Electrochemotherapy, a new antitumor treatment. First clinical phase I-II trial

Abstract

Background. Electrochemotherapy is a new antitumor treatment consisting of electrical pulses administered to the tumor several minutes after intravenous injection of bleomycin. In mice, important antitumor effects were observed on subcutaneously transplanted tumors and on spontaneously occurring mammary carcinomas. Cures were obtained after one single treatment combining bleomycin and electric pulses. In humans, permeation nodules seemed an adequate oncologic situation to assay this new procedure. The authors report the first Phase I‐II trial of electrochemotherapy. Methods. Eight patients with 40 permeation nodules of head and neck squamous cell carcinomas were treated with 10 mg/m2 bleomycin intravenous bolus, followed by four or eight short (100 μseconds) and intense (1300 V/cm) pulses administered through two external electrodes located on each side of the treated nodule. Results. An instantaneous painless contraction of the underlying muscles was regularly observed. Neither local nor general side effects were observed, and electrochemotherapy was well tolerated. In addition, a clear local antitumor efficacy was found: 23 (57%) nodules were in clinical complete response within a few days. Conclusion. The absence of toxicity, the good tolerance by the patients, and the net antitumor effects observed are encouraging for additional electrochemotherapy developments in clinical oncology.

Electromobility of plasmid DNA in tumor tissues during electric field-mediated gene delivery

“…[2][3][4][5] Clinical trials of electric field-mediated drug delivery have been conducted to treat tumors. 6,7 These studies demonstrate that it is feasible and safe to use electric fields to facilitate drug and gene delivery.…”

DNA electrotransfer: its principles and an updated review of its therapeutic applications

“…22 Moreover, because of the antitumour efficacy of this approach, clinical trials were rapidly performed. 23,24 This approach was termed electrochemotherapy, and the pulse conditions, used in almost all the published clinical trials, [25][26][27] were eight identical square wave pulses of 100 ms and 1300 V/cm at a repetition frequency of 1 Hz using external electrodes (transcutaneous pulses). These trials demonstrated that it is possible to deliver in vivo electric pulses to animals and patients and they greatly facilitated the development of the in vivo DNA electrotransfer.…”

Effects of Dimethyl Sulfoxide on Lipid Membrane Electroporation

“…2 The latter has resulted in a new tool to battle cancer, electrochemotherapy, which is based on the application of pulses that induce the electroformation of reversible pores in the cell membrane, thereby allowing the delivery of non-permeant drugs inside tumor cells. 2,3 Membrane pores can also be chemically induced by the use of particular membrane-fluidizing compounds such us dimethyl sulfoxide (DMSO, (CH 3 ) 2 SO), a small amphiphilic molecule that has been shown to enhance cell permeability through the formation of water pores. 4,5 Recently, molecular dynamics (MD) simulations have been used to elucidate the molecular mechanisms leading to pore formation in simple lipid bilayers by both the application of an external electric field [6][7][8][9][10] and the effects of DMSO.…”