Improvement of combined modality therapy with cisplatin and radiation using electroporation of tumors

Purpose: To evaluate whether a local drug delivery method, i.e., electroporation of tumors, increases the radiosensitizing effect of cisplatin. Methods and Materials: Subcutaneous Ehrlich-Lettre ascites (EAT) tumors in CBA mice were treated either by cisplatin, electric pulses, or ionizing radiation. In electrochemotherapy protocol, electric pulses were given to the tumor 3 min after intravenous injection of cisplatin. The interval between electrochemotherapy and irradiation was 20 min. Treatment effectiveness was evaluated by tumor growth delay and local tumor curability. Results: Electrochemotherapy of EAT tumors proved to be effective treatment, resulting in 12% tumor cures, whereas treatment with cisplatin or electric pulses alone did not yield any tumor cures. As expected, injection of cisplatin 20 min prior to irradiation, increased radioresponse of tumors from 27% to 73% tumor cures. Electroporation of tumors also increased radiation response of tumors to 54% tumor cures. Electrochemotherapy given prior to irradiation increased radioresponsiveness of tumors, resulting in 92% tumor cures. Conclusions: This study shows that delivery of cisplatin into the cells by electroporation of tumors increases the radiosensitizing effect of cisplatin. However, some effect may also be ascribed to application of electric pulses to the tumors that in our study also predisposed tumor cells to radiation damage