aldesleukin

Aldesleukin is an interleukin injection drug prescribed to treat wide-spread cancer of the kidney and skin (melanoma).

Aldesleukin is a man-made protein that has the same action as native human interleukin-2 (IL-2) that is used for treating cancer of the kidney and skin. Interleukins are the messengers by which white blood cells communicate with each other to coordinate inflammation and immunity. Among its actions, IL-2 increases the number and activities of certain types of white blood cells called lymphocytes, monocytes, and macrophages that are involved in inflammation and immunity.

For example, lymphocytes fight viral infections, regulate the immune system, and fight cancers. The exact mechanism by which aldesleukin fights tumors is unknown. Aldesleukin in given only by injection. Aldesleukin was FDA approved in May 1992.

Aldesleukin causes side effects in almost every organ. Because of these side effects, aldesleukin only can be given to patients who are physically and mentally able to tolerate them. Most of the side effects are due to "capillary leak" which begins immediately after treatment is started. Capillary leak results in the leakage of proteins out of blood. This causes a loss of fluid from the blood, a decrease in the volume of blood, and a decrease in blood pressure. The decrease in blood pressure can be dramatic and even result in death. More than two-thirds of patients require injectable medications to treat the low blood pressure.

Other important side effects are:

• wheezing,
• abnormal heart rhythms,
• heart attacks,
• drowsiness,
• paranoia,
• sleep disturbances,
• headache,
• fatigue,
• weakness,
• malaise,
• loss of appetite,
• visual changes,
• alterations or loss of taste sensation,
• hypothyroidism (low thyroid hormone),
• anemia,
• low platelet count,
• itching,
• rash,
• nausea,
• vomiting,
• diarrhea,
• abdominal pain,
• constipation,
• abnormal liver tests, and
• jaundice.

The recommended dose is 600,000 IU/kg intravenously over 15 minutes every 8 hours for 14 doses followed by 9 days of rest then another 14 doses.

Use of aldesleukin with drugs that share similar toxicity and side effects results in shared side effects that are more severe. For example, drugs that cause damage to the heart, for example, doxorubicin (Adriamycin), can worsen the toxic effects of aldesleukin on the heart. Similarly, drugs that damage the kidneys such as aminoglycosides (Garamycin, Nebcin, Amikin) or nonsteroidal anti-inflammatory drugs, for example, ibuprofen (Motrin, Advil) can worsen the toxic effects of aldesleukin on the kidneys. Aldesleukin also affects the nervous system; therefore, combining it with narcotics, sedatives, or tranquilizers may add to its effects on the nervous system. Finally, drugs that cause liver damage such as isoniazid (INH) increase the toxic effects of aldesleukin on the liver.

Aldesleukin stimulates the immune system. Corticosteroids (for example, methylprednisolone [Medrol] or prednisone) inhibit the immune system. Therefore, aldesleukin and corticosteroids will have opposing effects if used together. Use of such combinations, in fact, may decrease the anti-tumor effect of aldesleukin. Nevertheless, when aldesleukin is used, clinicians may use dexamethasone (a very powerful corticosteroid) to decrease side effects of aldesleukin such as dyspnea, confusion, fever, nephrotoxicity, or hepatotoxicity, despite the possible decrease in benefit.

Beta-blockers (for example, propranolol [Inderal, InnoPran]) and other antihypertensive drugs may increase the blood pressure reducing effect of aldesleukin. Individuals treated with interleukin-2 drugs may develop late reactions (fever, chills, nausea, vomiting, rash, hypotension, edema, and renal failure) to iodinated contrast media used for some X-rays. These reactions may occur when contrast media is administered 4 weeks to several months after receiving interleukin-2 drugs.

It is not known whether aldesleukin can cause harm to the fetus. Because of its known side effects, the manufacturer recommends that it only be given to pregnant women using extreme caution.

It is not known whether aldesleukin is excreted in breast milk. Because of its known side effects, the manufacturer recommends that it only be given to breastfeeding women using extreme caution.

What preparations of aldesleukin are available?

Vials containing 22 million IU (international units) of aldesleukin as a lyophilized (freeze-dried) powder, with diluent.

How should I keep aldesleukin stored?

The vials should be stored in a refrigerator at 2 C to 8 C (36 F to 46 F ) before and after reconstitution with diluent. The vials should not be frozen. The solution should be brought to room temperature prior to infusion and used within 48 hours of reconstitution. Since the vials do not contain a preservative, any unused portion must be discarded.

Other problems associated with capillary leak include congestion in the lungs, difficulty breathing (which can occur in one-half of patients), wheezing, respiratory failure (1 out of every 11 patients), and swelling due to fluid accumulation in various tissues in the body (half of all patients). Abnormal heart rhythms occur in 1 out of every 12 patients, and heart attacks in 1 out of every 50. Bleeding from the stomach, intestines, and kidney or liver damage also can occur. Moreover, between two-thirds and three-fourths of all patients receiving aldesleukin develop kidney damage. Most of the side effects caused by capillary leak begin to resolve a few hours after stopping aldesleukin therapy.

Three-fourths of all patients receiving aldesleukin have mental changes including paranoia and hallucinations. Drowsiness, sleep disturbances, headache, fatigue, weakness, malaise, loss of appetite, visual changes, and alterations or loss of taste sensation also occur.

Between 20% and 50% of patients develop hypothyroidism (low thyroid hormone) which usually requires replacement with thyroid drugs, for example, levothyroxine (Synthroid; Levoxyl). Anemia occurs in 3 out of every 4 patients and may necessitate blood transfusions. A low platelet count (increasing the risk of bleeding) occurs in two-thirds of patients, and low white blood cell count in one-third. Infection may occur in one-quarter of treated patients and possibly lead to death. Itching occurs in half of all patients and rash in one-quarter. Occasionally, rashes can be severe. Generalized pain occurs in one-half of all patients. Gastrointestinal side effects occur frequently. Nausea or vomiting occur in 7 out of every 8 patients, diarrhea in 3 out of every 4, ulcerations of the mouth in 1 out of every 3, and abdominal pain or constipation in less than 1 out of every 10. Liver tests become abnormal in 3 out of every 5 persons who receives aldesleukin and jaundice in 1 out of every 9.