Imiquimod 5% cream for the treatment of superficial and nodular basal cell carcinoma: randomized studies comparing low-frequency dosing with and without occlusion

BACKGROUND: Imiquimod 5% cream has been investigated for non-surgical treatment of superficial and nodular basal cell carcinoma (BCC) tumours. OBJECTIVES: Two studies were conducted to examine the effect of occlusion at low dosing frequencies on the safety and efficacy of topical imiquimod 5% cream for the treatment of superficial and nodular BCC. PATIENTS AND METHODS: Both open-label studies were conducted in Europe. Patients diagnosed with BCC were enrolled into either the superficial (93 patients) or nodular (90 patients) study, depending on the histological confirmation of the patient's tumour subtype. Patients were randomized to one of four groups to apply imiquimod 5% cream 2 or 3 days per week either with or without occlusion. Six weeks following a 6-week treatment period, the entire target tumour area was excised and histologically examined for evidence of residual tumour. RESULTS: In both studies, the highest histologically complete response rate was seen in the 3 days per week with occlusion groups, with complete response rates of 87% and 65% for the superficial and nodular studies, respectively. Occlusion did not have a statistically significant effect on response rate at either dosing frequency. Response rates for superficial and nodular BCC tumours treated 3 days per week without occlusion were 76% and 50%, respectively. CONCLUSIONS: In the superficial study, the complete response rate of 87% in the 3 days per week with occlusion group was similar to that of daily and 5 days per week dosing without occlusion in a previous 12-week study and one study of daily dosing without occlusion for 6 weeks. All treatment groups had acceptable safety profiles in both studies. Occlusion did not have a statistically significant effect on efficacy for either superficial or nodular BCC tumours.     

Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: a double-blind,randomized, vehicle-controlled study

BACKGROUND: Imiquimod 5% cream may provide an effective nonsurgical treatment for superficial basal cell carcinoma (sBCC) based on results of previous studies. OBJECTIVE: The objective of this phase II dose-response study was to explore various dosing regimens using imiquimod 5% cream for sBCC to find the most effective frequency of dosing with tolerable side effects. METHODS: Patients (n = 128) were dosed twice daily, once daily, 5 times a week, or 3 times a week in this 12-week, randomized, double-blind, vehicle-controlled study. At 6 weeks after treatment, the entire tumor area was clinically evaluated, excised, and examined exhaustively for histologic evidence of residual sBCC. RESULTS: Complete response rates were 100% (10/10), 87.1% (27/31), 80.8% (21/26), and 51.7% (15/29) for patients in the twice daily, once daily, 5 times a week, and 3 times a week imiquimod groups, respectively, and 18.8% (6/32) in the vehicle group. CONCLUSION: Imiquimod 5% cream was effective in the treatment of sBCC. Daily or 5 times a week dosing for 12 weeks demonstrated high efficacy results with acceptable safety profiles.     

Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies

BACKGROUND: Imiquimod is an immune response modifier that is a Toll-like receptor 7 agonist that induces interferon and other cytokines through the innate immune system and stimulates cell-mediated immunity through T cells. Imiquimod has been shown to be efficacious as a topical treatment for basal cell carcinoma (BCC). OBJECTIVE: We sought to evaluate the efficacy and safety of imiquimod 5% cream compared with vehicle for treating superficial BCC (sBCC). METHODS: Two identical studies were conducted. Subjects with one sBCC were dosed with imiquimod or vehicle cream once daily 5 or 7x/week for 6 weeks in these 2 randomized, double-blind, vehicle-controlled Phase III studies. The lesion site was clinically examined 12 weeks posttreatment and then excised for histological evaluation. RESULTS: Data from both studies were pooled. Composite clearance rates (combined clinical and histological assessments) for the 5 and 7x/week imiquimod groups were 75% and 73%, respectively. Histological clearance rates for the 5 and 7x/week imiquimod groups were 82% and 79%, respectively. Increasing severity of erythema, erosion, and scabbing/crusting was associated with higher clearance rates. CONCLUSION: Imiquimod appears to be safe and effective for the treatment of sBCC when compared with vehicle cream. The difference in clearance rates between the two imiquimod dosing groups was not significant. The 5x/week regimen is recommended.     

