Electrochemotherapy (ECT) is an innovative treatment method for combating cancer, utilizing a combination of chemotherapy drugs and electrical pulses simultaneously. In this method, a chemotherapy drug such as bleomycin is first administered either intratumorally or intravenously. Then, using an electrochemotherapy device, short, high-intensity electrical pulses are applied to the tumor area, temporarily increasing the permeability of cancer cell membranes. This results in a significant increase in membrane permeability to cytotoxic drugs, thereby enhancing the drug’s lethality on cancer cells. Studies show that the cytotoxic effect of drugs like bleomycin can increase up to 1000-fold in the presence of these pulses. Electrochemotherapy is primarily used for treating superficial and subcutaneous tumors, particularly cutaneous metastases of malignant melanoma and recurrent breast cancer lesions. It is employed when surgery or radiotherapy are not suitable options.
Electrochemotherapy (ECT), also known as electrochemical therapy, is one of the modern and targeted methods in cancer treatment that significantly enhances the efficacy of anticancer drugs by combining chemotherapy with electrical pulses. This method, utilizing electroporation technology, facilitates better penetration of drugs into cancer cells and is particularly effective for treating cutaneous and subcutaneous tumors. Due to its low side effects and the ability to be performed on an outpatient basis, electrochemotherapy has become an attractive option for both patients and physicians. This article comprehensively examines this method, its mechanism of action, applications, side effects, and recent advancements in human cancer treatment, with a brief mention of its application in veterinary medicine at the end.
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What is Electrochemotherapy?
Electrochemotherapy (ECT) can be considered an enhanced localized chemotherapy that uses short, intense electrical pulses to increase the permeability of cancer cell membranes. High-voltage, short-duration electrical pulses cause the cancer cell membranes to temporarily become porous (permeable). This phenomenon, known as “reversible electroporation,” enables chemotherapy drugs such as bleomycin and cisplatin to enter the cells. These drugs typically have difficulty crossing the cell membrane, but electroporation, by creating temporary pores in the membrane, increases their efficacy up to 1000-fold. This results in a higher intracellular concentration of the drug, significantly enhancing its cytotoxic effect. This mechanism allows for local control of cancerous tumors with relatively lower doses of chemotherapy drugs.
This method was developed in Europe in the 1990s and has since been used to treat over 4,000 patients worldwide.
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Mechanism of Action of Electrochemotherapy
Electrochemotherapy operates based on the principle of electroporation. In this method, high-intensity electrical pulses (approximately 400 volts per centimeter) with a short duration (100 microseconds) are applied to the tumor. These pulses create nanometer-sized pores in the cancer cell membranes, enabling chemotherapy drugs to penetrate the cells. For instance, bleomycin, upon entering the cell, acts as an endonuclease enzyme and destroys the DNA of dividing cells.
In addition to the direct effect of the drug, electrochemotherapy has secondary mechanisms:
- Vascular Disruption: Electrical pulses cause constriction of blood vessels in the tumor, reducing blood flow and retaining the drug in the tumor site for an extended period.
- Immune Response: This method stimulates the body’s immune response by releasing tumor antigens, potentially acting as an in-situ vaccine.
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Applications of Electrochemotherapy in Medicine
In recent years, electrochemotherapy has been recognized as an effective and accepted method for treating superficial tumors, cutaneous and subcutaneous metastases of cancers. It is acknowledged in international skin cancer treatment guidelines and is particularly chosen by dermatologists, surgeons, and oncologists for cutaneous tumors. The most common applications include cutaneous metastases of malignant melanoma and breast cancer.
Moreover, phase I/II studies have shown promising results regarding the efficacy of electrochemotherapy in other treatment-resistant cancers, such as head and neck cancer, advanced breast cancer, genital cancers, and colorectal cancer. Overall, electrochemotherapy is a suitable option for patients with inoperable tumors or multiple small lesions that do not respond well to conventional treatments.
However, it should be noted that the application of electrical pulses in electrochemotherapy is limited to a depth of a few centimeters (typically, electrodes cover tumors up to a depth of about 2–3 centimeters). Therefore, for very deep or extensive tumors, other methods such as systemic chemotherapy or surgery may be preferred. Additionally, in patients with sensitivity to the drug used (e.g., intolerance to bleomycin due to pulmonary fibrosis or kidney disease), electrochemotherapy may be contraindicated.
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Types of Cancer Treatable with Electrochemotherapy
As mentioned, electrochemotherapy is widely used for treating cutaneous and subcutaneous tumors. Some of the cancer types treated with this method include:
- Melanoma: Studies have shown a complete response rate of 20 to 50% and an overall response rate of 60 to 100% in melanoma treatment.
- Basal Cell Carcinoma (BCC): This method has shown a complete response rate of up to 63% for BCC.
- Squamous Cell Carcinoma (SCC): ECT has been effective in treating advanced SCC and, in some cases, has prevented disease progression.
