PetCancerVet

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ELECTROCHEMOTHERAPY - ECT.

• How it works.
• Warning.
• Types of case likely to benefit.
• Examples

One problem with chemotherapy is getting the cytotoxic drugs into the cells. This especially applies to larger drug molecules. Research into gene therapy has led to the discovery that it is possible to open 'pores' in the membranes of cells which can allow larger molecules to enter. This technique is beginning to be used in treatment of cancer in humans and some work has been done in dogs and cats.

The cell membranes are made porous by the application of very short, square wave electrical pulses through tissue. This can be done using special equipment which has been in use at PetCancerVet since November 2004. The company which manufactures the equipment, CytoPulse Inc, is interested to develop veterinary use of electrochemotherapy (ECT) and we will be working with them on design of electrodes for veterinary use.

A drug called Bleomycin has been used most widely in ECT. It is extremely toxic to tumour cells but, because it is a large molecule, many tumour cells do not allow it to enter. ECT increases the amount of Bleomycin entering cells by 300 to 700 times.

Small tumours can be injected directly with Bleomycin before ECT; patients with larger or multiple tumours can have Bleomycin injected into their circulation. In either case, ECT will increase the effect of the drug in killing cells in the tumours receiving ECT markedly.

An excellent introductory reference is Gothelf, Mir and Gehl, Cancer Treatment Reviews 2003 Vol 29, pages 371-387

*** WARNING ***

It is important to note that ECT is a very new and relatively untried treatment method but published evidence suggests that it would be useful in treating patients which would otherwise need unpleasant surgery. If the tumour is likely to spread elsewhere, ECT will not affect that but may give palliation from the effects of the primary tumour. Also, tumours within bones are not currently amenable to treatment with ECT.

Examples where ECT might be valuable:

• Fibrosarcoma in the mouth or eyelid.
• Melanoma in the mouth, eyelid or paw.
• Squamous cell carcinoma in mouth, eyelid or paw.
• Haemangiopericytoma where surgical treatment would necessitate amputation.
• Cat dorsal shoulder fibrosarcoma (Mir et al, British Journal of Cancer (1997), 76(12), 1617-1622).
• Low to intermediate grade mastocytomas on distal limb and face.
• Operation site margins where there is a significant risk of remaining tumour tissue.
• Perianal tumours can be treated with only minor and temporary disturbance to defaecation.
• Other tumours where surgery would result in unreasonable disability or deformity not acceptable to the owners but PLEASE NOTE: this does not include primary tumours involving major bones such as osteosarcoma.

Another veterinary reference (using cisPlatin, not Bleomycin) is:
Tozon, Sersa and Cemazar, Anticancer Research 2001,Vol 21, pages 2483-2496.

Experiences in the first 2 years of use.

From November 2004 to February 2007 56 cases have been treated. The most commonly treated have been squamous cell carcinomas of the face and mouth, with 80% complete remissions and operation site margins for mast cell tumours and soft tissue sarcomas where it will need another 2 years to assess success though some patients were treated in early 2005 and are still in full remission. Small mast cell tumours found on some of these dogs have responded completely to a single treatment but larger ones have not. A recent case of mast cell tumour on a dog's upper lip was treated twice and appears to have achieved remission.

Squamous cell carcinoma in dog's mandible

A 9 year old Terrier X cross developed a mass amongst her lower incisor teeth.The 'normal' treatment for this would be surgery to remove the front part of her jaw: she would lose her lower jaw to behind her canine teeth and her tongue would dangle. Her owners were very reluctant to have this operation done. Radiotherapy might have killed the tumour but there would be significant risk of damage to normal tissues in the region. She was treated with ECTafter extraction of the teeth in the affected part of the jaw.

After 3.5 months, with no side-effects, her mouth has healed beautifully . It is now more than 2 years since she was treated and there has been no sign of the tumour. Many dogs with this type of tumour would have been put to sleep within a few weeks of diagnosis.

Synovial cell sarcoma in an old dog

This tumour appeared on the elbow of an 18 year old Border terrier and was invading the skin. The lesion was approaching the point of ulceration and surgery would have had to be radical to have a chance of local cure. Such surgery would have been disabling and there might have been significant healing problems.

The lesion was infiltrated with Bleomycin and ECT was applied under general anaesthesia. The dog was slightly lame for a few days, but soon returned to normal exercise. The tumour became necrotic after 6 days and after 10 days the dead tissue sloughed away.

After 25 days the resulting ulcer was beginning to heal . The dog was not distressed by the presence of the ulcer.

After 6 weeks the ulcer had almost healed.

Five months after treatment there is no evidence of tumour and only minimum scarring.

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Fibrosarcoma in cat's paw

This cat had previously had 2 fibrosarcomas removed surgically from around the carpus but the new tumour was associated with the flexor tendons and adequate surgery would have involved cutting many of the tendons, thus crippling the cat. Bleomycin was infiltrated into the tumour and surrounding structures and ECT was performed on tumour and margins. The cat, which had been slightly lame, was walking on the leg again after 3 days. Initially the skin was unaffected but, after 2.5 weeks it ulcerated and a necrotic mass sloughed out. Healing was rapid and the paw remained fully functional.

It will be several months before the full effect of the treatment can be evaluated as local recurrence is a common problem with fibrosarcomas

For further examples which may be more unpleasant to look at click here

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