Imiquimod: in superficial basal cell carcinoma

Imiquimod, 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 in superficial BCC is unknown. Imiquimod 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. Topical imiquimod 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 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. In a trial investigating the long-term efficacy of imiquimod 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%. Application site and local skin reactions were the most common adverse events reported by imiquimod recipients. The severity of erythema, erosion, and scabbing/crusting correlated positively with the composite and histologic response rates.     

Imiquimod

? Imiquimod, 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 in superficial BCC is unknown. Imiquimod 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. ? Topical imiquimod 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 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. ? In a trial investigating the long-term efficacy of imiquimod 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%. ? Application site and local skin reactions were the most common adverse events reported by imiquimod recipients. The severity of erythema, erosion, and scabbing/crusting correlated positively with the composite and histologic response rates.     

Therapeutic response of basal cell carcinoma to the immune response modifier imiquimod 5% cream

BACKGROUND: Basal cell carcinoma (BCC) responds to interferon therapy. Imiquimod is a cytokine and interferon inducer. OBJECTIVE: This randomized, double-blind pilot trial evaluated the safety and efficacy of imiquimod 5% cream versus vehicle in the treatment of BCC. METHODS: In this population of 35 patients with BCC, 24 received imiquimod 5% cream and 11 received vehicle cream in 1 of 5 dosing regimens for up to 16 weeks. Six weeks after treatment, an excisional biopsy of the target site was performed. RESULTS: BCC cleared (on the basis of histologic examination) in all 15 patients (100%) dosed twice daily, once daily, and 3 times weekly; in 3 of 5 (60%) patients dosed twice weekly; 2 of 4 (50%) dosed once weekly; and in 1 of 11 (9%) treated with vehicle. Adverse events were predominantly local reactions at the target tumor site, with the incidence and severity of local skin reactions declining in groups dosed less frequently. CONCLUSION: Imiquimod 5% cream shows clinical efficacy in the treatment of BCC.     

Imiquimod 5% cream in the treatment of superficial basal cell carcinoma: results of a multicenter 6-week dose-response trial

BACKGROUND: Superficial basal cell carcinoma (sBCC) is an increasingly common tumor in fair-skinned populations throughout the world. Imiquimod, an immune response modifier that induces cytokines including interferons, has been shown in preliminary studies to have an effect when applied topically to BCC. OBJECTIVE: We conducted a multicenter, randomized, open-label dose-response trial of imiquimod 5% cream in the treatment of primary sBCC assessing efficacy and safety of different dose regimens. METHODS: Ninety-nine patients were randomized to 6 weeks' application of imiquimod in 1 of 4 treatment regimens: twice every day, once every day, twice daily 3 times/week, once daily 3 times/week. The treatment site was excised and examined histologically 6 weeks after cessation of imiquimod. RESULTS: Intention-to-treat analysis revealed 100% (3/3) histologic clearance in the twice-daily regimen, 87.9% (29/33) clearance in the once every day regimen, 73.3% (22/30) clearance in the twice-daily 3 times/week regimen, and 69.7% (23/33) clearance in the once-daily 3 times/week regimen. Dose-related inflammatory skin reactions at the site of application were common. The majority were well tolerated and only 1 patient withdrew from the trial as a result of a medication-related skin reaction. CONCLUSION: Imiquimod 5% cream appears to have potential as a patient-administered treatment option in sBCC.     

