CC BY-NC-ND 4.0 · Endosc Int Open 2020; 08(02): E124-E132
DOI: 10.1055/a-1027-6735
Original article
Owner and Copyright © Georg Thieme Verlag KG 2020

Electrochemotherapy for colorectal cancer using endoscopic electroporation: a phase 1 clinical study

Hanne Falk Hansen
 1   Center for experimental drug and gene electrotransfer (C*EDGE), Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
,
Michael Bourke
 2   Cork Cancer Research Centre, University College Cork, Ireland
,
Trine Stigaard
 3   Gastro Unit, Department of Surgical Gastroenterology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
,
James Clover
 2   Cork Cancer Research Centre, University College Cork, Ireland
,
Martin Buckley
 4   Gastroenterology Department, Mercy University Hospital, Cork, Ireland
,
Micheal O’Riordain
 5   Department of Surgery, Mercy University Hospital, Cork, Ireland
,
Des C. Winter
 6   Centre for Colorectal Disease, St Vincent’s University Hospital, Dublin, Ireland 
,
Helle Hjorth Johannesen
 7   Department of Radiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
,
Rasmus Hvass Hansen
 7   Department of Radiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
,
Hanne Heebøll
 7   Department of Radiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
,
Patrick Forde
 2   Cork Cancer Research Centre, University College Cork, Ireland
,
Henrik Loft Jakobsen
 3   Gastro Unit, Department of Surgical Gastroenterology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
,
Ole Larsen
 8   Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen. Denmark
,
Jacob Rosenberg
 3   Gastro Unit, Department of Surgical Gastroenterology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
10   Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
,
Declan Soden
 2   Cork Cancer Research Centre, University College Cork, Ireland
,
Julie Gehl
 1   Center for experimental drug and gene electrotransfer (C*EDGE), Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
 9   Center for Experimental Drug and Gene Electrotransfer (C*EDGE), Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Roskilde, Denmark
10   Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
› Author Affiliations
Further Information

Publication History

submitted 12 April 2019

accepted after revision 16 July 2019

Publication Date:
22 January 2020 (online)

Abstract

Background and study aims Electrochemotherapy is an anticancer treatment that uses electric pulses to facilitate uptake of chemotherapeutic drugs in tumor cells and has proven to have a high local cytotoxic effect with minimal adverse events. Electrochemotherapy has mostly been used in treatment of cutaneous metastases but development of a new endoscopic electrode device has made treatment of colorectal tumors possible. This first-in-man multicenter phase I study investigated safety and efficacy of electrochemotherapy using endoscopic electroporation in patients with colorectal tumors.

Patients and methods Seven patients with colorectal tumors who were deemed ineligible for or had declined standard treatment were included. They were treated with bleomycin either intratumorally or intravenously and the electric pulses were delivered through the endoscopic electrode device. Safety and efficacy were assessed clinically and by scans immediately after treatment and adverse events were reported. Response was evaluated up to 6 months after treatment by scans (magnetic resonance imaging or computed tomography) and endoscopic examinations.

Results Seven patients aged 62 to 88 years with multiple comorbidities were included and had one or two treatments each. Post-treatment scans showed tumor responses in the treated areas and no damage to surrounding tissues. Only a few grade one adverse events were reported. Three patients had preoperative rectal bleeding, of which two reported cessation of bleeding and one reported decreased bleeding.

Conclusion This first-in-man study shows that electrochemotherapy for colorectal tumors using the endoscopic electrode device can induce local tumor response and is safe also for fragile elderly patients with comorbidities.

