Topical imiquimod eradicates skin metastases of malignant melanoma but fails to prevent rapid lymphogenous metastatic spread

Sir, Imiquimod [1‐(2‐methylpropyl)‐1H‐imidazo[4,5c]quinolin‐4‐amine] is a new immunomodulating agent that has been shown to possess both antiviral and antitumoral activity.1, 2 These effects are at least partially based on its role as an inducer of cytokines such as interferon‐α, tumour necrosis factor‐α, interleukin (IL)‐6 and IL‐8.3 Imiquimod has been described as an efficient topical agent in the treatment of virally induced genital and anal warts.4 Recent observations suggest imiquimod to be a new and promising agent for the topical treatment of different types of skin cancers such as basal cell carcinoma,5 squamous cell carcinoma6 and even melanoma.7, 8 The exact mechanisms of action in vivo and particularly, the range of its systemic effects after topical application, are still unclear. We report an 81‐year‐old man with melanoma, whose skin satellite metastases were successfully treated with topical imiquimod, but who was nevertheless subsequently diagnosed as having rapidly growing metastatic spread in the regional lymph node area despite ongoing therapy. The patient was first diagnosed as having malignant melanoma of the upper right arm in June 2000. Six months after complete resection of the primary lesion, he developed multiple satellite metastases surrounding the primary excision site (Fig. 1a). As he refused further surgery, topical treatment with imiquimod was initiated. Imiquimod 12·5 mg (Aldara® cream; 3M Medica, Borken, Germany) was applied daily under occlusion (OpSite transparent film; Smith & Nephew, Hull, U.K.) to the visible metastatic area of 6 cm diameter as well as to a 2‐cm margin of surrounding skin. During 12 weeks of treatment, the patient was monitored at weekly intervals on an out‐patient basis; tests included haemograms and blood chemistry. In addition, ultrasound imaging of the regional lymph nodes was performed at 4‐week intervals. Two weeks after onset of therapy, the metastatic skin area showed intense erythema, induration and small erosive patches (Fig. 1b). After 4 weeks of treatment, the erythematous area enlarged to cover the entire area undergoing topical application of imiquimod (Fig. 1c). Furthermore, the erosive patches increased in size while visible tumour nodes decreased. Thereafter, the treatment schedule was changed from daily to alternate daily application of topical imiquimod. After a total of 6 weeks of treatment the clinical signs of inflammation decreased (Fig. 1d). Ten weeks after onset of therapy the tumour residues appeared clinically undetectable, with only moderate signs of inflammation visible at the treatment site (Fig. 1e).