Recurrence rate of superficial basal cell carcinoma following successful treatment with imiquimod 5% cream: interim 2-year results from an ongoing 5-year follow-up study in Europe

Imiquimod is an immune response modifier that acts through Toll-like receptor 7 to induce innate and cell-mediated immune responses. This ongoing phase III, open-label study conducted in Europe is evaluating the long-term (5 year) clinical efficacy and safety of imiquimod 5% cream applied once daily 5 times per week (5 x/week) for 6 weeks for the treatment of superficial basal cell carcinoma (sBCC). A total of 182 subjects were enrolled. The initial sBCC clearance rate was 90% (12-week post treatment), whereas the proportion of subjects who were clinically clear at 2 years (current time point) was estimated to be 79.4%. Local skin/application site reactions were the most frequently reported safety findings. Initial efficacy rates of imiquimod applied 5 x/week for 6 weeks demonstrate its clinical utility as an alternative approach to the treatment of sBCC. The recurrence rate seen to date supports ongoing follow up of subjects treated with imiquimod.     

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

BACKGROUND: Imiquimod 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 5% cream. OBJECTIVES: To evaluate the safety and clinical efficacy of imiquimod (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 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 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 and vehicle cream, respectively. Histological clearance was demonstrated in 80% and 6% of subjects treated with imiquimod 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 group than in the vehicle group. CONCLUSIONS: Imiquimod 5% cream administered 7 x/week for 6 weeks is a safe and effective treatment for sBCC when compared with vehicle cream.     

Effect of dosing frequency on the safety and efficacy of imiquimod 5% cream for treatment of actinic keratosis on the forearms and hands: a phase II, randomized placebo-controlled trial

Background  Clinical studies in cutaneous conditions other than actinic keratosis (AK) have revealed that the safety and efficacy profile of imiquimod is influenced by dosing frequency.
Objectives  To evaluate dosing frequency response of imiquimod 5% for treatment of AK.
Methods  This was a phase II, multicentre, randomized, double-blind, placebo-controlled study. Adults with ≥ 10 but ≤ 50 clinical AKs, one of which was histologically confirmed, were randomized (4 : 1) to 2–6 packets of imiquimod or placebo cream applied to the dorsum of the forearms and hands once daily 2, 3, 5 or 7 times per week for 8 weeks. The primary endpoint was complete clearance of AKs in the treatment area at 8 weeks post-treatment.
Results  One hundred and forty-nine (94 men and 54 women) white subjects, with a mean ± SD age of 71 ± 10·2 years, were enrolled. Twenty-eight subjects (18·8%) discontinued from study: 0%, 3·1%, 6·9%, 30·0% and 33·3% withdrew for local skin reactions or adverse events in the combined placebo, and in the imiquimod 2, 3, 5 or 7 times per week groups, respectively. Seven serious adverse events occurred; none was related to the study drug. Median baseline lesions ranged from 38 to 40 for the treatment groups. Complete clearance was achieved in 0%, 3·2%, 6·9%, 3·3% and 6·7% of subjects, and partial clearance (≥ 75% lesion reduction) in 0%, 22·6%, 24·1%, 20·0% and 36·7% of subjects for the placebo and imiquimod 2, 3, 5 or 7 times per week regimens, respectively.
Conclusions  Imiquimod 5% applied more frequently than 3 times per week to AKs was not well tolerated. Complete clearance rates were low; however, partial clearance rates increased with increased dosing frequency ( P  =   0·002).     

Open study of the efficacy and mechanism of action of topical imiquimod in basal cell carcinoma