 
  • References

  • 1 Torre LA, Bray F, Siegel RL. et al. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65: 87-108
  • 2 Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin 2014; 64: 104-117
  • 3 Mir LM, Orlowski S. Mechanisms of electrochemotherapy. Adv Drug Deliv Rev 1999; 35: 107-118
  • 4 Mir LM. Bases and rationale of the electrochemotherapy. EJC Suppl 2006; 4: 38-44
  • 5 Yarmush ML, Golberg A, Sersa G. et al. Electroporation-based technologies for medicine: principles, applications, and challenges. Annu Rev Biomed Eng 2014; 16: 295-320
  • 6 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
  • 7 Orlowski S, Belehradek Jr. J, Paoletti C. et al. Transient electropermeabilization of cells in culture. Increase of the cytotoxicity of anticancer drugs. Biochem Pharmacol 1988; 37: 4727-4733
  • 8 Gehl J, Skovsgaard T, Mir LM. Enhancement of cytotoxicity by electropermeabilization: an improved method for screening drugs. Anticancer Drugs 1998; 9: 319-325
  • 9 Jaroszeski MJ, Dang V, Pottinger C. et al. Toxicity of anticancer agents mediated by electroporation in vitro. Anticancer Drugs 2000; 11: 201-208
  • 10 Marty M, Sersa G, Garbay JR. et al. Electrochemotherapy - An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: Results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study. EJC Suppl 2006; 4: 3-13
  • 11 Matthiessen LW, Chalmers RL, Sainsbury DC. et al. Management of cutaneous metastases using electrochemotherapy. Acta Oncol 2011; 50: 621-629
  • 12 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
  • 13 Belehradek M, Domenge C, Luboinski B. et al. Electrochemotherapy, a new antitumor treatment. First clinical phase I-II trial. Cancer 1993; 72: 3694-3700
  • 14 Campana LG, Mocellin S, Basso M. et al. Bleomycin-based electrochemotherapy: clinical outcome from a single institution's experience with 52 patients. Ann Surg Oncol 2009; 16: 191-199
  • 15 Curatolo P, Quaglino P, Marenco F. et al. Electrochemotherapy in the treatment of Kaposi sarcoma cutaneous lesions: a two-center prospective phase II trial. Ann Surg Oncol 2012; 19: 192-198
  • 16 Heller R, Jaroszeski MJ, Reintgen DS. et al. Treatment of cutaneous and subcutaneous tumors with electrochemotherapy using intralesional bleomycin. Cancer 1998; 83: 148-157
  • 17 Kis E, Olah J, Ocsai H. et al. Electrochemotherapy of cutaneous metastases of melanoma--a case series study and systematic review of the evidence. Dermatol Surg 2011; 37: 816-824
  • 18 Quaglino P, Mortera C, Osella-Abate S. et al. Electrochemotherapy with intravenous bleomycin in the local treatment of skin melanoma metastases. Ann Surg Oncol 2008; 15: 2215-2222
  • 19 Clover AJP, Bertino G, Curatolo P. et al. Electrochemotherapy in the treatment of cutaneous malignancy; outcomes and subgroup analysis from the cumulative results from the pan- European InspECT Database for 1478 lesions in 691 patients (2008-2018). Budapest: ESSO38 (European Society of Surgical Oncology, 38th Congress); 2018
  • 20 Matthiessen LW, Chalmers RL, Sainsbury DC. et al. Management of cutaneous metastases using electrochemotherapy. Acta Oncol 2011; 50: 621-629
  • 21 Benevento R, Santoriello A, Perna G. et al. Electrochemotherapy of cutaneous metastastes from breast cancer in elderly patients: a preliminary report. BMC Surg 2012; 12 (Suppl. 01) S6
  • 22 Linnert M, Iversen HK, Gehl J. Multiple brain metastases – current management and perspectives for treatment with electrochemotherapy. Radiol Oncol 2012; 46: 271-278
  • 23 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
  • 24 Campana LG, Edhemovic I, Soden D. et al. Electrochemotherapy - Emerging applications technical advances, new indications, combined approaches, and multi-institutional collaboration. Eur J Surg Oncol 2019; 45: 92-102
  • 25 Miklavcic D, Sersa G, Brecelj E. et al. Electrochemotherapy: technological advancements for efficient electroporation-based treatment of internal tumors. Med Biol Eng Comput 2012; 50: 1213-1225
  • 26 Forde PF, Sadadcharam M, Bourke MG. et al. Preclinical evaluation of an endoscopic electroporation system. Endoscopy 2016; 48: 477-483
  • 27 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
  • 28 Karnofsky DA, Abelmann WH, Craver LF. et al. The use of the nitrogen mustards in the palliative treatment of carcinoma – with particular reference to bronchogenic carcinoma. Cancer 1948; 1: 634-656
  • 29 Gehl J, Sersa G, Matthiessen LW. et al. Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases. Acta Oncol 2018; 57: 874-882
  • 30 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. EJC Suppl 2006; 4: 14-25
  • 31 Markelc B, Sersa G, Cemazar M. Differential mechanisms associated with vascular disrupting action of electrochemotherapy: intravital microscopy on the level of single normal and tumor blood vessels. PLoS One 2013; 8: e59557
  • 32 Sersa G, Cemazar M, Miklavcic D. et al. Tumor blood flow modifying effect of electrochemotherapy with bleomycin. Anticancer Res 1999; 19: 4017-4022
  • 33 Jarm T, Cemazar M, Miklavcic D. et al. Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases. Expert Rev Anticancer Ther 2010; 10: 729-746
  • 34 Egeland C, Baeksgaard L, Johannesen HH. et al. Endoscopic electrochemotherapy for esophageal cancer - a phase I clinical study. Endosc Int Open 2018; 6: E727-E734
  • 35 Falk H, Forde PF, Bay ML. et al. Calcium electroporation induces tumor eradication, long-lasting immunity and cytokine responses in the CT26 colon cancer mouse model. Oncoimmunology 2017; 6: e1301332