Electrochemotherapy Associated with Calcium Electroporation in Metastatic Feline Cutaneous Malignant Melanoma

Authors

  • Denner Santos dos Anjos Department of Veterinary Clinic and Surgery, São Paulo State University (UNESP), Jaboticabal, SP, Brazil.
  • Cecília Gomes Rodrigues Department of Veterinary Clinic and Surgery, São Paulo State University (UNESP), Jaboticabal, SP, Brazil.
  • Nicilene Cardoso Silva Department of Veterinary Clinic and Surgery, São Paulo State University (UNESP), Jaboticabal, SP, Brazil.
  • Andrigo Barboza de Nardi Department of Veterinary Clinic and Surgery, São Paulo State University (UNESP), Jaboticabal, SP, Brazil.
  • Carlos Eduardo Fonseca-Alves Department of Veterinary Clinic and Surgery, São Paulo State University (UNESP), Jaboticabal, SP, Brazil.

DOI:

https://doi.org/10.22456/1679-9216.96498

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 disease free interval of five months when compared to other report of two months. This description showed that ECT associated with CaEP improved outcome of regional melanoma lymph node metastasis in a cat. However, further investigations are needed to understand the use of CaEP in patients for local control metastasis as well as evaluate the use of both modalities to determine its synergistic effect.

Downloads

Download data is not yet available.

References

Eisenhauer E.A., Therasse P., Bogaerts J., Schwartz L.H., Sargent D., Ford R., Dancey J., Arbuck S., Gwyther S., Mooney M., Rubinstein L., Shankar L., Dodd L., Kaplan R., Lacombe D. & Verweij. 2009. New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1). European Journal of Cancer. 45: 228-247.

Calvet C.Y. & Mir L.M. 2016. The promising alliance of anti-cancer electrochemotherapy with immunotherapy. Cancer Metastasis Review. 35: 165-177.

Falk H., Matthiessen L.W., Wooler G. & Gehl J. 2018. Calcium electroporation for treatment of cutaneous metastases; a randomized double blinded phase II study, comparing the effect of calcium electroporation with electrochemotherapy. Acta Oncology. 12: 42.

Falk H., Lambaa S., Johannesen H.H., Wooler G., Venzo A. & Gehl J. 2017. Electrochemotherapy and calcium electroporation inducing a systemic immune response with local and distant remission of tumors in a patient with malignant melanoma - a case report. Acta Oncology. 56(8): 1126-1131.

Frandsen S.K., Gissel H., Hojman P., Eriksen J. & Gehl J. 2014. Calcium electroporation in three cell lines; a comparison of bleomycin and calcium, calcium compounds, and pulsing conditions. Biochimica Biophysica Acta. 1840(3): 1204-1208.

Frandsen S.K., Hansen H.F. & Gehl J. 2016. New Drugs for Electrochemotherapy with Emphasis on Calcium Electroporation. In: Miklavčič D. (Ed). Handbook of Electroporation, Switzerland: Springer International Publishing, pp.1-13.

Frandsen S.K., Gissel H., Hojman P., Tramm T., Eriksen J. & Gehl J. 2012. Direct therapeutic applications of calcium electroporation to effectively induce tumor necrosis. Cancer Research. 72(6): 1336-1341.

Kulbacka J., Paczuska J., Rembialkowska N., Saczko J., Kielbowicz Z., Kinda W., Liszka B., Kotulska M., Kos B., Miklavcic D., Tozon N. & Cemazar M. 2017. Electrochemotherapy combined with standard and CO2 laser surgeries in canine oral melanoma. Slovenian Veterinary Research. 54: 181-186.

Marty M., Sersa G., Garbay J.R., Gehl J., Collins C.G., Snoj M., Billard V., Geertsen P.F., Larkin J.O., Miklavcic D., Pavlovic I., Paulin-Kosir S.M., Cemazar M., Morsli N., Soden D.M., Rudolf Z., Robert C., O’Sullivan G.C. & Mir L.M. 2006. Electrochemotherapy - An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study. European Journal Cancer. 4(11): 3-13.

Milevoj N., Tratar U.L., Nemec A., Brozic A., Znidar K., Sersa G., Cemazar M. & Tozon N. 2019. A combination of electrochemotherapy, gene electrotransfer of plasmid encoding canine IL-12 and cytoreductive surgery in the treatment of canine oral malignant melanoma. Research Veterinary Science. 122: 40-49.

Nishiya A.T., Massoco C.O., Felizzola C.R., Perlmann E., Batschinski K., Tedardi M.V., Garcia J.S., Mendonça P.P., Teixeira T.F.& Zaidan Dagli M.L. 2016. Comparative Aspects of Canine Melanoma. Veterinary Science. 19: E7.

Patnaik A.K. & Mooney S. 1988. Feline melanoma: a comparative study of ocular, oral, and dermal neoplasms. Veterinary Pathology. 25: 105-112.

Plaschke C.C., Gehl J., Johannesen H.H., Fischer B.M., Kjaer A., Lomholt A.F. & Wessel I. 2019. Calcium electroporation for recurrent head and neck cancer: a clinical phase I study. Laryngoscope Investigative Otolaryngology. 4(1): 49-56.

Tozon N., Lampreht T.U., Znidar K., Sersa G., Teissie J. & Cemazar M. 2016. Operating procedures of the electrochemotherapy for treatment of tumor in dogs and cats. Journal of Visualized Experiments. 116: 54760.

van der Linde-Sipman J.S., de Wit M.M.L., van Garderen E., Molenbeek R.F., van der Velde-Zimmermann D. & de Weger R.A. 1997. Cutaneous malignant melanomas in 57 cats: identification of (amelanotic) signet-ring and balloon cell types and verification of their origin by immunohistochemistry, electron microscopy, and in situ hybridization. Veterinary Pathology. 34: 31-38.

Published

2019-01-01

How to Cite

dos Anjos, D. S., Rodrigues, C. G., Silva, N. C., de Nardi, A. B., & Fonseca-Alves, C. E. (2019). Electrochemotherapy Associated with Calcium Electroporation in Metastatic Feline Cutaneous Malignant Melanoma. Acta Scientiae Veterinariae, 47. https://doi.org/10.22456/1679-9216.96498

Most read articles by the same author(s)