Imiquimod is an immune-response modifier that has been shown to be effective in the treatment of superficial and nodular basal cell carcinoma (BCC). The objective of this open-label study was to investigate the effectiveness of imiquimod 5% cream in superficial, nodular, and infiltrative BCC. Fifty-five Caucasian patients with primary BCC measuring 8 mm or more in diameter with a superficial, nodular, or infiltrative histological pattern were included in the study. Four groups of BCC (A, B, C, and D) and two dosing regimens were studied: 35 BCCs (groups A, B, and C) were treated with imiquimod three times weekly and 20 BCCs (group D) were treated with imiquimod five times weekly. Histological samples were obtained before treatment, during treatment (on day 22 in group A, day 15 in group B, and day 8 in groups C and D), and 6 weeks after treatment. All patients were followed-up for a minimum of 2 years. In the biopsy specimens obtained, the expression of Bcl-2, p53, and Ki-67, apoptotic index (Tunel technique), and the number of CD3+, CD8+, CD20+, CD56+, CD68+, granzyme B+, and S-100+ cells in the peritumoural inflammatory infiltrate, were determined and quantified. Of the 55 BCCs treated with imiquimod 41 (74%) were in complete remission after 2 years of follow-up. These comprised 4/4 superficial BCCs, 7/8 (88%) nodular BCCs, and 30/43 (70%) infiltrative BCCs. Multi-variate analysis demonstrated that baseline tumour size was the most powerful independent prognostic variable (P < 0.05). Treatment with imiquimod increased the apoptotic index (P < 0.05), reduced Bcl-2 expression (P < 0.05), and increased the number of CD3+, CD8+, CD20+, CD68+, granzyme B+, and S-100+ cells in the inflammatory infiltrate of the BCC (P < 0.05). In conclusion, imiquimod induced an antitumour immune response mediated by lymphocytes and macrophages, reduced Bcl-2 expression and increased the apoptotic index of BCC, and was clinically effective in 74% of BCCs after a 2-year follow-up period.     

A randomized,double-blind,vehicle-controlled study to assess 5% imiquimod cream for the treatment of multiple actinic keratoses

BACKGROUND: Actinic keratoses (AKs) are precancerous epidermal lesions found most frequently on areas of the skin exposed to the sun. Several case studies published recently have indicated that 5% imiquimod cream, currently licensed for the treatment of genital warts, may be an effective treatment for AK. OBJECTIVE: To assess the efficacy and safety of imiquimod for the treatment of AK. DESIGN: Patients in this randomized, double-blind, vehicle-controlled study applied 5% imiquimod cream or vehicle to AK lesions 3 times per week for a maximum of 12 weeks or until lesions had resolved. In the event of an adverse reaction, application of imiquimod was reduced to 1 or 2 times per week. Rest periods were also allowed if necessary. SETTING: A specialized outpatient dermatology clinic within a state-funded hospital in Germany. PATIENTS: The study population was aged 45 to 85 years. Of 52 patients screened, 36 men and women with AK confirmed by histological diagnosis were enrolled. Patients were excluded from the study if they did not have a histological diagnosis for AK, if they were older than 85 years, or if they did not comply with the protocol. All patients had responded to a notice asking for volunteers. MAIN OUTCOME MEASURES: The number and appearance of lesions were evaluated before, during, and after treatment. All adverse effects were recorded. RESULTS: Lesions treated with 5% imiquimod cream were clinically cleared in 21 (84%) of 25 patients and partially cleared in 2 (8%). Clearance was histologically confirmed 2 weeks after the last application of imiquimod in all patients clinically diagnosed as lesion free. Only 10% of patients treated with imiquimod were clinically diagnosed with recurrence 1 year after treatment. No reduction in the size or number of AK lesions was observed in vehicle-treated patients. Adverse effects reported by patients treated with imiquimod included erythema, edema, induration, vesicles, erosion, ulceration, excoriation, and scabbing. However, imiquimod was well tolerated since all patients completed the 12-week treatment. Only a few, mild adverse reactions to the vehicle cream were reported. CONCLUSION: Application of 5% imiquimod cream for 12 weeks is an effective and well-tolerated treatment for AK.     

