Electrically enhanced drug delivery for the treatment of soft tissue sarcoma.

Abstract

Pulsed electric fields have been shown to increase the effectiveness of antineoplastic agents by temporarily increasing the permeability of cell membranes. This type of drug delivery is called electrochemotherapy, and it has been successful in the treatment of patients with cutaneous malignancies in clinical trials. This study focused on determining the applicability of electrochemotherapy to the treatment of soft tissue sarcoma, using an animal model bearing human sarcomas. The antitumor effects of single and multiple electrochemotherapy treatments were investigated using small (250 mm3) and large (4000 mm3) tumors. Established tumors were injected with bleomycin, then electric pulses were administered to the tumor site. Animals were followed based on periodic tumor volume determinations, which were used to categorize treatment of each tumor as a complete response, a partial response, stable disease, or progressive disease. Histologic analysis was used to confirm response data. 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 treatment protocol for small tumors resulted in a 100% complete response rate and a 41.7% cure rate. Multiple treatments of small and large tumors resulted in complete response rates of 83.3% and 100%, respectively. These responses were identical to the cure rates. In contrast, tumors in the groups that received no treatment, electric pulses only, and drug only progressed for both single treatment and multiple treatment scenarios, regardless of tumor size. In this study, a single electrochemotherapy treatment had a strong cytoreductive effect on small tumors that lasted approximately 35 days, until recurrences began. Multiple treatment of small and large tumors resulted in high complete response rates that lasted at least 100 days after treatment. This indicates the feasibility of electrochemotherapy as a modality of limb-preserving treatment for patients with sarcoma of the extremities.