severity of erythema, erosion, and scabbing/crusting correlated positively with the composite and histologic response rates.

3: Rev Med Liege. 2005 Apr;60(4):207-9.

How I treat ... basal cell carcinoma by Imiquimod - Aldara

Pierard-Franchimont C, Nikkels AF, Paquet P, Quatresooz P, Pierard GE.

CHU du Sart Tilman, Service de Dermatopathologie, Liege.

Basal cell carcinoma is the most frequent cancer in humans. Several clinical types are distinguished. They are bound to distinct evolutive prognosis. The surgical excision is the treatment of choice which is rarely followed by recurrence. However, when the lesion is superficial and non aggressive and when the body site is adequate, topical applications of Imiquimod - Aldara can provoke the neoplastic regression. This type of immunotherapy brings 70 to 90% complete remission. A medical follow-up of the treated site is mandatory for a couple of years.

4: Pediatr Dermatol. 2005 May-Jun;22(3):254-6.

Proliferating hemangioma of infancy: successful treatment with topical 5% Imiquimod - Aldara cream.

Hazen PG, Carney JF, Engstrom CW, Turgeon KL, Reep MD, Tanphaichitr A.

Department of Dermatology, Case-Western Reserve University School of Medicine, Cleveland, Ohio, USA.

A 4-month-old girl had a proliferating hemangioma of infancy (infantile hemangioma) affecting the chest wall. The lesion had appeared 1 week after birth, demonstrating both superficial and deep components, and was rapidly enlarging. It had become painful and superficially eroded. Treatment with topical 5% Imiquimod - Aldara cream three times a week was associated with signs of involution after 10 days, and complete resolution after 10 weeks of therapy. The treatment was well tolerated.

5: Br J Dermatol. 2005 May;152(5):939-47.

Imiquimod - Aldara 5% cream for the treatment of superficial basal cell carcinoma: results from a randomized vehicle-controlled phase III study in Europe.

Schulze HJ, Cribier B, Requena L, Reifenberger J, Ferrandiz C, Garcia Diez A, Tebbs V, McRae S.

Clinique Dermatologique, Strasbourg, France.

BACKGROUND: Imiquimod - Aldara is an immune response modifier that acts through toll-like receptor 7 to induce cytokine production and a subsequent innate and adaptive cell-mediated immune response. Clinical studies have demonstrated clinical and histological clearance of superficial basal cell carcinoma (sBCC) after treatment with Imiquimod - Aldara 5% cream. OBJECTIVES: To evaluate the safety and clinical efficacy of Imiquimod - Aldara (Aldaratrade mark; 3M Pharmaceuticals, St Paul, MN, U.S.A.) 5% cream for the treatment of sBCC in a multicentre, randomized, parallel, vehicle-controlled, double-blind, phase III clinical study conducted at 26 centres in Europe. METHODS: Subjects who had at least one histologically confirmed sBCC tumour were randomized to apply Imiquimod - Aldara or vehicle cream to the target tumour once daily, seven times per week (7 x/week) for 6 weeks. The target tumour location was identified with an indelible ink mark before treatment initiation. The treated tumour site was clinically assessed for treatment response at 12 weeks post-treatment and was then excised for histological evaluation. Efficacy assessments included the composite response rates (proportion of subjects with clinical and histological clearance) and response rates solely based on histology (proportion of subjects with histological clearance). Safety assessments, which included adverse events and scoring of local skin reactions (LSRs), were carried out throughout the study. RESULTS: In total, 166 subjects were enrolled in this study. For the intent-to-treat dataset, there was a statistically significant difference between Imiquimod - Aldara and vehicle groups for both composite clearance rates (clinical and histological assessments) and histological clearance rates. Composite clearance was demonstrated in 77% and 6% of subjects treated with Imiquimod - Aldara and vehicle cream, respectively. Histological clearance was demonstrated in 80% and 6% of subjects treated with Imiquimod - Aldara and vehicle cream, respectively. The most frequently reported safety findings were investigator-assessed LSRs and spontaneous reports by subjects of application site reactions, which occurred more frequently in the Imiquimod - Aldara group than in the vehicle group. CONCLUSIONS: Imiquimod - Aldara 5% cream administered 7 x/week for 6 weeks is a safe and effective treatment for sBCC when compared with vehicle cream.

6: J Med Chem. 2005 May 19;48(10):3481-91.

Synthesis and structure-activity-relationships of 1H-imidazo[4,5-c]quinolines that induce interferon production.

Gerster JF, Lindstrom KJ, Miller RL, Tomai MA, Birmachu W, Bomersine SN, Gibson SJ, Imbertson LM, Jacobson JR, Knafla RT, Maye PV, Nikolaides N, Oneyemi FY, Parkhurst GJ, Pecore SE, Reiter MJ, Scribner LS, Testerman TL, Thompson NJ, Wagner TL, Weeks CE, Andre JD, Lagain D, Bastard Y, Lupu M.

3M Pharmaceuticals, 3M Center, Building 270-4S-02, St. Paul, Minnesota 55144-1000, USA.

