Pegaspargase

Key Terms: Acute lymphocytic leukemia, Induction therapy.

Definition

Pegaspargase (also known as PEG-L-asparaginase and Oncaspar) is a medicine used to stop growth of cancer and formation of new cancer cells.

Purpose

Pegaspargase is used as part of induction regimen for the treatment of acute lymphocytic leukemia (ALL) in children who developed an allergy to asparaginase.

Description

Pegaspargase is a slightly changed version of the native form of asparaginase (E. coli asparaginase) that is linked to polyethylene glycol (PEG) molecule. This medicine was made available in 1994 under the brand name Oncaspar. It is more expensive than the native form and is mainly used in patients who developed an allergy to the native form. The advantage of pegaspargase over asparaginase is that it is less likely to cause an allergic reaction and has a longer duration in the body and can be given less frequently. Pegaspargase kills cancer cells by depleting a certain amino acid in the blood (L-asparagine), which is needed for survival and growth of tumor cells in patients with acute lymphocytic leukemia. Fortunately, normal cells can make their own Lasparagine and are not dependent on L-asparagine from the blood for survival.

Pegaspargase is mainly given in combination with other drugs vincristine (a vinca alkaloid anticancer drug) and steroids (either prednisone or dexamethasone). Other chemotherapy medicines are added to this regimen if a patient is at a high risk for disease recurrence.

Recommended Dosage

Adults and Children With Body Surface Area Greater Than 0.6 Square Meters

In induction chemotherapy for acute lymphocytic leukemia, doses vary between different chemotherapy protocols. The usual dose is 2500 international units (IU) per square meter of body surface area given every 14 days.

Children With Body Surface Area Less Than 0.6 Square Meters

In induction chemotherapy for acute lymphocytic leukemia, the usual dose is 82.5 IU per kg given every 14 days.

Administration

This medicine can be given directly into the muscle (intramuscular) or into the vein (intravenous). Intramuscular injection of pegaspargase is preferred over the intravenous route because of lower risk of liver disease, blood clotting problems, stomach, and kidney problems. When used intramuscularly, it must be administered as deep injection into a large muscle. When given intravenously, it must be infused over one to two hours. Patients will be monitored closely by a physician for 30 to 60 minutes.

Precautions

The use of this medication should be avoided in patients with active pancreatitis (inflammation of the pancreas) or history of pancreatitis and in patients who have had a serious allergic reaction to pegaspargase in the past.

Pegaspargase should only be administered in a hospital, and a patient will need to be observed by a physician for the first hour.

This medication can lower the body's ability to fight infections. Patients should avoid contact with any individuals that may have a cold, flu, or other infection.

Pegaspargase should be used with caution in the following populations:

• People with gout (it may increase uric acid levels and worsen gout).
• People with diabetes (it may increase blood sugar).
• Breast-feeding mothers (it is not known if asparaginase crosses into breast milk).
• Women who are pregnant or may become pregnant (unless benefits to the mother outweigh the risks to the baby).

Patients should contact a doctor immediately if any of these symptoms develop:

• fever, chills, sore throat
• chest pain or heart palpitations
• yellowing of the skin or eyes
• puffy face, skin rash, trouble breathing, joint pain
• drowsiness, confusion, hallucinations, convulsions
• unusual bleeding or bruising
• stomach pain with nausea and vomiting, and loss of appetite (anorexia)

A physician will be doing blood tests before starting therapy and during therapy to monitor complete blood count, blood sugar, pancreas, kidney, and liver functions.

Side Effects

Pegaspargase is a very potent medicine that can cause serious side effects. An allergic reaction with skin rash, itching, joint pain, puffy face, and difficulty breathing is a side effect that happens very quickly after the drug is injected. The allergic reaction to pegaspargase is less common than with asparaginase. The severe type of this allergic reaction (anaphylaxis) can result in death. Other common side effects include nausea, vomiting, diarrhea, loss of appetite, stomach cramps, yellowing of the eyes or skin, swelling of hands or feet, and pain at the injection site. Less frequent side effects include high blood sugar, chest pain, heart palpitations, headache, chills, night sweats, convulsions, decreased kidney function, increased blood clotting, mouth sores, and decreased body's ability to fight infections. Usually the side effects of pegaspargase are more severe in adults than in children.

Interactions

Pegaspargase can decrease effectiveness of methotrexate (an antimetabolite, or compound that prevents the synthesis and utilization of normal cellular metabolite, anticancer drug) in killing cancer cells when given right before and together with methotrexate. The use of these two medicines together should be avoided.

Pegaspargase can decrease breakdown and increase toxicity of cyclophosphamide (a DNA alkylating anticancer drug).

Risk of liver disease may be increased in patients getting both pegaspargase and mercaptopurine (a purine analog antimetabolite anticancer drug).

This medicine can increase blood sugar, especially when given with steroids.

Pegaspargase should be given after vincristine instead of before or with vincristine because it can increase the risk of numbing, tingling, and pain in hands and feet.

People taking blood thinners (warfarin, heparin, or its derivatives), aspirin, and non-steroidal anti-inflammatory drugs (ibuprofen, naproxen) may be at an increased risk of bleeding. A physician and a pharmacist must be informed about any prescription or over-the-counter medications the patient is taking.

—Olga Bessmertny, Pharm.D.