Brand Names: Elspar, Kidrolase, Laspar

Commercially available in Canada. Compounded (custom-made) injectable can be obtained.

Background

In order to make an effective medication for the treatment of cancer, some fundamental differences between normal cells and cancer cells must be defined. The chemotherapy agent must exploit this cellular difference so that normal cells are spared and only cancer cells are injured. L-asparaginase works by exploiting the unusually high requirement tumor cells have for the amino acid asparagine.

Chemical structure for the amino acid asparagine. Graphic Courtesy of MarVistaVet.com.

Asparagine is an amino acid required by cells to produce protein. Asparagine can either be produced within a cell or it can be absorbed into one from the outside (i.e., it is consumed in the patient’s diet, absorbed into the body, and made available to the body’s cells). Tumor cells, more specifically lymphatic tumor cells, require huge amounts of asparagine to keep up with their rapid, malignant growth. This means they use both asparagine from the diet as well as what they can make themselves (which is limited) to satisfy their large asparagine demand.

The enzyme L-Asparaginase destroys asparagine outside the cells, forcing the cells to rely completely on what they can produce on their own. Normal cells do not require nearly as much asparagine to survive and are able to make all the asparagine they need internally. Tumor cells, alternatively, become depleted rapidly and die if the dietary supply is cut off because they cannot manufacture enough internally to support their continuing growth.

How this Medication is Used

Mostly this medication is used against lymphoma, but it is also used in some mast cell tumor protocols. Unlike other chemotherapy agents, it may be given as an intramuscular or subcutaneous injection without fear of tissue irritation. This is not a medication that would be used at home.

Side Effects

Not all normal cells can rely on internally produced asparagine. The cells of the body that normally reproduce rapidly or engage in heavy protein synthesis for other purposes may be unable to grow or function normally in an environment depleted of asparagine. The cells in question are those of the intestine, bone marrow, liver, and pancreas. While bone marrow suppression is rare with this medication than with other chemotherapy agents, there is still some concern about blood clotting disorders, toxicity to the liver, diarrhea and/or vomiting, and the development of canine pancreatitis or feline pancreatitis. Fortunately, in most patients, it is well tolerated.

L-asparaginase is an enzyme produced by bacteria. It is inherently a foreign protein and as such, can produce an anaphylactic reaction. This is a rare complication, but pre-treatment with antihistamines or corticosteroids may be prudent in some cases. Anaphylactic reactions to L-asparaginase are much more common in dogs than in cats. 

L-asparaginase may interfere with blood clotting, may raise blood sugar levels, may raise liver enzyme blood tests, and may cause liver disease in some patients.

The most common side effect of this medication is vomiting.

Interactions With Other Drugs

Methotrexate is another common anti-tumor drug. L-asparaginase and methotrexate work against each other and should be given at least 48 hours apart.

Toxicity of vincristine, another chemotherapy agent, may be more likely if vincristine and L-asparaginase are given at the same time. It is common to separate them by a couple of days to avoid this issue.

Prednisolone tends to raise blood sugar levels to a greater extent when used in combination with L-asparaginase.

Concurrent use of L-asparaginase and non-steroidal anti-inflammatory medications can increase the risk of inappropriate bleeding.

Concerns and Cautions

When L-asparaginase destroys asparagine, ammonia is a by-product. In patients with compromised liver function, the transient high levels of ammonia in the blood could pose a toxic problem. Liver disease does not preclude the use of L-asparaginase but it is important to watch for symptoms referable to liver disease (generally neurologic abnormalities/hepatic encephalopathy).

The use of L-asparaginase has been associated with pancreatitis. It is best not used in patients with a history of pancreatitis.

In 2012, the only commercial manufacturer of Elspar® decided to discontinue production indefinitely for business reasons. It is possible for L-asparaginase to be obtained through compounding pharmacies.

Asparaginase is normally derived from E. coli bacteria. With the loss of the commercial product Elspar®, a product derived from Erwinia chrysanthemum (Erwinaze®) has been released. This product is not equivalent to Elspar.  It is best to use compounded asparaginase. The Canadian product Kidrolase is E. coli based.