Efficacy Of Electrochemotherapy Research Articles

Successful treatment of equine sarcoids with cisplatin electrochemotherapy: A retrospective study of 48 cases

Sarcoids are the commonest form of equine skin tumour. Several therapeutic measures have been described but none is considered to be universally effective. Electrochemotherapy (ECT) is a new anticancer therapy that utilises electrical field pulses to induce increased cell membrane permeability to antitumour hydrophilic drugs, such as cisplatin. The increased intracellular concentration of the drugs has a significant therapeutic benefit. The procedure has not been previously reported in a large number of horses. To validate ECT as a novel alternative treatment for equine sarcoids. A retrospective study evaluating the efficacy of cisplatin ECT in the treatment of equine sarcoids was performed. Electrochemotherapy treatments were applied under general anaesthesia at 2 week intervals with or without prior excision or debulking. Electric pulses were directly applied to the lesions following intra-tumoural injections of an aqueous solution of cisplatin. One-hundred-and-ninety-four sarcoids on 34 horses, 2 ponies, 11 donkeys and one mule were treated with ECT. The 4 year nonrecurrence rate was 97.9% for animals (47/48) and 99.5% (193/194) for tumours. When ECT was used as a single treatment, a significant influence of tumour size (ρ= 0.55) on the number of treatments required for cure was shown. When prior surgery was performed, there was a significant influence (P<0.001) of the excision quality (complete or incomplete) and the healing mode (closed or open wound) on the number of treatments. The most common adverse effect was a slight oedematous reaction for lesions located on thin skin regions. Results demonstrate that ECT, with or without concurrent tumour debulking, is an effective alternative for treatment of equine sarcoids.

Microdevice for Analyzing the Effect of Electrochemotherapy on Cancer Cells

A microfabricated cell-based testing device for electrochemotherapy (ECT) has been developed; it mimics a clinical electroporator with a circular needle array and maintains a similar electric field strength distribution. Until now, the performance between electroporators having two- and six-needle circular array electrodes, which are the general needle-type clinical electroporators for ECT, has not been evaluated systemically, although many studies have investigated the efficacy of ECT on cancer cells. In this study, the cell-based performance on the newly developed ECT testing device was analyzed in two- and six-electrode modes using propidium iodide and bleomycin, and the electroporation characteristics were characterized. With on-chip fluorescence-based assays, the proposed device offers time- and cost-effective experimental procedures compared with conventional assays, and the results can reflect the electric characteristics of clinical electroporators.

Electrochemotherapy a novel approach to the treatment of metastatic nodules on the skin and subcutaneous tissues

Electrochemotherapy (ECT) is a new treatment for metastatic nodules of solid tumors on the skin or subcutaneous tissue. ECT is a combination of a physical effect, cell membrane poration, and cytotoxic drug administration. Cell membrane poration is achieved by applying short intense electric filed pulses. Pore formation on the cell membrane allows low permeant drugs like bleomycin or cisplatin to enter the cell and thus locally increase their toxicity: up to 10.000 times for bleomycin and 80 times for cisplatin. ECT has been investigated in a multicenter study European Standard Operating Procedures for Electrochemotherapy (ESOPE) that demonstrates how by ECT over 80% of the cutaneous or subcutaneous metastatic nodules can be healed, thus confirming the results of previous studies. ECT efficacy is independent of tumor histology. The experience gathered in the ESOPE study allowed to prepare standard operating procedures that are key to the dissemination of the technology. ECT is safe effective, the treatment is completed in one session usually on an out-patient basis with minimum side-effects. ECT is cost-effective and, although palliative, it ameliorates patients' quality of life. ECT is the treatment of choice for tumors refractory to conventional treatment, can be used in form of cytoreductive therapy before conventional treatment for organ sparing and functions saving, finally can be adopted to treat hemorrhagic or painful nodules, it can be applied in previously irradiated areas.

Intraoperative versus postoperative electrochemotherapy in high grade soft tissue sarcomas: a preliminary study in a spontaneous feline model

Feline soft tissue sarcomas are spontaneous, rapidly growing, and aggressive neoplasms that mimic their human counterpart. The purpose of this study was to evaluate the feasibility and efficacy of electrochemotherapy (ECT) in an adjuvant fashion for the treatment of feline sarcomas, and the possibility of repeated treatments in the case of recurrence. Cats with fibrosarcoma (FSA) were assigned to receive surgery or surgery plus ECT. Feline patients recruited in the ECT study were enrolled in a microscopic arm (39 patients) or a macroscopic arm (19 patients) on the basis of their tumor status (absence or presence of gross disease). Patients received local injection of bleomycin followed by bursts of eight biphasic pulses at a voltage of 1,300 V/cm for postoperative and of 800 V/cm for intraoperative treatments. The median time to recurrence was 4 months for cats treated with surgery alone, 19 months for the postoperative cohort, and 12 months for the intraoperative group. Moreover, ten patients with recurring neoplasms were retreated and experienced responses lasting 6 to 28+ months. Side effects were minimal. Of interest, the metastatic rate (1.7%) in our patients was negligible: only one cat had distant spread. The results suggest that ECT is a well tolerated and potentially useful addition to surgery in controlling high-grade sarcomas. On the basis of these results, additional evaluations are warranted in pets and in humans.

