Randomized controlled study of electrochemotherapy in the local treatment of skin metastases of melanoma

Background. Electrochemotherapy (ECT) combines intralesional injections of bleomycin with electroporation (EP), which permeabilizes tumor cells and thus increases the bleomycin efficacy at the tumor site. Objective: To assess whether EP therapy improves the local control of skin metastases of melanoma by intralesional bleomycin. The secondary objective was to evaluate tolerance of the treatments. Patients: Patients with at least two measurable skin metastases of melanoma that were previously untreated, either in stage III with in-transit melanoma skin metastases or stage IV with no efficacy of systemic chemotherapy on these metastases. Design: A prospective internally controlled study with randomization of melanoma skin metastases in each individual to intralesional injections of bleomycin alone or to intralesional injections of bleomycin with EP. The primary end point was the rate of complete local response per treated melanoma skin metastasis at week 12, and the secondary end point was tolerance. Results: Fifty-four melanoma skin metastases were treated in 12 patients (8 stage IV patients under chemotherapy and 4 stage III patients free of other treatment). A local complete response was obtained in 36% (11 of 30) of melanoma skin metastases treated with bleomycin + EP and only in 8% (2 of 24) of melanoma skin metastases treated with bleomycin alone (p = .016). In the per protocol population, complete response was obtained in 74% (17 of 23) and 13% (2 of 15) of the lesions treated, respectively (p = .017). All patients (12 of 12) reported discomfort during the EP procedure, including local pain for 9 patients (75%) at the treatment site and muscle spasm with myoclonia in 3 cases (25%). No clinical or biologic systemic toxicity was noticed. Conclusions: EP increases the effect of intralesional bleomycin and improves the rate of local control in melanoma skin metastases without inducing a more systemic effect. This local treatment could be useful in a palliative strategy in patients with melanoma skin metastases.