Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy.

L M Mir ,M Belehradek,Mj Jaroszeski,Ds Reintgen,Z Rudolf,P Coninx,Damijan Miklavčič ,J.m Bachaud ,Gregor Serša ,L Frank Glass ,Borut Štabuc ,R Alton Gilbert ,Marie‐Pierre Rols ,Jean Belehradek ,C Domenge ,Stéphane Orlowski ,Maja Čemažar ,Ronald C Deconti ,J Teissié ,Richard Heller

doi:10.1038/bjc.1998.388

Abstract

Electrochemotherapy (ECT) enhances the effectiveness of chemotherapeutic agents by administering the drug in combination with short intense electric pulses. ECT is effective because electric pulses permeabilize tumour cell membranes and allow non-permeant drugs, such as bleomycin, to enter the cells. The aim of this study was to demonstrate the anti-tumour effectiveness of ECT with bleomycin on cutaneous and subcutaneous tumours. This article summarizes results obtained in independent clinical trials performed by five cancer centres. A total of 291 cutaneous or subcutaneous tumours of basal cell carcinoma (32), malignant melanoma (142), adenocarcinoma (30) and head and neck squamous cell carcinoma (87) were treated in 50 patients. Short and intense electric pulses were applied to tumours percutaneously after intravenous or intratumour administration of bleomycin. The tumours were measured and the response to the treatment evaluated 30 days after the treatment. Objective responses were obtained in 233 (85.3%) of the 273 evaluable tumours that were treated with ECT. Clinical complete responses were achieved in 154 (56.4%) tumours, and partial responses were observed in 79 (28.9%) tumours. The application of electric pulses to the patients was safe and well tolerated. An instantaneous contraction of the underlying muscles was noticed. Minimal adverse side-effects were observed. ECT was shown to be an effective local treatment. ECT was effective regardless of the histological type of the tumour. Therefore, ECT offers an approach to the treatment of cutaneous and subcutaneous tumours in patients with minimal adverse side-effects and with a high response rate.

Highlights

Chemotherapy is a widely used treatment for a broad range of cancers
For example, partial response rates range from 20% to 45%, with complete responses of less than 5% (Buzaid and Murren, 1992; Coates, 1992; Nathanson and Jilani, 1993; Yeung, 1994)
A total of 50 patients were treated at five different cancer centres in 66 ECT sessions

Summary

Introduction

Chemotherapy is a widely used treatment for a broad range of cancers. The application of short and intense electric pulses can reversibly permeabilize membranes of all living cells, including mammalian, bacterial, yeast and plant cells (Mir et al, 1988; Neumann et al, 1989; Rols and Teissie, 1990; Orlowski and Mir, 1993). These electric pulses have been used in vitro to introduce drugs, foreign DNA and other exogenous molecules into cells (Orlowski and Mir, 1993)

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