a randomized double-blinded phase II study, comparing the effect of calcium electroporation with electrochemotherapy.
Hanne Falk (1), Louise Wichmann Matthiessen (1), Gitte Wooler (2), Julie Gehl (1)
1) Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen. 2) Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen.
Calcium electroporation is a novel anticancer treatment, which utilizes high voltage pulses to permeabilize cell membranes and expose the cell to supraphysiological doses of calcium. Preclinical studies on calcium electroporation have shown strikingly high tumor response with cell necrosis, associated with severe ATP depletion. Calcium electroporation builds on the treatment electrochemotherapy, where chemotherapeutic drugs, mostly bleomycin, are internalized by electroporation. This double blinded randomized study compared calcium electroporation to electrochemotherapy in terms of objective response measured six months after treatment.
Materials and methods
A total of 47 metastases were included in the protocol, six patients had breast cancer and one patient had malignant melanoma. A total of 37 cutaneous metastases were randomized and evaluated for response with six months follow up. Another 10 metastases were biopsied before or one week after treatment. This was a non-inferiority trial and metastases were randomized individually in each patient to either intratumoral calcium or intratumoral bleomycin followed by application of electric pulses to tumor site. All metastases were treated once, and after 6 months follow up, the randomization code was revealed.
Objective response of calcium electroporation was 72.2% (13/18) with complete response in 66.7% (12/18). For electrochemotherapy objective response was 84.2% (16/19) with complete response in 68.4% (13/19). There was no statistically significant difference between the two treatments (p=0.5). At one year follow up of 25 metastases, only three metastases had relapsed. Ulceration, itching and exudating were reported slightly more frequently in metastases treated with bleomycin compared to metastases treated with calcium. Hyperpigmentation was only seen in metastases treated with bleomycin.
This study shows that calcium electroporation is feasible and effective in patients with cutaneous metastases.