Interleukin-2 for Metastatic Melanoma

Interleukin-2 (IL-2) for metastatic melanoma is one of a few treatment options approved for the disease. Melanoma that has spread beyond the skin to distant organs is called "metastatic" (or stage IV) melanoma. The treatment options for metastatic melanoma have expanded dramatically in the last five to eight years, and some people do survive this most serious stage of the disease. If your oncologist has recommended IL-2, this overview will provide you with the critical information you need to understand how it works, its effectiveness and its side effects.

Interleukin-2

Also called Proleukin and aldesleukin, IL-2 was approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic melanoma in 1998.

IL-2 is different than a chemotherapy drug; it is actually a natural part of your body's immune system. It is a type of messenger molecule called a cytokine that is secreted from certain cells to alert other cells about an infectious invader. At least 15 different kinds of interleukins have been discovered since the 1970s: IL-2 is known to specifically stimulate the growth and maturation of two kinds of white blood cells, called T and B lymphocytes. The IL-2 used to treat metastatic melanoma doesn't come from the body but rather is mass produced, using the techniques of genetic engineering. It has the same properties as the natural version, but it has a slightly different name, aldesleukin.

Evidence for the Effectiveness of Interleukin-2

In the studies that led to approval, 6% of selected patients (those in good physical and mental condition) with metastatic melanoma had a complete response to high-dose IL-2, and 10% had a partial response. A complete response is defined the disappearance of all evidence of the disease. Responses were observed in patients with a variety of metastases, including in the lung, liver, lymph nodes, soft tissue, adrenal glands and subcutaneous (deep) layers of the skin. IL-2, however, is not recommended for patients with existing brain metastases.

Many clinical trials have been conducted (and are still being conducted) in an attempt to increase the response rates of IL-2 by combining it with other medicines. For example, a study demonstrated higher response rates when IL-2 was given in combination with a vaccine (22%) compared to IL-2 alone (13%). Unfortunately, many attempts to combine IL-2 with various chemotherapy drugs (cisplatin, vinblastine, dacarbazine and others)—an approach called "biochemotherapy"—as well as with other drugs (interferon-alfa2b, etc), have thus far shown no significant improvement in the statistic that really counts: survival time.

Use of Interleukin-2

IL-2 is given by a 15-minute IV infusion every eight hours for five days. Each treatment course consists of two five-day treatment cycles separated by a nine-day rest period, and multiple courses are the norm. You will typically be imaged about a month after finishing your first treatment. If you are responding, you'll likely be offered a second course of treatment for six to 12 weeks after finishing the first course. To be eligible for IL-2 treatment, you must be in relatively good physical condition, with good heart, lung, liver, and kidney function.

Potential Side Effects

IL-2 has frequent, often serious and sometimes fatal side effects. It should be given in a hospital under the supervision of a qualified healthcare provider experienced in the use of anticancer agents. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available. The rate of drug-related deaths in clinical trials of metastatic melanoma patients who received IL-2 was 2%.

Many of the side effects are due to "capillary leak," which begins immediately after treatment is started. Capillary leak results in the leakage of fluid and proteins out of blood that then causes a decrease in blood pressure. The most common side effects are as follows:

• Nausea, vomiting, diarrhea, loss of appetite
• Weakness and fatigue
• Flu-like symptoms (fever, chills, headache and muscle aches)
• Low blood pressure
• General pain, chest pain (angina)
• Breathing problems due to fluid in the lungs
• Weight gain, fluid retention
• Mental effects (paranoia, hallucinations, insomnia)
• Itching, peeling skin
• Anemia (low red blood cell count)
• Low platelet count (increasing the risk of bleeding)
• Low white blood cell count
• Kidney damage
• Mouth sores

These side effects are rarer but have been reported in some people taking IL-2:

• Abnormal heart rhythm, heart attack
• Respiratory failure
• Severe infections
• Gastrointestinal bleeding
• Thyroid problems
• Liver problems
• Severe dizziness, fainting

Cautions/Interactions

IL-2 can make the side effects of other drugs and diseases much worse, so tell your healthcare provider if you have:

• Kidney problems
• Heart disease
• Liver disease
• Lung disease
• A seizure disorder
• Thyroid disorder
• Infections
• Any allergies
• Any immune disorders

Also let your healthcare provider know about any over-the-counter or prescription medications you use, especially corticosteroids, blood pressure drugs, antidepressants, anti-anxiety drugs or other anticancer medications. Do not start or stop any medicine without healthcare provider approval.

Note: This information may not cover all possible precautions, interactions or adverse effects for this drug. If you have any questions about any drug you are taking, be sure to check with your healthcare professional.