Electrochemotherapy : Aspects of preclinical development and early clinical experience

To develop an optimized, reproducible system of electrochemotherapy, and to investigate its clinical application in patients with cutaneous or subcutaneous recurrences of inoperable or progressive disease recalcitrant to current anticancer treatments. Electrochemotherapy is the application of electr...

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Bibliographic Details
Published in:Annals of surgery 2007-03, Vol.245 (3), p.469-479
Main Authors: LARKIN, John O, COLLINS, Christopher G, AARONS, Simon, TANGNEY, Mark, WHELAN, Maria, O'REILY, Seamus, BREATHNACH, Oscar, SODEN, Declan M, O'SULLIVAN, Gerald C
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - administration & dosage
Biological and medical sciences
Bleomycin - administration & dosage
Breast Neoplasms - drug therapy
Carcinoma, Renal Cell - drug therapy
Carcinoma, Squamous Cell - drug therapy
Electrochemotherapy - instrumentation
Female
Finite Element Analysis
General aspects
Humans
Kidney Neoplasms - drug therapy
Medical sciences
Melanoma - drug therapy
Mice
Mice, Nude
Neoplasm Transplantation
Neoplasms, Experimental - drug therapy
Neoplasms, Experimental - immunology
Original
Transplantation, Heterologous
Tumor Cells, Cultured
Uterine Cervical Neoplasms - drug therapy
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Summary:To develop an optimized, reproducible system of electrochemotherapy, and to investigate its clinical application in patients with cutaneous or subcutaneous recurrences of inoperable or progressive disease recalcitrant to current anticancer treatments. Electrochemotherapy is the application of electric pulses to tumor tissue, rendering the cell membranes permeable to otherwise impermeant or poorly permeant anticancer drugs. This facilitates a potent local cytotoxic effect. The optimal parameters for electrical pulses and bleomycin concentration were obtained in vitro and then applied to tumors derived from 4 histologically distinct human cancer cell lines (7860, PC3, OE19, MCF-7) established in athymic nude mice. Comparison was made with tumors that received bleomycin alone, electric pulses alone, and untreated controls. The optimized electrochemotherapy was then applied to patients with cutaneous or subcutaneous tumors, of any histologic type, recurrent or metastatic and unresponsive to standard chemotherapy and/or radiotherapy regimens. Tumors were assessed at monthly intervals to determine response to the treatment. In vivo: Using the optimal parameters ascertained in vitro, all tumors treated by electrochemotherapy with bleomycin (n = 24) had significantly regressed (P < 0.001, all 4 lines) compared with control tumors (n = 72). Twelve tumors completely regressed (50%) following a single application, with 12 partial regressions (50%). Clinical: In 30 patients (111 tumors), none of the treated tumors progressed. Sixty percent of tumors (66 of 111) showed complete regression, 22% (24 of 111) partial response, and 18% (21 of 111) no change. Electrochemotherapy was more effective in smaller tumors (
ISSN:0003-4932
1528-1140
DOI:10.1097/01.sla.0000250419.36053.33