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.     

Dermoscopic patterns of superficial basal cell carcinoma

Background Superficial basal cell carcinoma (BCC) presents as a scaly, pink to red–brown patch and is predominantly located on the trunk. Clinical diagnosis may not be always easy and implicates a variety of differential diagnoses; in this situation dermoscopy has been reported improving the diagnostic accuracy. This study investigated dermoscopic patterns of superficial BCC focalizing the most specific and frequent structures in order to improve the diagnostic accuracy. Limitations Study population referred to skin lesion clinic. Methods Dermoscopic patterns of 42 superficial BCCs were analyzed and photographed. These cases represented the 8% of all BCCs excised in our Department between 2005 and 2006. Results Dermoscopic structures observed in the 42 superficial BCCs consisted of shiny white to red areas (100%), “erosions” (78.6%), short fine telangiectasias (SFTs) (66.6%), leaf‐like areas (16.6%), arborizing telangiectasias (14.3%), blue–gray globules (14.3%) and large blue–gray ovoid nests (4.7%). Conclusions Our study identifies the presence of shiny white to red areas, SFTs and “erosions” as main dermoscopic criteria of superficial BCC. Other dermoscopic features, such as leaf‐like areas, arborizing telangiectasias, blue–gray globules and large blue–gray ovoid nests, are not strongly associated with the diagnosis of superficial BCC but they are useful in the differential diagnosis from other pigmented and nonpigmented skin lesions.     

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.     

Imiquimod simultaneously induces autophagy and apoptosis in human basal cell carcinoma cells

Background Imiquimod shows antitumour activity through the stimulation of cell‐mediated immunity in vivo. Recent studies have shown that imiquimod promotes apoptosis in melanoma cells and induces autophagy in macrophage cell lines. Objectives To evaluate the imiquimod‐induced apoptosis, autophagy and their relationship in a basal cell carcinoma (BCC) cell line. Methods Cell viability was determined by XTT test. Apoptosis was evaluated by DNA content assay, annexin V/propidium iodide staining assay and terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labelling assay. Autophagy was determined by LC3 immunoblotting, EGFP‐LC3 puncta formation and quantification of acidic vesicular organelles with acridine orange staining. The temporal and spatial differences of imiquimod‐induced apoptosis and autophagy were examined by immunoblotting and simultaneously monitored by staining the EGFP‐LC3 transfected cells with caspase 3 fluorogenic substrate. We inhibited the apoptosis and autophagy by pancaspase inhibitor and siRNA for Beclin 1 or Atg5, respectively, to evaluate the interplay between imiquimod‐induced apoptosis and autophagy. Results We found that imiquimod induces autophagy and apoptosis in BCC cells in a time‐ and dose‐dependent manner. Imiquimod not only induced EGFP‐LC3 puncta formation for autophagy, but also simultaneously activated an apoptotic caspase cascade in the same cells. Both apoptosis and autophagy induced by imiquimod cooperate to cause BCC cell death. However, inhibition of imiquimod‐induced apoptosis increased the strength of autophagy, and inhibition of imiquimod‐induced autophagy further promoted cell apoptosis. Conclusions This study not only demonstrates that imiquimod can directly induce autophagy and apoptosis in BCC cells, but also shows the cooperation and coordination between these two processes to induce cell death.     

Giant superficial basal cell carcinoma of the scrotum

The majority of basal cell carcinomas (BCCs) occur on sun-exposed areas. BCCs arising on the genitalia and ones over 5 cm in size are exceedingly rare. Most of the histopathologic subtypes of giant BCC are micronodular, morpheaform and nodular, but superficial subtype is rare. We reported a very rare case of a giant, scrotal superficial BCC. Scrotal carcinomas, the discovery of which is delayed, may become large. Because giant BCC is potentially life threatening, early diagnosis and adequate treatment are essential to prevent both recurrence and metastasis.     

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.     

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.     

CD-10 immunostaining differentiates superficial basal cell carcinoma from cutaneous squamous cell carcinoma

Basal cell carcinoma and squamous cell carcinoma are common entities in clinical practice. Their distinction can be difficult clinically as well as histologically. CD10 or common acute lymphoblastic leukemia antigen (CALLA) is a metallomembrane endopeptidase expressed on a variety of normal and neoplastic cells. We sought to determine if the CD10 immunostain could have diagnostic utility in distinguishing between early superficial basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). CD10 was strongly expressed in 14 out of 14 superficial BCCs and failed to express in 2 out of 2 deeply infiltrative BCCs. CD10 was negative in the tumor cells in 13 out of 13 superficially invasive SCCs and SCC in situ. CD10 expressed weakly in the surrounding stromal cells of 2 out of 13 SCCs. These findings support the utility of CD10 as a marker for early BCC, especially when SCC cannot be excluded clinically or by conventional stains. Furthermore, these results implicate CD10 in the pathogenesis of BCC.     

