Electrochemotherapy Associated with Calcium Electroporation in Metastatic Feline Cutaneous Malignant Melanoma

Abstract

Background: Calcium electroporation (CaEP) is a novel therapeutic treatment that has been studied for cancer due to its selective killing cancer cells by necrosis and danger signals. Besides that, electrochemotherapy (ECT) is an effective local treatment that involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumor. The combination with ECT and CaEP has been reported in literature suggesting that additional response of immune system could have been enhanced by electroporation with calcium. This case, report on the successful treatment with CaEP combined with ECT for treatment of a regional metastasis in a feline model of malignant melanoma. Case: A 9-year-old, mixed breed cat was referred to the veterinary clinic with a 2-month history of cutaneous peripalpebral plaque lesion (0.19 cm³) and a submandibular lymph node enlargement (0.5 cm³). Incisional biopsy of the cutaneous lesion and fine-needle aspiration of submandibular lymph node confirmed a cutaneous melanoma with submandibular lymph node metastasis. Tumor staging was set in T1N1M0 according to WHO staging criteria. ECT for the primary lesion and lymph node metastasis was proposed. For the ECT, bleomycin (15,000 UI/m²) application was performed intravenous followed by electroporation (8 pulses of 100 μs at 1000 V/cm, and 1 Hz) using a needle array electrode consisted of two parallel rows with six needles in each row. At 28-day post-ECT complete remission of the primary tumor and metastatic foci was achieved. However, 120 days after ECT, recurrence was observed in submandibular and retropharyngeal lymph nodes. A second ECT approach was performed adding to bleomycin the intra lymph nodal application of calcium gluconate. The dose of calcium gluconate was diluted in an isotonic 0.9% NaCl solution resulting in a low concentration at 9 mM, injected in both metastatic lymph nodes (submandibular total volume: 1.4 ml; retropharyngeal total volume: 0.5 mL) and pulses were delivered immediately after drug administration. No systemic adverse effects were observed. Local adverse effects were considered mild as transitory edema and ulceration post procedure. One-week post-ECT+CaEP, complete remission of local metastasis occurred. However, the patient achieved five months disease free interval, and died during a surgical approach, achieving nine months of survival time. Discussion: Feline cutaneous malignant melanoma is an aggressive disease with a short survival time for the patients with mean of 4.5 months. CaEP is a novel anticancer treatment that has been study in the past years due to its selective killing cancer cells by necrosis and danger signals. The CaEP induces supraphysiological calcium influx into neoplastic cells leading to acute ATP depletion and necrosis of tumor cells. This use could be an interesting therapeutic choice for both human and veterinary medicine. In this patient, it was demonstrated a good clinical response with its use, showing temporarily tumor remission from the case presented with disea...

A Comprehensive Review of Calcium Electroporation—A Novel Cancer Treatment Modality

“…Unfortunately, the dog was euthanized two months after diagnosis due to brain metastases. In the case with a feline melanoma [117], the tumor was treated with electrochemotherapy with good effect but recurrence occurred three months after treatment. Two metastases were treated with electroporation in combination with both bleomycin and a low calcium dose (9 mM), thus electrochemotherapy combined with calcium.…”

Electrochemotherapy as a treatment option for feline nasal melanoma

“…CaEP causes calcium influx at supra-physiological levels into neoplastic cells, causing cell death by necrosis. 18 The combination of these two novel cancer treatment modalities requires further investigations to understand their synergistic effect. That case suggests that both ECT and CaEP may be effective treatments for cutaneous melanoma in cats and, given the favourable response also seen in this case report, indicates further investigation of ECT as a treatment option for feline cutaneous melanoma.…”