title: Definition of novel electrochemotherapy parameters and validation of their in vitro and in vivo effectiveness.
abstract: Electrochemotherapy (ECT) is a cancer therapy that conjugates the administration of a chemotherapy agent to the delivery of permeabilizing pulses released singularly or as bursts. This approach results in higher number of anticancer molecules delivered to their biological targets, but is also associated to undesirable side effects such as pain and muscular contractions. A new electroporator delivering train of eight biphasic pulses at the voltage of 1,300 V/cm lasting 50 + 50 µsec each, with a frequency of 1 Hz, and with 10-µsec interpulse intervals (total treatment time: 870 µsec/cm(2) of treated area) was tested in vitro on the human lung cancer cell line A549 and in vivo, both in mice xenografts and privately owned rabbits with spontaneous tumors. The tumor cell line was treated with electroporation using the new parameters, that showed improved drug efficacy in causing cell death. Mice with chemoresistant xenografts were treated as well with either the new parameters and with a previous protocol, confirming the higher tolerability and efficacy of the novel parameters. Finally, a cohort of six pet rabbits with advanced skin neoplasms were enrolled in a compassionate trial using the new parameters in adjuvant fashion. In terms of efficacy, none of the rabbits experienced tumor recurrence, showing minimal discomfort during the ECT sessions. The data described, demonstrate that the new permeabilizing protocol adopting biphasic electric pulses displays a significant higher efficacy compared to previous ECT treatments and substantial reduction of the associated morbidity.
authors.affiliation: Biopulse S.r.l., Naples, Italy.
authors.forename: Enrico P
authors.initials: EP
authors.lastname: Spugnini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Melillo
authors.forename: Lucio
authors.initials: L
authors.lastname: Quagliuolo
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Boccellino
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Paola
authors.initials: P
authors.lastname: Pasquali
authors.forename: Alfonso
authors.initials: A
authors.lastname: Baldi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage*; D019008:Drug Resistance, Neoplasm; D053672:Electrochemotherapy / Q000009:adverse effects / Q000379:methods / Q000662:veterinary*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D011817:Rabbits; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin