Endoscopic Electroporation for Colorectal Cancer: Enhancing drug absorption

Declan M Soden, PhD, Patrick Forde, PhD, Mira Sadadcharam, MD, Michael Bourke, MD, Gerald C O’Sullivan, MB, MCh, MSc, FRCSI

University College Cork

The EndoVe system has been developed at the Cork Cancer Research Centre and allows for the endoscopic facilitated targeted treatment of colorectal tumors. It functions by applying a brief electric/electroporation pulse (around 1mSec) to the tumor. Using optimized electroporation pulses can enhance local tissue permeability by up to a 1000 fold, greatly facilitating the tumor absorption of certain poorly permeable chemotherapy drugs. Drugs may be delivered intravenously or intratumorally and as drug absorption by the tumor is more effective the concentrations required are substantially reduced and limited to a single session outpatient colonoscopy type procedure.

Drug absorption largely occurs only in the area around the tumor that has been electroporated with the EndoVe. One of the significant advantages of the system is that healthy cells and tissues surrounding the tumour are selectively less sensitive than the cancer cells to the treatment. The higher conductivity of tumor tissue makes it more sensitive to electroporation while healthy cells in the margins have a greater capacity to recover from the stress (restore membrane function and ATP levels). A small percentage of healthy cells may undergo apoptosis but a significant inflammatory reaction is not induced. Importantly the approach also enables an enhanced immune response to occur with an increase in antigen presenting cells and cytotoxic T cells present at the site after treatment.

This approach using electroporation to facilitate drug absorption for cancer treatment has become established in the treatment of skin cancers and is referred to as electrochemotherapy. The application of electroporation with bleomycin to skin tumors has been demonstrated to result in up to a 10-fold log increase in the intracellular concentration of bleomycin. Systemic toxicity and collateral injury is minimal as cytotoxicity is restricted to the tissues covered by the applied electrical field. Because the resulting cell death is by apoptosis there is minimal inflammatory reaction or systemic illness during involution of the tumor.

The treatment is minimally disturbing for patients, is easy to perform in an outpatient setting and significantly supports an improvement in quality of life. The real potential for this treatment however may exist through facilitating a minimally invasive approach to intraluminal tumor resolution and this has consequently led to the development of the EndoVe device. The endoscopic attachment was designed to facilitate the treatment of internal cancers and a significant amount of preclinical large animal data has been prepared which demonstrates a significant opportunity for patient care.

The treatment of spontaneous canine colorectal cancers has demonstrated the EndoVe device to be effective and safe with complete tumor ablation noted in all the cases treated. All procedures were conducted as a simple colonoscopy type procedure with no adverse side effects recorded. A Phase I/II clinical trial was approved by the Irish Medicines Board and early clinical experience has demonstrated this technology to have significant potential in the management of surgically complicated cases.
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Session: Poster Presentation

Program Number: ETP027