Aldara
Innovative uses of imiquimod.

Vender RB, Goldberg O.

McMaster University, Hamilton, Ontario, Canada. drvender dermatrials.com

Imiquimod (Aldara, 3M Pharmaceuticals) is a potent stimulator of the innate and adaptive arms of the immune system through induction, synthesis, and release of cytokines and chemokines. An extensive review of clinical trials, case reports, and letters published in peer-reviewed journals was performed regarding imiquimod use in skin disorders. A reference module was developed for physicians to consult as a guide. Studies have validated the benefit of imiquimod in treating external genital and perianal warts, superficial basal cell carcinomas, and actinic keratoses. This new topical therapeutic agent has shown to be of benefit in other various skin disorders through its broad immunomodulatory properties. Since many skin conditions are immunologically influenced, it is reasonable to expect several diseases to respond to imiquimod. Our research consolidates the therapeutic trials and reports on the innovative uses of imiquimod, thereby serving as a useful resource to benefit dermatologists treating patients with refractory or recalcitrant skin diseases.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15696986&dopt=Abstract imiquimod Aldara



Aldara
Multiple basal cell carcinomas in a young adult treated with imiquimod 5%: a case report and literature review.

Bergman A, Contard P, Spencer J.

We present a case of basal cell carcinoma that is unique in the literature with regard to the rare combination of age of onset and number of BCCs at initial presentation that was successfully treated with imiquimod 5%. The patient is a 28-year-old Caucasian man with no past medical or dermatological history. Physical exam was remarkable for seven pink translucent skin lesions on the forehead, alar ridge, zygoma, and upper back. There were no signs or symptoms of a syndrome or disease entity known to cause BCC. Shave biopsies revealed basal cell carcinoma in all 7 lesions. The patient was successfully treated with topical imiquimod 5% 6 days per week for 6 weeks. The presentation of this number of de novo BCCs in a patient this young in absence of a known BCC syndrome has, to the best of our knowledge, not previously been reported in the literature and was successfully treated with imiquimod 5%.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15696993&dopt=Abstract imiquimod Aldara



Aldara
Multiple superficial basal cell carcinomata--topical imiquimod versus curette and cryotherapy.

Dixon AJ.

Skincanceronly, Geelong, Victoria. anthony skincanceronly.com

BACKGROUND: Superficial basal cell carcinoma can be successfully managed by means other than surgical excision. Nonexcisional approaches include topical imiquimod, and curette and cryotherapy (C&C). OBJECTIVE: This article discusses the management of an insulin dependent diabetic man aged 52 years presenting with 17 torso basal cell carcinomas (BCCs); mostly superficial BCCs (SBCCs). DISCUSSION: Half were treated with topical imiquimod. The remaining lesions were treated with curette and cryotherapy. All lesions resolved with proven histologic clearance. The patient considered C&C caused him less discomfort and disruption. He developed a late secondary infection in some sites treated with imiquimod. At 12 months there was no evidence of recurrence though new nodular BCCs and SBCCs had developed elsewhere on his upper torso. He has elected to have future SBCCs managed with C&C. While excisional surgery remains the benchmark management for nonmelanoma skin cancer, topical imiquimod and C&C are important options for treating SBCCs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15727358&dopt=Abstract imiquimod Aldara



Aldara
The cost effectiveness of patient-applied versus provider-administered intervention strategies for the treatment of external genital warts.

Langley PC, Tyring SK, Smith MH.

University of Colorado Health Sciences Center, Denver, USA. paul.langley UCHSC.edu

OBJECTIVE: External genital warts are one of the fastest growing sexually transmitted diseases in the United States today. Two forms of therapy are available: provider-administered and patient-applied. In the most widely used provider-administered ablative therapies, sustained clearance rates range from 18.5% to 40.1%. With nonablative, patient-applied therapies, which are typically more acceptable to patients, sustained clearance rates range from 19.6% with podofilox gel to 44.0% with imiquimod cream. The purpose of this study, given the range of therapies available, their cost differences, and clinical trial-reported differences in rates of sustained clearance, is to determine which therapy modalities, from the providers' perspective, are the most cost effective and which are likely to be the most acceptable to the patient population. STUDY DESIGN: We consider the cost effectiveness of the two patient-applied therapies as first-line therapy followed by provider-administered ablative treatment as second-line therapy. A decision-analytic model framework is developed, with data drawn both from clinical trials and from previously published studies. RESULTS: When considering a two-stage therapy model, with an average sustained clearance rate of 30% assumed for provider-administered ablative therapies, estimated costs per sustained cleared patient are $1265 for patients initially treated with imiquimod and $1304 for patients initially treated with podofilox gel. CONCLUSIONS: Initial treatment with imiquimod is the preferred intervention option as it yields a 39% greater sustained clearance rate than podofilox gel while being 3% less costly per successful outcome.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10345969&dopt=Abstract imiquimod Aldara



