Imiquimod 5% Cream for the Treatment of Superficial BCC
Imiquimod 5% Cream for the Treatment of Superficial BCC
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 (Aldara; 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 ×/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 ×/week for 6 weeks is a safe and effective treatment for sBCC when compared with vehicle cream.
Basal cell carcinoma (BCC), the most common malignancy in white people, has an incidence that is increasing worldwide by up to 10% annually. Subtypes of BCC include superficial, which occurs mainly on the trunk, nodular, morphoeic and pigmented. Exposure to ultraviolet radiation is the main environmental risk factor for the pathogenesis of BCC, and it tends to be associated with certain host risk factors (e.g. skin type I: always burns, never tans). BCCs seem to develop a number of defence mechanisms that block cell-mediated immunity (CMI). Imiquimod triggers transcription of interferon-α and other cytokines through activation of toll-like receptor 7 on antigen-presenting cells and has been shown to induce cellular changes consistent with activation of CMI. Therefore, it was postulated that imiquimod might be able to induce a CMI response competent enough to clear the tumour. Earlier clinical studies have supported this hypothesis by demonstrating imiquimod's efficacy in treating superficial BCC (sBCC). These studies have demonstrated that the once daily five times per week (5 ×/week) and seven times per week (7 ×/week) dosing regimens used for 12 weeks were the most promising for treating sBCC. Furthermore, a 7 ×/week dosing regimen has shown similar efficacy rates with a shorter treatment duration of 6 weeks. Based on this evidence, a dosing regimen of 7 ×/week for 6 weeks was chosen for this study. Common treatment-emergent side-effects are application site reactions (ASRs) (e.g. burning, itching and pain at the treatment site), as reported by the subjects, and local skin reactions (LSRs) (e.g. erythema, erosion, scabbing and crusting), assessed by the investigator as per a rating scale defined in the protocol. Typically, the frequency of these treatment-emergent effects increases as dosing frequency increases.
In cases where the tumour had cleared after imiquimod treatment, it is important to be confident that the correct area was located and assessed. The earlier studies had used a combination of anatomical drawings, photodocumentation and a plastic template marking skin landmarks in order to find the site of the original target tumour. In this phase III study, the aim was to compare the safety and efficacy of imiquimod (Aldara; 3M Pharmaceuticals, St Paul, MN, U.S.A.) 5% cream with vehicle cream applied 7 ×/week for 6 weeks for the treatment of sBCC in subjects whose tumours were marked with a central indelible mark before treatment initiation. Marking the tumours in this way further assures the validity of the efficacy measurement.
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 (Aldara; 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 ×/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 ×/week for 6 weeks is a safe and effective treatment for sBCC when compared with vehicle cream.
Basal cell carcinoma (BCC), the most common malignancy in white people, has an incidence that is increasing worldwide by up to 10% annually. Subtypes of BCC include superficial, which occurs mainly on the trunk, nodular, morphoeic and pigmented. Exposure to ultraviolet radiation is the main environmental risk factor for the pathogenesis of BCC, and it tends to be associated with certain host risk factors (e.g. skin type I: always burns, never tans). BCCs seem to develop a number of defence mechanisms that block cell-mediated immunity (CMI). Imiquimod triggers transcription of interferon-α and other cytokines through activation of toll-like receptor 7 on antigen-presenting cells and has been shown to induce cellular changes consistent with activation of CMI. Therefore, it was postulated that imiquimod might be able to induce a CMI response competent enough to clear the tumour. Earlier clinical studies have supported this hypothesis by demonstrating imiquimod's efficacy in treating superficial BCC (sBCC). These studies have demonstrated that the once daily five times per week (5 ×/week) and seven times per week (7 ×/week) dosing regimens used for 12 weeks were the most promising for treating sBCC. Furthermore, a 7 ×/week dosing regimen has shown similar efficacy rates with a shorter treatment duration of 6 weeks. Based on this evidence, a dosing regimen of 7 ×/week for 6 weeks was chosen for this study. Common treatment-emergent side-effects are application site reactions (ASRs) (e.g. burning, itching and pain at the treatment site), as reported by the subjects, and local skin reactions (LSRs) (e.g. erythema, erosion, scabbing and crusting), assessed by the investigator as per a rating scale defined in the protocol. Typically, the frequency of these treatment-emergent effects increases as dosing frequency increases.
In cases where the tumour had cleared after imiquimod treatment, it is important to be confident that the correct area was located and assessed. The earlier studies had used a combination of anatomical drawings, photodocumentation and a plastic template marking skin landmarks in order to find the site of the original target tumour. In this phase III study, the aim was to compare the safety and efficacy of imiquimod (Aldara; 3M Pharmaceuticals, St Paul, MN, U.S.A.) 5% cream with vehicle cream applied 7 ×/week for 6 weeks for the treatment of sBCC in subjects whose tumours were marked with a central indelible mark before treatment initiation. Marking the tumours in this way further assures the validity of the efficacy measurement.
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