Treatment of external genital warts in men using 5% imiquimod cream applied three times a week, once daily, twice daily, or three times a day

BACKGROUND: Medical therapy for genital warts remains suboptimal. The topical interferon and cytokine inducer, imiquimod, has been proved effective for the treatment of external genital and perianal warts, but there is a substantial difference in the response rates between men and women. When 5% imiquimod cream is applied three times a week up to 16 weeks, approximately two thirds of women treated with imiquimod achieve complete clearance of genital warts, whereas only about one third of men clear completely. GOAL: This study was undertaken to determine whether more frequent application of topical imiquimod cream would improve the rate of genital wart clearance in men. STUDY DESIGN: A randomized treatment trial involving adult men with biopsy-proven genital warts was conducted at nine centers in the United States and Canada using four different application frequencies. RESULTS: Complete clearance rates during the 16-week treatment period were as follows for the different imiquimod treatment frequencies: three times a week (35 %), once daily (28 %), twice daily (24%), and three times a day (27%)(P = 0.88). The four treatment groups all showed comparable reductions in the total lesion area, with a median of more than a 90% reduction in the lesion area by the end of treatment. There was a significant increase in the incidence and severity of local skin reactions including erythema, vesicle formation, ulceration, and excoriation as the dosing frequency increased from three times a week to three times a day. CONCLUSIONS: In this study, the optimal dosage regimen was the approved three times a week regimen. More frequent application (up to three times a day) did not improve clearance and was associated with an increase in local adverse events.     

Imiquimod 5% cream is an acceptable treatment option for external anogenital warts in uncircumcised males

OBJECTIVES: To determine the safety and efficacy of imiquimod (Aldara) 5% cream in the treatment of prepuce-associated warts in uncircumcised males. METHODS: An open-label study in six UK medical centres with 35 uncircumcised males with prepuce-associated warts treated with imiquimod 5% cream three times per week for up to 16 weeks. Other anogenital warts were also treated. RESULTS: Three times weekly application of imiquimod was found to be safe, with erythema as the most commonly reported local skin reaction. Forty per cent of patients had complete clearance of anogenital warts within 16 weeks. CONCLUSIONS: Imiquimod cream at a dosing regimen of three times per week, is effective and has an acceptable safety profile in the treatment of prepuce associated warts and other external anogenital warts in uncircumcised males.     

Pharmacokinetics of imiquimod 3.75% cream applied daily for 3 weeks to actinic keratoses on the face and/or balding scalp

Imiquimod 3.75% cream is a topical formulation of imiquimod intended for daily application to treat actinic keratoses of the entire face or balding scalp. The objective of the study was to characterize serum imiquimod and metabolite pharmacokinetics. Nineteen subjects with actinic keratoses applied two packets of imiquimod 3.75% cream (18.75 mg imiquimod total) once daily for 21 days to a treatment area approximately 200 cm² in size on the face and/or balding scalp. Blood samples were obtained prior to application of doses 1, 7, 14 and 21, and at selected timepoints after application of doses 1 and 21. After multiple dosing (day 21) serum imiquimod mean C _max was 0.323 (standard deviation 0.159) ng/mL, mean AUC(0-24) 5.974 (3.088) ng h/mL, and mean T½ 29.3 (17.0) h. Steady-state was achieved by day 14; multiple dose accumulation ratios were 2.8 based on imiquimod C _max and 3.9 based on AUC. Serum concentrations of imiquimod metabolites were only sporadically quantifiable in three subjects. One subject discontinued from study for adverse events of body aches and fatigue that were attributed to study drug. Treatment-related adverse events occurred in 42.1% (8/19) of the subjects. Systemic imiquimod exposure, as reflected by serum drug concentration, was low after daily application of two packets of imiquimod 3.75% cream for 21 days. Steady state was achieved by day 14, and the observed half-life of approximately 29 h supports daily dosing of the product.     