1H-Imidazo-[4,5-c]quinolines were prepared while investigating novel nucleoside analogues as potential antiviral agents. While these compounds showed no direct antiviral activity when tested in a number of cell culture systems, some demonstrated potent inhibition of virus lesion development in an intravaginal guinea pig herpes simplex virus-2 assay. We have determined that the in vivo antiviral activity can be attributed to the ability of these molecules to induce the production of cytokines, especially interferon (IFN), in this model. Subsequently, we found that the compounds also induce in vitro production of IFN in human peripheral blood mononuclear cells (hPBMCs). The in vitro results reported herein and the in vivo results reported previously led to the discovery of Imiquimod - Aldara, 26, which was developed as a topical agent and has been approved for the treatment of genital warts, actinic keratosis, and superficial basal cell carcinoma.

7: Int J Dermatol. 2005 May;44(5):428-34.

Successful treatment of malignant melanoma in situ with topical 5% Imiquimod - Aldara cream.

Ray CM, Kluk M, Grin CM, Grant-Kels JM.

University of Connecticut Health Center, Department of Hematology/Oncology, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USA.

BACKGROUND: Current treatment recommendations for malignant melanoma in situ include surgical excision with at least 0.5 cm margins. On the head or neck, obtaining adequate surgical margins for melanoma can be challenging and often disfiguring. In addition, some elderly patients may not be good surgical candidates and may request less aggressive interventions. METHODS: We report herein three cases of malignant melanoma in situ on the face treated with topical Imiquimod - Aldara cream. RESULTS: Complete regression of malignant melanoma in situ was observed on treatment with 5% topical Imiquimod - Aldara cream. The varied treatment regimens, rationale for using Imiquimod - Aldara rather than performing surgery, and the possible mechanisms of action are discussed. CONCLUSIONS: Topical Imiquimod - Aldara can be used successfully for the treatment of malignant melanoma in situ on the face.

8: J Cutan Med Surg. 2005 May 5;

Epidermodysplasia Verruciformis in Two Half brothers with HIV Infection.

Hu W, Nuovo G, Willen M, Somach S.

Department of Dermatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA .

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare disorder characterized by widespread flat and common verrucae. From 25% to 50% of EV cases are inherited, usually with an autosomal recessive pattern. An X-linked inheritance has also been reported. Many EV patients have a cellular immunity defect. HIV-associated lesions have been found to contain HPV-5, HPV-8, and HPV-20. OBJECTIVE: We describe two HIV-positive Hispanic maternal half brothers who presented with asymptomatic polyangular papules and plaques on the face, trunk, and extremities and which first appeared 4-5 years prior. The histopathology is consistent with EV. HPV-8 was detected by in situ hybridization. The patients were treated with topical Imiquimod - Aldara for two months without improvement. CONCLUSION: To our knowledge, this is the first reported case of epidermodysplasia verruciformis in HIV-positive pediatric patients.

9: J Cutan Med Surg. 2005 May 5;

Viral and Nonviral Uses of Imiquimod - Aldara: A Review.

Gupta AK, Cherman AM, Tyring SK.

Division of Dermatology, Department of Medicine, Sunnybrook and Women's College Health Science Center (Sunnybrook site) and the University of Toronto, Toronto, Ontario, Canada.

BACKGROUND: Imiquimod - Aldara is a topical immunomodulator that is indicated for the treatment of external genital and perianal warts. This drug has been recently approved for the treatment of actinic keratoses and superficial basal cell carcinoma. There is a growing body of evidence for its effectiveness in treating a variety of other skin conditions. OBJECTIVE: This review examines the role of Imiquimod - Aldara 5% cream in the treatment of skin diseases such as actinic keratoses, basal cell carcinoma, Bowen's disease, lentigo maligna, and extramammary Paget's disease. METHODS: Published literature containing the words "Imiquimod - Aldara" or "Aldara" was reviewed and summarized. RESULTS: This agent has demonstrated indirect antiviral and antitumor effects in animal models. Although the exact mechanism of action is unknown, Imiquimod - Aldara is an agonist for toll-like receptor (TLR) 7 and is thought to act by inducing cytokines, such as interferon alpha (IFN-alpha), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-alpha). These cytokines trigger the immune system to recognize the presence of a viral infection or tumor and the associated lesion is ultimately eradicated. Side effects are generally well tolerated with local skin reactions reported most frequently. CONCLUSION: Imiquimod - Aldara has been shown to be a safe and effective treatment for a variety of skin conditions.

10: Int J Tissue React. 2005;27(1):31-8.

Imiquimod - Aldara 5% cream: a new treatment for bowen's disease.

Mandekou-Lefaki I, Delli F, Koussidou-Eremondi T, Mourellou-Tsatsou O, Dionyssopoulos A.

State Hospital for Skin and Venereal Diseases, Thessaloniki, Greece.

Bowen's disease (BD) is a squamous cell carcinoma in situ. Recent studies suggest that human papilloma virus plays an important role in the development of BD. We investigated whether Imiquimod - Aldara 5%, a topical immune response modifier, is an effective treatment for BD in five immunocompetent patients. The lesions were one genital and four extragenital. The frequency of application varied from three times weekly up to twice daily, and treatment duration ranged from 8-24 weeks. Four patients achieved clinical and histological cure. The patient with the genital lesion gained an important reduction in size and infiltration, which enabled surgical removal of the remaining lesion with good functional and cosmetic result. Our results suggest that topical Imiquimod - Aldara 5% is an effective treatment for BD through its viral and antitumor effects.