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.