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 (Aldara) in the treatment of basal cell carcinoma

Skin cancer, the most common human cancer, is now a global epidemic. The most prevalent form of nonmelanoma skin cancer is basal cell carcinoma (BCC), the incidence of which continues to increase prompting development of new treatment modalities designed to add or complement current therapies. Although destructive modalities continue to be an important treatment options for BCC, nondestructive measures are a welcome addition to our therapeutic choices. Imiquimod, a topical immune response modifier, belongs to the family of immunostimulators. It enhances both the innate and acquired immune response, and has successfully treated both superficial and nodular basal cell carcinomas through the localized activation of elaborate immune response. Imiquimod can either be used alone or in combination with other treatment modalities. The most common adverse effects of topical use of imiquimod are localized to the site of application and easily managed.     

浅表型合并色素型基底细胞癌一例

患者男,51岁。因左侧腰部红斑10余年、其右下方黑色圆形斑5年,于2013年1月16日来我科就诊。患者10年前无明显诱因左侧腰部出现一甲盖大小红斑,自觉瘙痒;红斑缓慢向周围匍行性扩展,边缘隆起,有结痂。曾在当地医院及诊所按湿疹治疗多次,效果不佳,仍缓慢扩展。5年前其右下方发现一绿豆大小黑褐色斑,略有瘙痒,逐渐扩大呈圆形,边缘部分颜色较深,未特殊治疗……     

Photodynamic therapy for superficial basal cell carcinoma and Bowen's disease

Photodynamic therapy (PDT) is an effective treatment for superficial basal cell carcinoma (BCCs) and Bowen's disease. Several studies have reported complete response rates of 80-95% and an excellent cosmetic outcome. Bowen's disease and superficial basal cell carcinomas characteristically affect older patients who may also have associated difficulties with mobility. Using a portable PDT light source we were able to deliver PDT in a community setting with the aim of providing a more convenient service for patients. This randomised study confirmed that community delivered PDT is a viable treatment option and can be administered safely in the community by a trained dermatology nurse. The results from patient questionnaires suggest that community delivered PDT is more convenient to the patient, and also cost effective.     

Imiquimod induced regression of clinically diagnosed superficial basal cell carcinoma is associated with early infiltration by CD4 T cells and dendritic cells

Imiquimod is presumed to clear basal cell carcinoma (BCC) through apoptosis mediated by cytokines and lymphocytes, with erosion often observed correlating with complete clearance. The objective was to determine the cellular immune response early in the course of treatment in order to examine whether cell mediated immunity could be responsible for imiquimod mediated regression of BCC. Sixteen adults with clinically diagnosed BCC were openly assigned to 5 days per week of drug (1, 2 or 4 weeks) or placebo (2 weeks) in groups of four. No baseline biopsy was performed. Post-treatment excision specimens were examined by routine and immunohistochemical staining. Treatment was associated with the early appearance of CD4 cells, activated dendritic cells and macrophages, with later infiltration by CD8 T cells. Dendritic cells continually increased with time, while macrophages reached a maximum at 1 week and then declined slightly. There were comparatively few neutrophils or gammadelta T cells. Early infiltrates were most prominent in the tumour and upper dermis. The results are consistent with a cell mediated immune response being responsible for the clearance of the BCC. Several immune-mediated tumour destruction mechanisms are likely to be involved.     

Possibility of treating basal cell carcinomas of nevoid basal cell carcinoma syndrome with superficial x-ray therapy

BACKGROUND: The nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin-Goltz syndrome, is a rare dermatological disease inherited according to an autosomal dominant pattern. From the dermatological point of view, the most evident characteristic of the syndrome is the early onset of multiple basal cell carcinomas (BCCs). An ideal treatment of BCCs of the NBCCS does not exist. OBJECTIVE: To evaluate if in particular cases (e.g. poor general health conditions, previous multiple surgical excisions) radiotherapy may be useful, under the condition that it does not promote the onset of new BCCs and that the healing of irradiated lesions is normal. METHODS: A study on 3 patients with 17 BCCs treated with superficial radiotherapy is here reported. RESULTS: Complete remission without carcinogenic effects was reached in all treated lesions, with a mean follow-up of 30.35 months. CONCLUSION: In our opinion, such results suggest the possibility of a cautious application of superficial radiotherapy in selected cases of NBCCS.