Evaluation of Calcium Electroporation for the Treatment of Cutaneous Metastases: A Double Blinded Randomised Controlled Phase II Trial

Abstract

Calcium electroporation (Ca-EP) is a new anticancer treatment providing similar features to electrochemotherapy (ECT). The aim of our study is to compare the efficacy of Ca-EP with bleomycin-based ECT. This double-blinded randomized controlled phase II study was conducted at the Medical University of Szeged, Hungary. During this once only treatment up to ten measurable cutaneous metastases per patient were separately block randomized for intratumoral delivery of either calcium or bleomycin, which was followed by reversible electroporation. Tumour response was evaluated clinically and histologically six months after treatment. (ClinicalTrials.gov: NCT03628417, closed). Seven patients with 44 metastases (34 from malignant melanoma, 10 from breast cancer) were included in the study. Eleven metastases were taken for biopsies, and 33 metastases were randomised and treated once. The objective response rates were 33% (6/18) for Ca-EP and 53% (8/15) for bleomycin-based ECT, with 22% (4/18) and 40% (6/15) complete response rates, respectively. The CR was confirmed histologically in both arms. Serious adverse events were not registered. Ulceration and hyperpigmentation, both CTCA criteria grade I side effects, were observed more frequently after bleomycin-based ECT than for Ca-EP. Ca-EP was non-inferior to ECT, therefore, it should be considered as a feasible, effective and safe treatment option.

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

“…A confirmatory trial based on the same protocol as the first clinical trial [19] has included 7 patients with cutaneous metastases from malignant melanoma (six patients) and breast cancer (one patient) [121]. Similar calcium concentrations were used, however both linear and hexagonal electrodes were used in this study (only linear in the first clinical study).…”

Calcium Electroporation of Equine Sarcoids

“…Thus, viable treatment options, where practical and financial aspects are taken into account, are needed. Calcium electroporation is a simple and inexpensive local tumor treatment, proven safe and efficient in human clinical trials on patients with cutaneous metastases from breast cancer and malignant melanoma [3,18], as well as on the recurrent and mucosal head and neck cancer [6]. In a recent study, calcium electroporation was tested on equine sarcoids, where short-term effects of the treatment were observed with calcium electroporation performed preoperatively [15].…”

Electric Field Based Therapies in Cancer Treatment

“…This Special Issue covers a number of hot topics in the field of electric field based therapies in cancer treatment. Original research and a review article present recent advances in calcium electroporation [ 11 , 12 , 13 , 14 ], the potential of expandable electrodes is presented in a porcine model undergoing open body surgery, laparoscopy and endoscopy [ 15 ], and the extension of the time of blood brain barrier disruption is highlighted after application of high frequency electroporation [ 16 ]. In addition to a review providing the state of the art in cytoskeletal alterations after electroporation [ 17 ], original research articles also present the induction of immunogenic cell death by nanosecond pulsed electric fields [ 18 ] and describe protocols for the optimization of DNA electrotransfer [ 19 , 20 ].…”

“…This approach has been used in clinics and the treatment modality is thoroughly reviewed by Frandsen et al [ 14 ]. In addition to this comprehensive review, Agoston et al [ 12 ] presented a Phase II Clinical trial (NCT03628417) where they compared the efficacy of calcium-based electroporation with bleomycin-based electrochemotherapy. The two approaches lead to a similar tumor response but adverse reactions, such as ulceration and hyperpigmentation, were less common after calcium-based electroporation [ 12 ].…”

“…In addition to this comprehensive review, Agoston et al [ 12 ] presented a Phase II Clinical trial (NCT03628417) where they compared the efficacy of calcium-based electroporation with bleomycin-based electrochemotherapy. The two approaches lead to a similar tumor response but adverse reactions, such as ulceration and hyperpigmentation, were less common after calcium-based electroporation [ 12 ]. Moreover, as highlighted by Gibot et al [ 13 ], calcium electroporation is not genotoxic.…”