Electrochemotherapy for the treatment of melanoma skin metastases in the era of new drugs

Abstract

SummaryThe incidence of melanoma has been increasing for more than 40 years and in the clinical course of this neoplasia cutaneous metastases are not unusual. Electrochemotherapy (ECT) is an already well recognised therapeutic tool for the local treatment of cutaneous and subcutaneous metastases of melanoma showing sustained anti-tumour activity and favourable toxicity profile. Treatment involves the local or intravenous administration of chemo therapeutic drugs followed by delivery of electrical pulses to the tumour. Recent advances in systemic therapies have dramatically modified melanoma therapeutic approach on stage III and IV with increased survival rates. However, the cutaneous metastases management still represents a challenge for clinicians due to pain, bleeding, odour and psychosocial distress related to the lesions but also for the limited efficacy on the skin offered by newly available systemic strategies. ECT may be considered for local tumour control as an alternative to established local treatments but it could be also favourably associated to immune and target therapies to improve their efficacy. Recent findings suggest indeed that electrochemotherapy may exert a role in boosting anti-tumour immunity and to avoid skin metastases resistance to systemic treatments.KEY WORDS: electrochemotherapy; melanoma skin metastases; immunotherapy; target therapy. IntroductionThe incidence of melanoma has been increasing for more than 40 years in western countries, although the incidence rate for all cancer sites combined is decreasing. Since 1975, age-standardized melanoma incidence in the United States nearly tripled to 22.9 per 100,000 persons in 2012 and also in Italy in the last 10 years melanoma diagnosis are almost doubled. Talking about prognosis, the 10-year survival rate for patients with an early-stage melanoma is greater than 95% but prognosis is much more severe for patients diagnosed with advanced disease: an overall 1-year survival of 25.5% and a median survival of 6.2 months were achieved, without any significant improvement during the last 30 years (1). Melanoma accounts for about 18% of the total cases of cutaneous metastases (2) even if their management is often challenging. In fact, patients with cutaneous disease may suffer from pain, bleeding, and malodour determining a reduced quality of life. Since 2006, electrochemotherapy (ECT) has been introduced as a standardized procedure in the field of dermato-oncology as a treatment option for cutaneous and subcutaneous lesions, including melanoma. ElectrochemotherapyThe first human trial conducted on 1991 demonstrated the efficacy and safety of electrochemotherapy in the treatment of cutaneous and subcutaneous metastases from different primary tumours. Then the field has rapidly developed since the procedure has been recognized as an effective and safe local treatment for cutaneous, subcutaneous and mucosal lesions (3,4). A European project published in 2006 (ESOPE) established standardized operating procedures (5). The treatment can be administe...