Evaluation of Cisplatin as an Electrochemotherapy Agent for the Treatment of Incompletely Excised Mast Cell Tumors in Dogs

Abstract

Background: Electrochemotherapy (ECT) couples the administration of anticancer drugs with the delivery of electric pulses that increase the drug uptake through the cell membranes, resulting in an improved efficacy.Hypothesis: To evaluate the tolerability and efficacy of cisplatin (CDDP) as an ECT agent to prevent recurrence of incompletely resected mast cell tumors (MCTs).Animals: Thirty-seven dogs. Methods: Prospective study recruiting dogs with incompletely excised MCTs as confirmed by surgeon and pathology reports. After debulking, the tumor bed and margins were infiltrated with CDDP, and then exposed to trains of biphasic electrical pulses under sedation. Five minutes after the injection of the chemotherapy agent, sequences of 8 biphasic pulses lasting 50 1 50 ms each, were delivered in bursts of 1,300 V/cm for sclerosed and of 800 V/cm for exposed lesions, with caliper or needle array electrodes, respectively. A second session was performed 1 or 2 weeks later based on clinical considerations.Results: The treatment was well tolerated with minimal adverse effects. Twenty-nine dogs had no evidence of recurrence over the 6-year study period, 6 had tumor recurrence, 1 died of multiple cutaneous MCTs, and 1 died of unrelated causes. The estimated median time to recurrence was 1,200 days. Recurrence was not observed among the long-term (41 year) treated dogs.Conclusions and Clinical Importance: ECT with CDDP appears effective in the treatment of incompletely resected MCT in dogs and could be a useful addition to the current options based on its low cost, limited toxicity, and ease of administration.

Advances in Therapeutic Electroporation to Mitigate Muscle Contractions

“…As opposed to highly-toxic chemotherapy and radiation therapy regimes, all EBTs are well-tolerated by patients due to a lack of post-procedural complications [5,6]. Because the mechanism of cell death does not rely on thermal processes, outcomes are not subject to heat sink effects from blood perfusion, which can protect tumors from thermal therapies.…”

Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases

“…Solid tumors of various etiologies are being treated successfully. In veterinary medicine several studies have already demonstrated the effectiveness, convenience and safety of ECT with either cisplatin or bleomycin for the treatment of spontaneous tumors, such as soft-tissue sarcomas in cats, mast cell tumors and perianal tumors in dogs and sarcoids in horses [8][9][10][11][12][13][14]. In clinical settings ECT is currently used with palliative intent for the treatment of predominantly melanoma cutaneous metastases, as well as in head and neck tumors, basal cell carcinomas, and adenocarcinomas in humans [15][16][17][18][19][20][21][22][23][24].…”

Electrochemotherapy with intra-tumoral cisplatin for the treatment of fibrosarcoma in a horse

“…The healing of sutured wound edges in the partially resected tumour site without any complications such as wound dehiscence indicated that the settings for the delivery of square wave electric pulses of 100 microseconds, at 1300V/cm, with a frequency of 500Hz was safe and had anti-tumour effect along with cisplatin (Spugnini et al, 2006) without tissue damage and thermal injury. Additionally application of electrical pulses injured the vascular endothelial cells of the tissues surrounding tumours, thus decreasing the flow of blood (vascular lock) resulting in cyto-reduction and tumour cell apoptosis (Bass et al,2017).…”

“…Square wave electric pulses of 100 microseconds, at 1300V/cm, with a frequency of 500Hz was delivered through two parallel stainless steel electrodes attached to therapeutic electroporator machine ( ELECTROvet S13, LEROY Biotech, France). Each run of electric pulses was delivered in 2 trains of 4 pulses, with 1-second interval in first series and the second series was delivered perpendicular to the first direction of electrode placement or in a hexagonal pattern (Spugnini et al, 2006). Good contact between the electrodes and the skin was assured by depilation and application of a conductive gel to the treatment area.…”

“…Cancer cells are sensitive to electrical field than the normal cells. Exposure of cells to high transmembrane potential difference (200 mV) using pulsed electric fields of intensity in the range of 300-3000 V/cm for durations of microseconds (ìs) results in the formation of transient hydrophilic pores which are reversible (Spugnini et al, 2006). Exposure of cells to trains of low electric fields pulsed square waves in the range of 20-100 V/cm leads to efficient uptake of macromolecules with molecular weight in the range of 300-2,000,000 Da into cells (Mir et al, 2006).…”