Electrochemotherapy Treatment of Locally Advanced and Metastatic Soft Tissue Sarcomas: Results of a Non‐Comparative Phase II Study

Abstract

Our aim was to evaluate the activity, toxicity, and feasibility of electrochemotherapy (ECT) in patients with soft-tissue sarcomas (STS). A two-stage phase II trial was conducted between October 2006 and March 2012. Patients (N = 34) with locally advanced or metastatic STS, unsuitable for standard oncological treatments and with maximum 3-cm deep tumors, received an intravenous bolus of bleomycin (15,000 IU/m(2)), followed by tumor electroporation according to the European Standard Operating Procedures of ECT. Outcome measures included local response according to response evaluation criteria in solid tumors (RECIST), toxicity and tumor control. Feasibility measures included the accuracy of electrode placement and the intensity of electric current flowing in tumor tissue. Median tumor size was 4.0 cm (range 2-12). Objective response, assessed on 71 target lesions, was 92.2 % (complete 32.3, 95 % CI 28-64). A total of 15 patients received up to four cycles due to incomplete response, but re-treatment did not significantly improve outcome (p = 0.205). After a median follow-up of 19.3 months, 2-year local control rate was 72.5 %. Median time to local failure (N = 11 patients) was 5.1 months. Tumor response (p = 0.041) and control (p = 0.047) correlated with histological grading. Relevant toxicity consisted of G3 skin ulceration and soft tissue necrosis (35 and 23 % of patients, respectively), although this was manageable on an outpatient basis. The accuracy of electrode placement was 47.1 %, and the adequacy of electroporative current 85.3 %. ECT may represent an active and safe treatment to achieve local control in advanced STS patients with symptomatic disease. Future research challenges include the improvement of electrode placement and voltage delivery together with the containment of soft tissue toxicity.