- Kaposi’s Sarcoma and Cutaneous Metastases: This method is also used for cutaneous metastases from cancers such as breast cancer.
- Breast Cancer, Cutaneous Metastases: A 2018 study showed a complete response rate of 50%, a partial response rate of 21%, and an overall response rate of 71%.
- Head and Neck Cancer, Cutaneous, Other Histologies: Includes other types of cutaneous tumors (e.g., SCC and melanoma) in the head and neck with an overall response rate of 74%.
- Head and Neck Cancer, Mucosal, Therapeutic: A complete response rate of 80.5% and an overall response rate of 97.2% have been reported in therapeutic settings.
- Head and Neck Cancer, Mucosal, Palliative: A complete response rate of 30.2%, a partial response rate of 41.5%, and an overall response rate of 73.1% have been reported in palliative settings.
- Gastrointestinal Cancer: In one of the treatments by Pars Trava Company, a 40-year-old woman diagnosed with an advanced gastrointestinal stromal tumor (GIST) with abdominal metastases in 2015 underwent electrochemotherapy. After three treatment sessions with the electrochemotherapy device, the tumor volume decreased by 51% compared to its initial volume, considered a partial response (PR).
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Table: Response Rates of Electrochemotherapy in Different Cancer Types
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| Cancer Type | Complete Response Rate (%) | Partial Response Rate (%) | Overall Response Rate (%) |
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| Melanoma (General) | 20–50 | – | 60–100 |
| Basal Cell Carcinoma (General) | Up to 63 | – | Up to 88 |
| Basal Cell Carcinoma (Head and Neck, Cutaneous) | – | – | 97 |
| Squamous Cell Carcinoma (General) | Variable | – | Up to 80 |
| Cutaneous Metastases (General) | Variable | – | Up to 88 |
| Breast Cancer, Cutaneous Metastases | 50 | 21 | 71 |
| Head and Neck Cancer, Cutaneous, Other Histologies | – | – | 74 |
| Head and Neck Cancer, Mucosal, Therapeutic | 80.5 | 16.7 | 97.2 |
| Head and Neck Cancer, Mucosal, Palliative | 30.2 | 41.5 | 73.1 |
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The complete response rate (CR) indicates complete tumor elimination, the partial response rate (PR) indicates significant tumor reduction, and the overall response rate (ORR) is the sum of these two. These metrics help physicians and patients evaluate the effectiveness of treatments such as electrochemotherapy.
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Treatment Process and Procedure
The electrochemotherapy process is typically performed on an outpatient basis and includes the following steps:
- Drug Administration: A chemotherapy drug (e.g., bleomycin or cisplatin) is injected either intravenously or directly into the tumor.
- Waiting for Drug Concentration: After injection, a few minutes are allowed for the drug to reach an optimal concentration in the tumor area (approximately 8 to 10 minutes for intravenous injection).
- Application of Electrical Pulses: Once the drug reaches peak concentration, electrodes are placed on the tumor, and short electrical pulses (e.g., 8 pulses of 100 microseconds with high voltage) are applied to the tumor site.
- Drug Penetration: The drug enters the cancer cells through the compromised membrane, leading to tumor cell death.
- Treatment Repetition: Depending on the size and type of tumor, 1 to 4 treatment sessions may be required, spaced a few weeks apart.
This procedure is typically performed under local anesthesia or general anesthesia, and the patient can return home the same day. Modern electroporation devices allow the use of plate electrodes for superficial tumors and needle electrodes for deeper lesions, enabling optimized pulse delivery based on the tumor’s size and depth.
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Use of Electrochemotherapy in Veterinary Medicine
In addition to human applications, electrochemotherapy has gained attention in veterinary medicine. In many veterinary clinics, ECT is used as a first-line adjunctive treatment for localized tumors in animals (e.g., cutaneous tumors in dogs and cats), enhancing the efficacy of chemotherapy drugs by increasing their uptake into cancer cells.
Electrochemotherapy in veterinary medicine is also used to treat cutaneous and oral tumors in pets such as dogs, cats, and rabbits. This method is effective for treating tumors such as melanoma, mast cell tumors, and soft tissue sarcomas. Clinical results in veterinary medicine have shown that ECT is effective in local tumor control and reducing pain and side effects compared to more invasive methods. A success rate of approximately 90% has been reported.
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Advantages of the Electrochemotherapy Device
Electrochemotherapy offers numerous advantages, including:
- High Efficacy with Preservation of Healthy Tissue: Electrochemotherapy is a localized method that maximizes its effect on cancer cells while causing no thermal damage to surrounding healthy tissues.
- High Therapeutic Response Rate: Studies have shown that a single session of electrochemotherapy can achieve significant therapeutic responses in cutaneous tumors.
