Electrically enhanced drug delivery for the treatment of soft tissue sarcoma

BACKGROUND. Pulsed electric fields have been shown to increase the effectiv eness of antineoplastic agents by temporarily increasing the permeability o f cell membranes. This type of drug delivery is called electrochemotherapy, and it has been successful in the treatment of patients with cutaneous mal ignancies in clinical trials. This study focused on determining the applica bility of electrochemotherapy to the treatment of soft tissue sarcoma, usin g an animal model bearing human sarcomas. The antitumor effects of single a nd multiple electrochemotherapy treatments were investigated using small (2 50 mm(3)) and large (4000 mm(3)) tumors. METHODS. Established tumors were injected with bleomycin, then electric pul ses were administered to the tumor site. Animals were followed based on per iodic tumor Volume determinations, which were used to categorize treatment of each tumor as a complete response, a partial response, stable disease, o r progressive disease. Histologic analysis was used to confirm response dat a. RESULTS. Animals were randomly assigned to one of four different treatment groups. These groups received no treatment, drug only, electric pulses only , or drug combined with electric pulses. A single electrochemotherapy treat ment protocol for small tumors resulted in a 100% complete response rate an d a 41.7% cure rate. Multiple treatments of small and large tumors resulted in complete response rates of 83.3% and 100%, respectively. These response s were identical to the cure rates. In contrast, tumors in the groups that received no treatment, electric pulses only, and drug only progressed for b oth single treatment and multiple treatment scenarios, regardless of tumor size. CONCLUSIONS. In this study, a single electrochemotherapy treatment had a st rong cytoreductive effect on small tumors that lasted approximately 35 days , until recurrences began. Multiple treatment of small and large tumors res ulted in high complete response rates that lasted at least 100 days after t reatment. This indicates the feasibility of electrochemotherapy as a modali ty of limb-preserving treatment for patients with sarcoma of the extremitie s. (C) 1999 American Cancer Society.