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

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.

Conflict of interest statement

Competing interests Dr. Soden reports a conflict of interest regarding a patent on the EndoVe electrode as well as owner interests in Mirai Medical.

Figures

Fig. 1 a

Illustration of the endoscopic vacuum electrode (EndoVe), an electrode developed to attach to a standard endoscope and vacuum system.bIllustration of the treatment head; a chamber approximately 2.5 cm 3 containing two plate electrodes .cIllustration of the EndoVe device in colon. The treatment head is placed on tumor tissue which is drawn by negative pressure into the electrode chamber allowing application of the electric field. Source: Cork Cancer Research Centre

Fig. 2

Timeline illustrating treatment plan and follow-up for patients treated at Mercy University Hospital, Cork Ireland and Herlev hospital, University of Copenhagen, Denmark. Additional scans were performed immediately after treatment and at 4-month follow-up at Herlev Hospital.

Fig. 3

Pre and post treatment CT scans from patient no. 5.CT evaluation from patient no. 5 treated at Herlev hospital, University of Copenhagen, Denmark. The patient only had one treatment. Baseline: Shows a rectal tumor, mainly on the posterior wall with maximum measurements of 3.6 × 5.9 cm and a craniocaudal extension of 5.3 cm. Treatment day: Performed a few hours after the procedure and shows no change in tumor volume but massive edema of the treated area. There is no free fluid, no sign of perforation and surrounding intestinal loops appear unaffected. One-month follow- up: Shows decreasing tumor 1.5 × 3.2 cm and craniocaudal extension 4.3 cm. There is still edema of the mucosa. Surrounding intestinal loops still unaffected. Five-month follow-up: Shows marked increase of tumor volume with mechanical obstruction of colon.

Fig. 4

Pre- and post-MRI from patient no. 6. MR evaluation from patient no. 6 treated at Herlev hospital, Denmark. The patient had two treatments. Baseline: MRI shows a circumscript rectum tumor, thickest part 1.5 cm. Treatment day: MRI a few hours after first treatment. Only the right lateral wall was treated. The MRI shows edema in treated area. 1 month after treatment: One-month follow-up after initial treatment MRI shows decrease of tumor in the treated area. Three months after treatment: Two months after initial treatment, the patient was retreated to cover tumor in the left lateral wall. The MRI is 1 month after the second treatment and 3 months after the first treatment. The scan shows a decrease in the newly treated area but a progression in the right lateral wall.

Fig. 5

Pictures from endoscopic examination before and after treatment. Endoscopic pictures from patient no. 7 treated at Herlev hospital, Denmark. Baseline picture shows a rectal tumor estimated 3 × 2 cm. Six weeks after treatment there is a necrotic tumor decreased in size and surrounded by fibrotic tissue.