- Reduced Pain and Improved Quality of Life: Due to its localized nature and the lack of need for high drug doses, patients often experience less pain compared to systemic chemotherapy or radiotherapy.
- High Safety Profile: Electrochemotherapy has a favorable safety profile; observed side effects are generally limited to the treated area and include mild localized pain, swelling, redness, and occasionally small ulcers.
- No Excessive Heat Generation: Unlike some thermal methods, electrochemotherapy does not produce harmful heat to surrounding tissues, making it suitable for treating lesions near blood vessels and nerves.
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| Parameter | Traditional Methods (Surgery/Chemotherapy) | Electrochemotherapy |
|---|---|---|
| Treatment Precision | Damage to healthy tissues | Targets only tumor cells |
| Side Effects | Hair loss, nausea, immune system suppression | Mild localized side effects (skin redness) |
| Recovery Time | Weeks to months | 24–48 hours |
| Total Treatment Cost | High (long hospitalization, expensive drugs) | 30–40% cost reduction |
| Efficacy in Resistant Tumors | Limited | High efficacy |
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The most significant limitations of electrochemotherapy include the need for specific drugs (e.g., bleomycin) and accessible lesions for electrodes. Additionally, careful monitoring of bleomycin dosage is essential, as high cumulative doses can cause pulmonary side effects. Some patients may not be eligible for this treatment due to pulmonary or renal issues or the presence of electronic devices (e.g., pacemakers).
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Side Effects of Electrochemotherapy and Safety Considerations
Electrochemotherapy, due to the use of low-dose chemotherapy drugs, has fewer side effects compared to traditional chemotherapy. The most common side effects include:
- Localized Side Effects: Redness, swelling, mild ulceration, skin discoloration (which may be permanent), and mild pain at the treatment site.
- Systemic Side Effects: Mild nausea and, in some cases, a feeling of shortness of breath.
- Post-Treatment Care: The treatment site may form a scab and heal within a few weeks. If signs of infection (redness, warmth, discharge) occur, antibiotics may be required.
Studies indicate that this method is generally safe, with serious systemic side effects rarely reported.
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Recent Advances in Electrochemotherapy and Future Prospects
One of the exciting areas in electrochemotherapy is its combination with immunotherapy. Research has shown that ECT can induce immunogenic cell death, which enhances systemic immune responses and increases the effectiveness of immunotherapies, such as checkpoint inhibitors. Limited clinical studies, particularly in melanoma and breast cancer, have shown promising results. For instance, a 2021 study demonstrated that combining ECT with pembrolizumab resulted in higher local response rates and longer progression-free survival.
Additionally, research is exploring the use of electrochemotherapy for internal tumors through surgical, endoscopic, or percutaneous methods. These advancements could expand the scope of this method’s applications.
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Conclusion
Electrochemotherapy, as a modern cancer treatment method, has significant potential for local control of cutaneous and subcutaneous tumors. By combining electroporation with chemotherapy, this method dramatically increases the penetration of anticancer drugs into tumor cells and can be effective even in cases of drug resistance. Clinical results indicate good efficacy of electrochemotherapy in treating cutaneous metastases of melanoma, breast cancer, and other treatment-resistant lesions.
Moreover, due to reduced systemic drug effects and less pain for patients, electrochemotherapy can also improve patients’ quality of life. Although its use is still limited in some internal cancers, ongoing research into its application for various tumor types and in combination with immunotherapy is promising.
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Electrochemotherapy Device by Pars Trava Company
Pars Trava Company is a pioneer in electroporation and electrochemotherapy technology in Iran and, as the first manufacturer of electroporation and electrochemotherapy devices in the country, has taken a significant step toward localizing advanced cancer treatment technologies. Utilizing international standards, the company provides sales and support services for electrochemotherapy equipment.
Pars Trava began its activities in 2021 at the University of Tehran Science and Technology Park and started clinical trials in 2023. The company’s devices have been used in reputable hospitals such as Imam Khomeini Hospital, Amiralmomenin Hospital, Rasoul Akram Hospital, and Shohada Tajrish Hospital in Tehran.
Articles on successful treatment cases using Pars Trava’s electrochemotherapy device are available for review on the company’s website in case studies. Additionally, an internationally published article on cancer treatment with the electrochemotherapy device, conducted by Dr. Shenkai, can be accessed through this link.
For more information or consultation regarding electrochemotherapy devices, you can contact Pars Trava via phone or WhatsApp at +98 902 405 1862.
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References
- Electrochemotherapy: An Alternative Strategy for Improving Therapy in Drug-Resistant SOLID Tumors
- Electrochemotherapy as a New Modality in Interventional Oncology: A Review
- Updated Standard Operating Procedures for Electrochemotherapy of Cutaneous Tumours and Skin Metastases
- Electrochemotherapy for Head and Neck Cancers: Possibilities and Limitations
- frontiersin.org
- Electrochemotherapy in the Treatment of Melanoma
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