Use of 5% imiquimod cream in the treatment of facial basal cell carcinoma: a 3-year retrospective follow-up study

There has been considerable research into the safety and efficacy of topical 5% imiquimod cream for the treatment of skin cancers in recent years, in particular superficial and nodular basal cell carcinomas. However, there are limited long-term follow-up studies. This retrospective study aims to determine the efficacy of 5% imiquimod cream in the treatment of facial basal cell carcinomas over 3 years. Medical records of 12 patients treated with 5% imiquimod cream at a private dermatology practice during 2001 and 2002 were retrospectively reviewed. Target tumours included superficial and nodular basal cell carcinomas, giving a total lesion number of 19. Patients were commenced on a once daily treatment regimen for up to 9 weeks, and given rest periods as required according to the severity of application site reactions. We found that 5% imiquimod cream is an effective treatment option for superficial and nodular basal cell carcinomas, giving a clearance rate of 89.5% at an average of 39 months of follow up.     

Imiquimod 5% cream as pretreatment of Mohs micrographic surgery for nodular basal cell carcinoma in the face: a prospective randomized controlled study

Background Imiquimod 5% cream can reduce or clear superficial and small nodular basal cell carcinoma (BCC). It could be used as a pretreatment of Mohs micrographic surgery (MMS) to decrease defect size. Objectives To study if a pretreatment with imiquimod 5% cream decreases defect size after MMS. In addition, to study the effect on the number of Mohs stages and reconstruction time. Methods Seventy patients aged >18 years with a primary nodular BCC in the face were included. The imiquimod group used imiquimod 5% cream for 4 weeks, before MMS. The control group was treated with MMS only. Tumour and defect sizes were measured. We noted the number of Mohs stages, reconstruction time and side‐effects. Results The median percentage increase in area from tumour size at baseline to the post‐MMS defect for the imiquimod group was significantly less compared with the control group, 50% vs. 147% (P < 0·001). A tendency towards fewer Mohs stages in the imiquimod group was observed and the reconstruction time was significantly shorter in this group (P = 0·01). Conclusions Imiquimod 5% cream as pretreatment of MMS significantly reduced the tumour size in primary nodular BCC and reduced the surgical defect size. Further research is necessary to investigate cost‐effectiveness.     

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

OBJECTIVE: To evaluate the efficacy and safety of 5% imiquimod cream compared with vehicle in the treatment of actinic keratosis (AK). DESIGN: Two phase 3 randomized, double-blind, parallel-group, vehicle-controlled studies. SETTING: Twenty-six ambulatory care offices, including dermatologists in private practice or research centers. PATIENTS: 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. INTERVENTIONS: 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. MAIN OUTCOME MEASUREMENTS: 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. RESULTS: 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. CONCLUSION: The 5% imiquimod cream dosed 3 times weekly for 16 weeks is safe and effective for the treatment of AK.     

Pharmacokinetics and safety of imiquimod 5% cream in the treatment of molluscum contagiosum in children

Abstract:  Imiquimod cream 5%, a toll-like receptor 7 agonist, induces α-interferon upon topical application, prompting off-label usage to treat children with molluscum contagiosum. We conducted an open-label study to measure serum drug concentration in children aged 2–12 years with extensive molluscum contagiosum (≥10% total body surface area). Dependent on extent of subject disease and weight, one to three packets (12.5 mg imiquimod per packet) were applied per dose, three times per week for 4 weeks. Serum imiquimod and metabolite concentrations were measured at pre dose and 2, 4, and 8 hours postdose 1 and dose 12. Thirty children were screened; 22 children (64% boys; 91% white; mean age 6.2 ± 2.87 years; median involved body area treated 13.5%) were enrolled. Peak serum imiquimod concentrations following single and multiple dosing were low (<10 ng/mL). Imiquimod concentrations increased 2- to 3.5-fold with multiple dosing. After single and multiple dosing, peak serum imiquimod (Pearson correlation r  = 0.4989 and 0.7219, p < 0.05 both, respectively) and area under the serum concentration-time curve values ( r  = 0.4989 and 0.7219, p < 0.05 both, respectively) correlated with dose normalized for body weight (mg/kg). Systemic drug levels were low after single and multiple doses of imiquimod 5% cream in children.