Aldara
Successful treatment of actinic keratosis with imiquimod cream 5%: a report of six cases.

Stockfleth E, Meyer T, Benninghoff B, Christophers E.

Department of Dermatology, University of Kiel, Schittenhelmstrasse 7, D-24105 Kiel, Germany. E.Stockfleth web.de

BACKGROUND: Actinic keratoses (AK) are premalignant lesions, which are routinely treated by destructive procedures such as cryotherapy, electrodessication or topical 5-fluorouracil. OBJECTIVES: The aim of this study is to report six cases of AK treated with a potential new topical therapy, imiquimod. METHODS: Subjects included in this study had suffered with recurrent AK for between 5 and 16 years. All six men were treated with imiquimod 5% cream three times a week for 6-8 weeks. In the event of a local skin reaction treatment was modified to two times per week. RESULTS: All the AK lesions were successfully cleared after treatment with imiquimod cream 5% for 6-8 weeks. Histologically, no apparent signs of persisting AK could be detected, and no recurrences were reported during follow up. CONCLUSIONS: This study suggests that imiquimod may be useful as a new therapy for the treatment of actinic keratoses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11359396&dopt=Abstract imiquimod Aldara



Aldara
Introduction

Maw R, Aractingi S.

Department of Genitourinary Medicine, The Royal Victoria Hospital, Level 3b, Grosvenor Road, Belfast BT12 6BA, Ireland.

Anogenital warts have become one of the most common sexually transmitted diseases reported in the Western World. The frustration of treatment for both patient and carer is well recognised. Current available methods rely principally on ablation of visible lesions, with hospital-based treatments often requiring multiple attendance by out-patients. Overall, the current failure rate, recurrence rate, and side-effects of these treatments are highly unsatisfactory. Imiquimod, recently launched in the US under the brand name Aldaratrade mark cream, represents the most interesting and innovative approach to therapy to become available in many years. Imiquimod is an immune response modifier, therefore this symposium report addresses the vital issues of the immune based response to human papilloma virus (HPV) infection, as well as the problems of persistence caused by HPV disease. The mechanisms by which imiquimod can induce an inflammatory and cell-mediated response are discussed. Also reviewed are the consequent imiquimod clinical results and the reasons why they show great cause for optimism in HPV treatment. As a home-based effective treatment with a low recurrence rate, imiquimod has already generated enthusiasm on an international scale. This symposium report presents the thoughts and experiences of medical specialists from various countries regarding the treatment of genital HPV infections and the place for imiquimod in clinical practice.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=0010388514&dopt=Abstract imiquimod Aldara



Aldara
Squamous cell carcinoma in situ (Bowen's disease) in renal transplant patients treated with 5% imiquimod and 5% 5-fluorouracil therapy.

Smith KJ, Germain M, Skelton H.

Departments of Dermatology and Pathology, University of Alabama, 1720 University Blvd., Birmingham, AL 35294-0009, USA.

BACKGROUND: Depending upon the patient's age at transplant, skin type, sun exposure, and the need for immunosuppressive therapy to prevent rejection, there is escalation in the development of cutaneous malignancies in organ transplant patients a number of years after transplantation. Thus, with the expansion in these procedures over the past decades, and the ever-lengthening survival of these patients, we are seeing an increase in cutaneous malignancies in this patient population. OBJECTIVE: To determine if combined therapy with 5% 5-fluorouracil and 5% imiquimod may be useful in the treatment of squamous cell carcinoma in situ. METHODS: We present five renal transplant patients, all more than 10 years posttransplantation, three with insulin-dependent diabetes, who developed multiple areas of squamous cell carcinoma (SCC) in situ. All these patients were on chronic immunosuppressive chemotherapy to prevent rejection, but were otherwise doing well. All the patients had biopsy-proven SCC in situ on their lower extremities that even in normal patients may be a challenge to treat. RESULTS: We treated these five patients with a combination of a local immune therapy, imiquimod cream, and a topical chemotherapeutic agent, 5% 5-fluorouracil (5-FU), with clearing of the areas of SCC in situ. CONCLUSION: Although immunotherapy must be used with caution in organ transplant patients to avoid graft rejection, topical imiquimod is a local immune modulator that potentiates local innate and possible adaptive immunity without measurable effects on systemic immunity. In addition, there is evidence that cytokines induced by imiquimod may improve the therapeutic efficacy of topical 5% 5-FU in the treatment of SCC in situ.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11442593&dopt=Abstract imiquimod Aldara



Aldara
Development of a topically active imiquimod formulation.

