Electrochemotherapy in human medicine

A group of specialists located in four medical centers – University of Copenhagen (Herlev Hospital, Herlev, Denmark), Institute of Oncology (Ljubljana, Slovenia), Institut Gustave-Roussy (Villejuif, France) and Cork Cancer Research Centre (Cork, Ireland) – have developed European standard operational procedures for use of electrochemotherapy (ECT) on humans, named ESOPE (European Standard Operating Procedures for Electrochemotherapy).

NICE guidelines (UK) recommend treating primary basal cell carcinomas and squamous cell carcinomas with ECT.

To date, more than 180 human clinics are equipped with ECT.

When is ECT used?

The main use of ECT is the curative treatment of cutaneous and subcutaneous tumor nodules, when other methods, such as radiotherapy, chemotherapy, or surgery, have failed or are inadequate.

Benefits

Direct injection of therapeutic molecules into cells is considered the simplest method for delivering drugs. For more than 10 years now, development of methods targeting tumors or drug diffusion in cancer treatment have become prominent in bio-medical research, in order to increase the beneficial effects of drugs and reduce adverse effects.

For 25 years, electroporation has proven its safety and efficacy for delivering nucleic acids (DNA plasmid, siRNA, antisense RNA), proteins (antibodies) and anti-tumor drugs (cisplatin, bleomycin) through the plasma membrane.

Main advantages

  • Improvement in quality of life for patients, regardless of life expectancy
  • Healing of painful or bleeding tumors
  • Improvement of esthetic results
  • Preservation of organ function
  • Possibility of curing isolated lesions

Contraindications

According to ESOPE procedures, the only conditions for which ECT treatment is forbidden are reduced kidney function, and/or a cardiac arrhythmia or presence of a pacemaker when the lesions are located on the chest.

In addition, previous exposure to bleomycin (more than the maximum recommended dose) and pulmonary fibrosis prohibit the use of bleomycin.

Success rates

Overall, response to ECT treatment has been succesful in humans for cases of breast cancer, head and neck tumors, Kaposi’s sarcoma, renal cell carcinoma, chondrosarcoma, and basal cell carcinoma.

A systematic review of published results since 1993 (1,894 tumors in total) was conducted by Miklavcic in 2013. After one session of ECT, efficiency is estimated at an 84.1% objective response, including a 59.4% complete response, regardless of tumor type. These results were compared to the administration of single-agent chemotherapy, which showed a 19.9% objective response rate. This study also showed that there is no significant difference between intratumoral injections of bleomycin and cisplatin (as already shown in an ESOPE report). ECT treatment appears more effective on non-melanoma tumors (86.4% OR) than melanomas (80.6% OR). Similarly, ECT appears to be more effective in sarcomas than carcinomas.

Response to the treatment depends on the tumor size. In an Italian study from 2009 (LG Campana) on 52 patients, 66% had a complete response for tumors smaller than 1.5cm, 36% if the tumor measured 1.6 to 3cm, and 28% if it measured more than 3cm. They thus showed that the smaller the tumor, the better the response.

Side effects observed in humans

Muscle contractions occur after application of the electric field. This contraction is localized, resulting in a sensation of shock and stops at the end of the pulses.

This contraction is more intense when the tumor is located on the face of or near the nerve plexus. According to one study (Mir, 2006), 93% of people who have already been treated with ECT accept a new treatment, if deemed necessary.

No serious general side effects related to ECT have been described. Pain after treatment is considered to be “moderate” by patients.

However, immediate minor effects were observed, such as irritation and an unpleasant or painful sensation associated with muscle contractions that reach the vicinity of the electrodes, which directly decreases after local anesthesia.

In addition, some delayed side effects may appear during necrosis of the tumor. Edema and erythema resolved in 24 hours was noted (Mir 1998). Persistent scabbing for two to four weeks has also been described. All of these side effects are local, temporary, minimal and well tolerated by patients. ECT does not require overnight hospitalization.

Would you like to try
electrochemotherapy in your clinic ?