Aldara
Adjuvant activities of immune response modifier R-848: comparison with CpG ODN.

Vasilakos JP, Smith RM, Gibson SJ, Lindh JM, Pederson LK, Reiter MJ, Smith MH, Tomai MA.

Department of Pharmacology, 3M Pharmaceuticals, St. Paul, Minnesota 55144, USA.

R-848 and imiquimod belong to a class of immune response modifiers that are potent inducers of cytokines, including IFN-alpha, TNF-alpha, IL-12, and IFN-gamma. Many of these cytokines can affect the acquired immune response. This study examines the effects of R-848 on aspects of acquired immunity, including immunoglobulin secretion, in vivo cytokine production, and Ag-specific T cell cytokine production. Results are compared with those of Th1 CpG ODN. R-848 and CpG ODN are effective at skewing immunity in the presence of Alum toward a Th1 Ab response (IgG2a) and away from a Th2 Ab response (IgE). R-848 and CpG ODN are also capable of initiating an immune response in the absence of additional adjuvant by specifically enhancing IgG2a levels. Both R-848 and imiquimod showed activity when given subcutaneously or orally, indicating that the compound mechanism was not through generation of a depot effect. Although CpG ODN behaves similarly to R-848, CpG ODN has a distinct cytokine profile, is more effective than R-848 when given with Alum in the priming dose, and is active only when given by the same route as the Ag. The mechanism of R-848's adjuvant activity is linked to cytokine production, where increases in IgG2a levels are associated with IFN-alpha, TNF-alpha, IL-12, and IFN-gamma induction, and decreases in IgE levels are associated with IFN-alpha and TNF-alpha. Imiquimod also enhances IgG2a production when given with Ag. The above results suggest that the imidazoquinolines R-848 and imiquimod may be attractive compounds for use as vaccine adjuvants and in inhibiting pathological responses mediated by Th2 cytokines. Copyright 2000 Academic Press.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11006019&dopt=Abstract imiquimod Aldara



Aldara
Inhibition of murine tumor growth by an interferon-inducing imidazoquinolinamine.

Sidky YA, Borden EC, Weeks CE, Reiter MJ, Hatcher JF, Bryan GT.

Cancer Center, Medical College of Wisconsin, Milwaukee 53226.

The low-molecular-weight imidazoquinolinamine derivative, 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (imiquimod, previously described as R-837), induced alpha-interferon (IFN-alpha) in mice. IFN induction was identified at oral doses as low as 3 mg/kg. The 10% lethal dose for daily treatment with imiquimod was 200 mg/kg. Oral treatment with 30 mg/kg imiquimod once every three days significantly inhibited MC-26 colon carcinoma. Delay of treatment from day 1 to day 5, when tumors were easily palpable, did not reduce benefits. Ten daily treatments were slightly more effective than five. However, delivery of the same total dose of imiquimod either once every day for 20 days, once every 4 days, once every 7 days, or once every 10 days inhibited tumor growth to the same level. The antitumor effects of imiquimod were significantly abrogated by an antiserum to murine IFN-alpha, suggesting that the antitumor effect was to a substantial extent mediated by IFN induction. Imiquimod also significantly reduced the number of lung colonies in mice inoculated i.v. with MC-26 tumor cells. Combination of treatment with imiquimod and cyclophosphamide was significantly (P less than 0.01) better than treatment with either drug alone. Combination treatment with cyclophosphamide led to cures in some of the mice inoculated either s.c. or i.v. with MC-26 cells. Treatment with imiquimod also inhibited the growth of RIF-1 sarcoma and Lewis lung carcinoma but was ineffective for P388 leukemia. Imiquimod is an oral IFN-alpha inducer with antitumor effectiveness for transplantable murine tumors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1377595&dopt=Abstract imiquimod Aldara