Effectiveness of tumor electrochemotherapy as a function of electric pulse strength and duration

The aim of this study was to evaluate the effectiveness of electrochemotherapy (ECT) as a function of various combinations of pulse strength and duration. C57Bl mice bearing LLC tumors were injected i.p. with bleomycin (BLM) at doses 5 mg/kg in 0.2 ml of physiological saline. Thirty minutes later, tumors were positioned between plate electrodes and were pulsed with eight-square wave electric pulses with an individual pulse strength of 900, 1100, 1300 or 1500 V/cm and duration of 0.1, 0.25, 0.5 or 1 ms. Effectiveness of ECT was estimated by measuring inhibition of tumor growth and by estimating extent of necrosis in histological slices of the treated tumors. At pulse strength of 900 V/cm and duration of 0.1 ms, electrochemotherapy was ineffective. Noticeable inhibition of tumor growth (threshold of ECT) was obtained when pulse duration at this field strength was increased up to 0.25 ms. Further increase of pulse strength and/or duration resulted in progressive enhancement of antitumor effects. Using tumor doubling time (DT) as a criteria, we showed that the same efficacy of ECT could be achieved using various pairs of values for pulse strength and duration. Largest antitumor efficacy of ECT was obtained at pulse strength of 1500 V/cm and duration of 1 ms. These pulse conditions applied alone neither significantly suppressed tumor growth nor induced noticeable side effects of the surrounding tissues. The results of this study thus suggest that the effectiveness of electrochemotherapy can be enhanced (in comparison to widely accepted conditions of electrochemotherapy—8 pulses of 1300 V/cm, 0.1 ms) if 1500-V/cm, 1-ms electric pulses are used. Our study also implicates that other pulse conditions could be found for this enhanced ECT.

In-vitro and in-vivo studies of the efficacy of electrochemotherapy for renal cell carcinoma

Background. We aimed to assess a new approach to cancer therapy, using pulsed electric fields to facilitate the delivery of chemotherapeutic drugs. Methods. We investigated the cytotoxic effects on renal cell carcinoma of combinations of some well established anticancer drugs with electrical impulses, both in vitro and in vivo. The in-vivo study was done in nude mice bearing transplanted tumors. Results. In vitro, the treatments resulted in greater cytotoxic effects than either bleomycin (BLM) or high-voltage electrical impulses, alone. In renal cell carcinoma-bearing mice, the application of high-voltage electrical impulses to tumors, after the injection of BLM, resulted in disappearance of the tumors within 4 days. Such complete regression was achieved at a single BLM dose of 0.1 × lethal dose (LD)50, when combined with electrical in pulses. The tumors regrew after day 10, but at a much slower rate than at other concentrations of BLM. Other drugs used; cisplatin, 5-fluorouracil, mitomycin-C, and vinblastin, showed no retardation of tumor growth when compared with the results in “no-pulse” controls. The complete regression of tumors was associated with increased DNA cleavage and cell death. Conclusion. The concomitant use of high-voltage electrical impulses with BLM has the potential to increase the efficacy of BLM treatment of renal cancer, as reflected in substantial reduction in tumor growth.

Electrochemotherapy on liver tumours in rabbits.

Electrochemotherapy (ECT) is a new therapeutic approach combining the effects of a low-permeant cytotoxic drug, bleomycin (BLM), administered i.v. and cell-permeabilizing electric pulses (EPs) locally delivered to tumours. The transient permeabilization of the cell membrane by the EPs allows free access of BLM to its intracellular targets, largely enhancing BLM's cytotoxic effects. ECT efficacy has been proved so far on transplanted subcutaneous murine tumours and on subcutaneous metastases in humans. Here, we present the first study of the effects of ECT on tumours transplanted to livers in rabbits. We used a recently developed EP applicator consisting of an array of parallel and equidistant needles to be inserted in tissues. Effects of EPs alone or of ECT were assessed by histological analysis, tumour growth rates and survival of the treated animals. A transient blood hypoperfusion was seen in the electropulsed areas, with or without BLM, related to EP-dependent vasoconstriction but this had no major effects on cell survival. Long-term effects depended on the presence of BLM at the time of EP delivery. Almost complete tumour necrosis was observed after ECT, resulting from both BLM direct cytotoxic effects on electropermeabilized tumour cells and indirect effects on the tumour vessels. A large reduction in tumour growth rate and significantly longer survival times were scored in comparison with control rabbits. Moreover, ECT of liver tumours was well tolerated and devoid of systemic side-effects. When ECT was associated with a local interleukin 2-based immunotherapy, increased local anti-tumour effectiveness as well as a large decrease in the number of metastases were observed. Thus, ECT could become a novel treatment modality for liver tumours and other solid internal malignancies.