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 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.     

Recurrence rate of superficial basal cell carcinoma following treatment with imiquimod 5% cream: conclusion of a 5-year long-term follow-up study in Europe

Imiquimod 5% cream is an immune response modifier approved for the treatment of superficial basal cell carcinoma (sBCC) once daily, 5 x per week for 6 weeks. This report reveals the final results of a 5-year follow-up study to evaluate the recurrence rate of sBCCs treated with imiquimod. As previously reported, 182 patients were enrolled in the study and 163 (89.6%) had no clinical evidence of their target sBCC at the 12-week post-treatment assessment; these 163 were followed for up to 5 years. During the follow-up period, 18 clinical recurrences occurred at the target tumour site, 8 and 10 of which occurred during the first 6 and 12 months of follow-up, respectively. The 5-year Kaplan-Meier and life-table estimates for sustained clinical clearance of those patients initially cleared were 84.5% and 86.9%, respectively, and 90.3% considering histology. The estimate of overall treatment success for all treated patients at the end of follow-up was 77.9% (80.9% considering histology). The data support clinical assessment of initial response as predictive of long-term outcome. Most of the recurrences occurred early, indicating that careful follow-up is important during the first year after treatment.     

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

? 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: 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 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.     

Successful Treatment of Giant Basal Cell Carcinoma with Topical Imiquimod 5% Cream with Long Term Follow-up

The use of the topical Imiquimod 5% cream offers a noninvasive, nonsurgical, and an effective option for the treatment of primary small (<2 cm) superficial basal cell carcinoma (sBCC). However, reports about successful treatment of giant (>5 cm) BCC with topical Imiquimod 5% cream are rare. We present our experience in the treatment of two giant tumors (6 × 8 cm², 5.2 × 4.2 cm²) of BCC on the face with Imiquimod 5% cream, 2 to 3 days/week for 12 weeks. Both the tumors were cured with clinical and pathological evidence, one with 6-year follow-up and the other with 3.5-year follow-up.     

Efficacy of topical 5% imiquimod cream for the treatment of nodular basal cell carcinoma: comparison of dosing regimens

OBJECTIVE: To establish a safe and efficacious dosing regimen for the treatment of primary nodular basal cell carcinoma (BCC) using 5% imiquimod cream. DESIGN: Two phase 2 studies were conducted: a 6-week, randomized, open-label, dose-response study evaluating 4 dosing regimens and a 12-week, randomized, vehicle-controlled, double-blind, dose-response study evaluating 4 dosing regimens. SETTING: Twenty-four public and private dermatology clinics in Australia and New Zealand (6-week study) and the United States (12-week study) participated. PATIENTS: The study populations comprised 99 patients enrolled in the 6-week study and 92 patients in the 12-week study. Patients were at least 18 years old and had a biopsy-confirmed diagnosis of nodular BCC. INTERVENTIONS: In the 6-week study, imiquimod was applied once daily for 3 or 7 days per week or twice daily for 3 or 7 days per week. In the 12-week study, imiquimod or placebo cream (vehicle) was applied once daily for 3, 5, or 7 days per week, or twice daily for 7 days per week. The entire tumor area was excised 6 weeks after treatment and examined histologically for evidence of remaining BCC. MAIN OUTCOME MEASURE: The proportion of patients having no histologic evidence of BCC in the posttreatment excision specimen. RESULTS: Dosing once daily for 7 days per week resulted in the highest clearance rate, with 25 (71%) of 35 and 16 (76%) of 21 patients showing clearance of their tumor in the 6- and 12-week studies, respectively. CONCLUSIONS: Topical 5% imiquimod cream is well tolerated and most effective in treating nodular BCC when applied once daily for 7 days per week for either 12 or 6 weeks.     

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 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.     

Efficacy of imiquimod 5% cream for basal cell carcinoma in transplant patients

Imiquimod 5% cream has proven to be effective in superficial and nodular basal cell carcinomas in nonimmunosuppressed patients and treating squamous cell carcinomas in situ in transplant patients. The objective of this open-label study was to determine the efficacy of imiquimod 5% cream in treating basal cell carcinoma in transplant patients. At our unit, four renal transplant patients and one cardiac transplant patient were diagnosed with 10 basal cell carcinomas in 2001. Four tumours were superficial, three nodular and three infiltrative. Five basal cell carcinomas received imiquimod 5% cream at night four times weekly for 6 weeks, without occlusion, and the other five tumours were treated on 5 nights per week for 5 weeks. Biopsies taken 6 weeks after the end of treatment showed no tumour in seven of 10 of the cases. Notably, all four superficial basal cell carcinomas, two of the three of nodular lesions and one of the three of infiltrative cases had completely cleared.     