Chollet JL, Jozwiakowski MJ, Phares KR, Reiter MJ, Roddy PJ, Schultz HJ, Ta QV, Tomai MA.

3M Pharmaceuticals, St. Paul, Minnesota, USA.

The purpose of this work was to develop a topical formulation of imiquimod, a novel immune response modifier, to induce local cytokine production for the treatment of external genital and perianal warts. A pH-solubility profile and titration data were used to calculate a pKa of 7.3, indicative of a weak base. Solubility experiments were conducted to identify a solvent that dissolves imiquimod to achieve a 5% formulation concentration. Studies to select surfactants, preservatives, and viscosity-enhancing excipients to formulate an oil-in-water cream indicated that fatty acids were the preferred solvent for topical imiquimod formulations, and isostearic acid (ISA) was selected. A relationship existed between the fatty acid composition of four commercially available ISA sources and the solubility of imiquimod. A combination of polysorbate 60, sorbitan monostearate, and xanthan gum was used to produce a physically stable cream. The preservative system included parabens and benzyl alcohol to meet the USP criteria for preservative activity. An in vitro method was developed to demonstrate that imiquimod was released from the formulation. Topical application of the formulation induced local cytokine activity in mice.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10027211&dopt=Abstract imiquimod Aldara



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Imiquimod-elicited emesis is mediated by the area postrema, but not by direct neuronal activation.

Strominger NL, Brady R, Gullikson G, Carpenter DO.

Albany Medical College, Albany, NY 12208, USA. stromin mail.amc.edu

The immunomodulator, imiquimod, has been shown to have antiviral and antitumor properties in animal models. It also has been reported to alter cytokine levels in both animals and humans. However, because imiquimod appeared to be emetic, studies were conducted to determine the degree of sensitivity, and the pathways involved. Subcutaneous administration of > or = 10 mg/kg imiquimod to ferrets elicited emesis with latencies as short as 2'; 12 and 15 mg/kg were optimal doses. Emetic responsiveness was eliminated by complete ablation of the area postrema, but was unaffected by bilateral supradiaphragmatic section of the vagus nerve. This indicates that the emesis is produced by an activation of the chemoreceptor trigger zone B the area postrema. Ferret brain stem slices (450 microm) were preincubated in oxygenated Krebs-Ringer and then mounted in a submerged slice recording chamber. Extracellular recordings of spontaneous and ionophoretically evoked activity of area postrema neurons were obtained for up to 8 h, while the effect of bath-applied imiquimod was determined. Under control conditions, neurons showed a low frequency spontaneous discharge. Introduction of imiquimod (concentration range, 1 x 10(-7) to 5 x 10(-8)M) had no effect on neuronal firing. With ionophoresis of glutamate from an independent micropipette, a brief excitatory response was obtained. We conclude that imiquimod does not directly excite area postrema neurons. It is likely that imiquimod causes synthesis and release of some unknown emetic substance(s), very possibly cytokines.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11489353&dopt=Abstract imiquimod Aldara



Aldara
New patient-applied therapy for anogenital warts is rated favourably by patients.

O'Mahony C, Law C, Gollnick HP, Marini M.

Department of Genito-Urinary Medicine, The Countess of Chester Hospital, Countess of Chester Health Park, Liverpool Road, Chester CH2 1UL, UK. dr.o'mahony coch-tr.nwest.nhs.uk

Our objective was to determine patient attitudes to having genital warts, and their perceptions of their treatment with imiquimod and other therapies. As an adjunct to a clinical trial in which patients with external genital warts were treated with imiquimod 5% cream until their warts cleared or for up to 16 weeks, quantitative questionnaires consisting of multiple choice questions and 5-point rating scales were completed prior to, and at the end, of the study period. Pre-study and post-study questionnaires were completed by 902 and 629 patients, respectively. Patients expressed a definite concern about genital warts. The majority of patients (70%) had been previously treated for genital warts, and expressed dissatisfaction with their previous therapies. Of patients treated with imiquimod in this study, 82% reported that their warts decreased in size; this occurred within the first 4 weeks for 78% of patients. Sixty-one per cent of patients perceived that their warts completely cleared within the 16-week treatment period. Patients rated imiquimod 5% cream as better than other genital wart therapies in terms of overall satisfaction, time to clearance, convenience and lack of associated pain. In conclusion, patients rated imiquimod 5% cream as an effective treatment which clears warts in an acceptable length of time causing minimal pain and is convenient to use.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11516364&dopt=Abstract imiquimod Aldara