Treatment of Canine Glioma with Convection-Enhanced Drug Delivery

Status –
Open

What is “convection-enhanced delivery” and how is it used in this study?

Non-surgical options for the treatment of cancer usually involve either radiation therapy or chemotherapy. Chemotherapy is simply the administration of a drug that has anti-cancer properties. The choice of which chemotherapeutic drug(s) to use is based upon a number of factors including: cancer type, tumor location, health of the patient, acceptable route of delivery, drug effectiveness, etc. For example, although a certain chemotherapy drug may be available as a pill (usually preferable for patient and owner), the drug may only reach effective levels if given by an intravenous (IV) injection. Traditionally when a drug is given (IV injection, oral pill, muscular injection, etc.) it must first reach the bloodstream and then be carried to the tumor in the blood to have its effect. In the context of brain tumors, the “blood-brain-barrier” is a natural blockade to drug delivery. This is a functional roadblock that prevents potentially harmful substances in the blood from crossing into the sensitive brain tissue. Unfortunately, it also blocks most chemotherapeutic agents from reaching the brain. In cancer therapy, this barrier can be overcome by direct delivery of the chemotherapy drug to the brain tumor. When drugs are injected using traditional catheters (hollow tubes for delivery of liquids), the force of the injection pushes the tumor cells out of the way and causes damage of normal brain tissue. The drug also tends to flow back away from the tumor when the catheter is withdrawn. Convection-enhanced delivery (CED) catheters are special tubes with many tiny holes along its length that allows for a slower, more even delivery of the drug, directly to the tumor cells, which may allow for more effective brain tumor treatment.

Which animals are eligible for enrollment in this study?

Any dog with a specific aggressive brain tumor called a glioma that is healthy enough to undergo the surgery for catheter placement and chemotherapy can be included in this study. The brain tumor is initially found by a CT scan or an MRI and may be tentatively diagnosed as a glioma. The tumor must then be verified as a glioma with a magnetic resonance imaging (MRI) or computed tomography (CT) guided brain biopsy before your dog can receive treatment.

How much does the treatment of the glioma of this treatment and diagnostics cost?

Once the brain tumor is diagnosed as a glioma, the ensuing treatments (up to and including the three month recheck) will be performed at no cost to the dog's owners up to a maximum of $12,700, which is the estimated financial value of the entire treatment protocol. In addition, the value of prolonging your pet's life and of contributing to the efforts to find a cure for brain cancer in both dogs and people is immeasurable.

How are animals being chosen to enroll in this study?

Dr. Liz Pluhar, a veterinary surgeon and Principal Investigator of this study, one of the veterinary oncologists, Dr. Mike Henson and Dr. Brian Husbands, or a veterinary neurologist, Dr. Alistair McVey will perform a thorough physical and neurological examination of your dog. Blood will be drawn for screening tests to make sure your dog is healthy enough to undergo the general anesthesia for surgical catheter placement and chemotherapy. A small amount of this blood will be stored for our glioma DNA bank. If an MRI has not already been done, your dog will be placed under general anesthesia under direct supervision of board-certified anesthesiologists and certified technicians for a brain MRI to determine the location, size, and imaging characteristics of the mass. If the tumor has an appearance consistent with that of a glioma, a piece of the tumor (biopsy) will be taken. A small sample of cerebrospinal fluid (CSF) will be collected for analysis after the MRI. Any dog that has a biopsy that confirms the brain tumor is a glioma can then be enrolled in the study.

What is the course of therapy for the dogs?

Dogs that are enrolled in this clinical study will help to establish the safety and effectiveness of a novel cancer treatment. This is an experimental treatment in dogs that has been shown to be very effective in killing large brain tumors that were artificially induced in rats' brains. If this therapy is effective in reducing or completely removing the tumor in dogs, it will continue to be offered as a treatment for other dogs with the tumor and will be offered as a treatment for people with this type of brain cancer.

To determine if convection-enhanced delivery has a significant effect in dogs with glioma, a clinical study will be conducted. Dogs enrolled in the study will receive high level of care: surgical biopsy of the tumor and surgical placement of a CED catheter to directly deliver chemotherapy to the brain. All dogs under anesthesia will be monitored and supervised by a board-certified veterinary anesthesiologist at the Veterinary Medical Center (VMC). The surgery will be performed by Dr. Pluhar, a board-certified veterinary surgeon at the VMC, and may be assisted by Dr. Stephen Haines, MD, neurosurgeon at the Fairview-University of Minnesota Medical Center. Prior to surgery, each dog will have a planning magnetic resonance imaging (MRI) study to determine the size and character of the tumor, and to plan the exact placement of the CED catheter. Another MRI will be performed post-operatively to assess the drug delivery. If this is deemed inadequate, the catheter will be repositioned and another MRI scan performed.

The dogs will be kept in the intensive care unit of the VMC with constant monitoring and care given by Dr. Pluhar and the ICU doctors and staff. Analgesia (pain relief) and management of any seizure activity will be given on an individual basis under the direction and supervision of the trained doctors and staff. When fully recovered, each dog will be released to their owners’ care.

There will be regular rechecks of the dog by Dr. Pluhar, Dr. Henson, Dr. Husbands, or Dr. McVey. Complete physical and neurological examinations and a quality of life assessment will be made 2 weeks after surgery. At 1 and 3 months after surgery, an MRI and routine blood work will be performed in each dog in addition to these tests.

The decision to euthanize your dog will ultimately rest with you; however you will be required to donate your pet’s remains so tissue samples can be obtained for further testing and research studies.

What are the risks to the patients?

There are several risks involved in this study. First, we do not know whether the convection-enhanced delivery of a chemotherapy drug will be effective at treating glioma in dogs. Although this is pilot study and this particular drug delivery system has not been used in dogs with glioma, it has greatly increased survival time when given to rodents with large gliomas without appreciable side effects. The chemotherapy chosen for this study (carboplatin) is a commonly used cancer drug in dogs, however, it has not previously been delivered in this fashion (i.e. directly to the brain tumor). A similar dose was administered by CED to rats with an experimentally induced glioma and they experienced no adverse symptoms.

General anesthesia, in and of itself, can be dangerous. Although it is rare, animals can have unexpected reactions to the anesthetic drugs. Tests will be run to minimize your dog's chance of having problems with anesthesia. Drugs that are most safe for dogs with brain masses and are reversible will be used and the anesthesiologists are always on hand in case of an emergency.

Although the surgery to place the catheter in the tumor is a major procedure, placement will be performed in a way that prevents causing more damage. State of the art preoperative planning and postoperative care will also be used to minimize the chance of complications.

If at any time during the study, if a patient is not doing well, Dr. Pluhar will perform an examination immediately. If necessary, the clinical symptoms will be managed medically and another MRI performed. The most common recurrence or worsening of symptoms is due to tumor growth. The decision to discontinue treatment and euthanize is always the owners.

How can I find out more?

If you or your veterinarian thinks that your pet could benefit from enrollment in this study, or if you would just like more information about gliomas or any of our studies, please contact Dr. Pluhar at 612-626-8387 (referral center), 612-625-1162 (office) or by email

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