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.     

Superficial basal cell carcinoma on face treated with 5% imiquimod cream

Imiquimod, an immune response modifier, is known to possess both anti-viral and anti-tumor effect. We report our experience of treating a large superficial spreading basal cell carcinoma with 5% imiquimod cream. A 65-year-old male had an asymptomatic, hyperpigmented, slowly progressive, indurated, 3 x 4 cm plaque on the left cheek for two months. Biopsy from the lesion showed features of basal cell carcinoma. The patient was treated with imiquimod 5% cream, topically three times a week for six months with complete resolution of the lesion and without any side-effects. There was no clinical or histological recurrence after three months of stopping the treatment.     

Tratamiento de la enfermedad de Bowen con imiquimod 5% crema

Imiquimod is an immune modifier that has been shown to be effective for some skin cancer and precancer such as solar keratoses, basal cell carcinoma and Bowen's disease. It has been proved to have antiviral and antitumor properties in animal models. The biological pathway is closely related with the release of some cytokines, mainly interferon (INF)-α and tumoral necrosis factor (TNF)-α.A trial with imiquimod 5% cream, twice daily, three times a week, during 8 weeks was undertaken in 5 patients with biopsy-proven Bowen's disease. One patient had undergone a renal transplantation and was on chronic immunosupressive chemotherapy for 8 years. Lesions were located on the legs, hands and face. After treatment all lesions had cleared up, and in three patients clearance was histologically confirmed with a posttreatment biopsy. All patients complained of mild erythema and itching, but the treatment was well tolerated. Within follow-up periods of 3 to 11 months after treatment none has shown evidence of recurrence.Even though this is a short series of patients, we believe that imiquimod 5% cream is an effective and safe treatment for Bowen's disease at a shorter term than previously advised. Since Bowen's lesions were not fully excised at the end of the treatment, only a longer follow up of our patients will confirm their clearance.     

Multiple basal cell carcinomas in xeroderma pigmentosum treated with imiquimod 5% cream

Abstract:  We report successful treatment of multiple basal cell carcinomas with imiquimod 5% cream in a 16-year-old boy with xeroderma pigmentosum and review the possibility of prophylactic role of imiquimod in the disease. Imiquimod cream was applied uniformly over all the basal cell carcinoma lesions and background pigmented skin, once at bedtime on every alternate day for 12 weeks. Besides the basal cell carcinomas, the background hyperpigmentation and keratotic papules also cleared, and the skin texture improved. The lesions did not recur at the treated sites during the follow up of 1 year.     

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).     

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.     

Evaluation of recurrence after photodynamic therapy with topical methylaminolaevulinate for 157 basal cell carcinomas in 90 patients

The aim of this study was to evaluate the effect of photodynamic therapy with topical methylaminolevulinate for the treatment of basal cell carcinomas in a single dermatological department. Ninety patients (34.4% men and 65.6% women) with a total of 157 basal cell carcinomas (111 superficial, 40 nodular, 6 unknown) were treated. Primary endpoint was clinically observed recurrence verified by biopsy 3, 6 and 12 months after treatment, then once a year. Estimated patient recurrence rates were 7% at 3 months, 19% at 6 months, 27% at 12 months and 31% at 24 months. Patients aged over 60 years had significantly higher estimated recurrence rates compared with patients aged 60 years or under (at 12 months, 35% vs. 19%, p?=?0.01). Estimated recurrence rates for tumours was 4% at 3 months, 11% at 6 months, 16% at 12 months and 19% at 24 months. There were significantly higher estimated recurrence rates for nodular basal cell carcinomas compared with superficial basal cell carcinomas (at 12 months, 28% vs. 13%, p?=?0.008). In conclusion, photodynamic therapy is only appropriate for treatment of superficial basal cell carcinoma, and, age above 60 years and histology showing nodular basal cell carcinoma are independent risk factors for developing a recurrent basal cell carcinoma.     

Resolution of tinea pedis with imiquimod cream 5% in a patient with nodular basal cell carcinoma

A 73-year-old white man with nodular basal cell carcinoma (nBCC) of the toe and interdigital tinea pedis was treated with imiquimod cream 5% once daily for 4 weeks and twice daily for 10 weeks. Results of a posttreatment potassium hydroxide (KOH) preparation and biopsy confirmed clearance of both tinea pedis and nBCC, respectively.