Endoscopic electrochemotherapy for esophageal cancer: a phase I clinical study

Abstract

Background and study aims Esophageal cancer is on the rise in the western world and the disease has a poor 5-year survival prognosis below 20 %. Electrochemotherapy is a treatment where a chemotherapeutic drug is combined with locally applied electrical pulses, in order to increase the drug’s cytotoxicity in malignant cells. This study presents the first results with electrochemotherapy treatment in esophageal cancer.

Patients and methods In this first-in-human trial, six patients with advanced esophageal cancer were treated with electrochemotherapy using intravenous bleomycin. All side effects and adverse events (AEs) were registered and the patients were later evaluated with gastroscopy and 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI).

Results Treatment were well tolerated, main AEs being nausea, vomiting, oral thrush, pneumonia, retrosternal pain, fever, and hoarseness. No serious complications were observed. Five patients had a visual tumor response confirmed by gastroscopy. In two cases, these findings were confirmed with 18F-FDG PET/MRI as it revealed a reduction of total tumor mass.

Conclusion Electrochemotherapy in patients with advanced esophageal cancer was conducted without major safety concerns. This study paves the way for larger studies, which may further elucidate response rates for and side effects of this new treatment.

• References

• 1 World Health Organization. Globocan 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. 2012 Available from: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx [Accessed: 2017 May 01]
• 2 Javle M, Ailawadhi S, Yang GY. et al. Palliation of malignant dysphagia in esophageal cancer: a literature-based review. J Support Oncol 2006; 4: 365-73, 379
• 3 American Cancer Society. Palliative therapy for cancer of the esophagus. Avaible from: https://www.cancer.org/cancer/esophagus-cancer/treating/palliative-therapy.html [Accessed: 2017 May 17]
• 4 Sersa G, Miklavcic D, Cemazar M. et al. Electrochemotherapy in treatment of tumours. Eur J Surg Oncol 2008; 34: 232-40
• 5 Mir LM, Gehl J, Sersa G. et al. Standard operating procedures of the electrochemotherapy: instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by the CliniporatorTM by means of invasive or non-invasive electrodes. Eur J Cancer 2006; 4: 14-25
• 6 Gehl J, Skovsgaard T, Mir LM. Enhancement of cytotoxicity by electropermeabilization: an improved method for screening drugs. Anticancer Drugs 1998; 9: 319-325
• 7 Tounekti O, Pron G, Belehradek JJr. et al. Bleomycin, an apoptosis-mimetic drug that induces two types of cell death depending on the number of molecules internalized. Cancer Res 1993; 53: 5462-5469
• 8 Belehradek M, Domenge C, Luboinski B. et al. Electrochemotherapy, a new antitumor treatment. First clinical phase I-II trial. Cancer 1993; 72: 3694-3700
• 9 Gothelf A, Mir LM, Gehl J. Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation. Cancer Treat Rev 2003; 29: 371-387
• 10 Bertino G, Sersa G, De Terlizzi F. et al. European research on electrochemotherapy in head and neck cancer (EURECA) project: results of the treatment of skin cancer. Eur J Cancer 2016; 63: 41-52
• 11 Matthiessen LW, Johannesen HH, Hendel HW. et al. Electrochemotherapy for large cutaneous recurrence of breast cancer: a phase II clinical trial. Acta Oncol 2012; 51: 713-721
• 12 Landstrom FJ, Nilsson CO, Reizenstein JA. et al. Electroporation therapy for T1 and T2 oral tongue cancer. Acta Otolaryngol 2011; 131: 660-664
• 13 Landstrom FJ, Reizenstein J, Adamsson GB. et al. Long-term follow-up in patients treated with curative electrochemotherapy for cancer in the oral cavity and oropharynx. Acta Otolaryngol 2015; 135: 1070-1078
• 14 Gargiulo M, Papa A, Capasso P. et al. Electrochemotherapy for non-melanoma head and neck cancers: clinical outcomes in 25 patients. Ann Surg 2012; 255: 1158-1164
• 15 Edhemovic I, Gadzijev EM, Brecelj E. et al. Electrochemotherapy: a new technological approach in treatment of metastases in the liver. Technol Cancer Res Treat 2011; 10: 475-485
• 16 Girelli R, Prejanò S, Cataldo I. et al. Feasibility and safety of electrochemotherapy (ECT) in the pancreas: a pre-clinical investigation. Radiol Oncol 2015; 49: 147-154
• 17 Mellow MH, Pinkas H. Endoscopic therapy for esophageal carcinoma with Nd:YAG laser: prospective evaluation of efficacy, complications, and survival. Gastrointest Endosc 1984; 30: 334-339
• 18 Oken MM, Creech RH, Tormey DC. et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5: 649-655
• 19 International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use (ICH). ICH harmonised tripartite guideline: guideline for good clinical pratice 1996. 1996 Available from: https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_Guideline.pdf [Accessed: 2017 Mar 10]
• 20 Common terminology criteria for adverse events (CTCAE). Available from: https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf [Accessed: 2018 Jan 01]
• 21 Rotunno R, Campana LG, Quaglino P. et al. Electrochemotherapy of unresectable cutaneous tumours with reduced dosages of intravenous bleomycin: analysis of 57 patients from the International Network for Sharing Practices of Electrochemotherapy registry. J Eur Acad Dermatol Venereol 2017; [Epub ahead of print 2017 Nov 24]
• 22 Falk HansenH, Stigaard T, Clover J. et al. Electrochemotherapy for colo-rectal cancer using endoscopic electroporation; A phase I clinical study. Unpublished results.