Combined treatment of electrochemotherapy with irradiation

Abstract

Radiotherapy is the use of ionizing radiation in the treatment of malignant tumors. It is one of the main treatment modalities for many forms of cancer, with more than half of all cancer patients receiving radiation therapy at some point in their treatment. Despite the technical progress in targeting ability of radiotherapy, poor therapeutic window remains a problem; therefore in clinical practice radiotherapy is commonly combined with chemotherapy. By using electrochemotherapy, the uptake of the non or poorly permeable chemotherapeutic drugs, bleomycin and cisplatin, into the tumors can be increased and thus also their radiosensitizing effect. In combined treatment of electrochemotherapy preceding irradiation, an increased radio-response was demonstrated with an enhancement factor of up to 4.6, regardless of using radiomimetic (bleomycin) or radiosensitizing (cisplatin) drug. The improved antitumor effectiveness is mainly enabled by increased drug accumulation in the tumors. Radiosensitization was demonstrated in vitro and in vivo in variable tumor models irradiated in a single dose and a fractionated regime. Low and acceptable radiation damage of normal tissue in the irradiation field was observed. All the data provided a starting point for translation of combined electrochemotherapy and tumor irradiation into the clinic, which has already begun.