A New Brain Tumor Therapy Combining Bleomycin with in Vivo Electropermeabilization

Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy

“…However, electric pulses delivered alone did not elicit an anti-tumour response. Anti-tumour effects were observed in many different animal models Salford et al, 1993;Mir, 1994;Ser'sa et al, 1994;1995;Yamaguchi et al, 1994;Cemazar et al, 1995;Heller et al, 1995). Anti-tumour treatment with this combined therapy can be used in tumour systems in which bleomycin alone was not typically used .…”

First clinical trial of cat soft-tissue sarcomas treatment by electrochemotherapy

“…For the 12 cats of the treated group, BLM at a dose of 0.5 mg kg-' was injected intravenously in a bolus that lasted 30 s. This dose, similar on a body weight basis to that used in other preclinical and clinical trials Salford et al, 1993;Heller et al, 1994;Sersa et al, 1994;Yamaguchi et al, 1994), is totally ineffective in the absence of the potentializing EP. The nodules of the first cats and the thin nodules of other cats were treated using the procedure previously tested in other animal species as well as in humans Mir et al, 1991Mir et al, , 1992, i.e.…”

“…This geometry defines 12 pairs of closest electrodes (needles), all separated by the same distance, 6 mm, and thus the tumour is divided into 12 volume units treated (Belehradek et al, 1994) showed that 500-600 V cm-1 was the minimal electric field intensity necessary to obtain cell permeabilization with electrodes directly in contact with tissues. Moreover, 800 V cm-' was the electric field intensity previously delivered using only two needles for the treatment of gliomas transplanted intracranially in rats (Salford et al, 1993).…”

“…Electrochemotherapy is effective in eradicating subcutaneously transplanted small tumours Serka et al, 1994;Heller et al, 1994;Yamaguchi et al, 1994). Good antitumour responses were also obtained in a murine spontaneous tumour model and with internally transplanted tumours (Salford et al, 1993). In the absence of BLM, the applied EPs did not perturb tumour growth; conversely, in the absence of EPs, the doses of BLM injected did not reduce tumour growth whichever experimental or clinical model was tested in the work cited above.…”

“…This trial using cats was designed as an actual phase I clinical trial of a new therapeutic procedure: we recruited only cats for which there was no proposed treatment. As we had already shown in mice, rats, rabbits and humans that neither BLM alone, given at 0.5-1.0 mg kg-' (10 or 15 mg m-2 in humans produces doses of the same size) in a single intravenous bolus, nor the permeabilizing EP alone, delivered either by surface electrodes or by needle electrodes, was able to perturb tumour growth Belehradek et al, 1993;Salford et al, 1993;Sersa et al, 1994;Ramirez et al, submitted), the trial was focused on the comparison of completely treated cats with untreated ones. The results reported here open the way for initiating human clinical trials of electrochemotherapy using the new device for intratumoral EP delivery.…”