Thalidomide: New uses for notorious drug

For many, the word "thalidomide" conjures up tragic images of babies born with shortened or missing arms and legs. Between 1957 and the early 1960s, thalidomide was used by several thousand pregnant women across the world to ease their morning sickness. But many who took the drug in the early stages of pregnancy gave birth to babies with severe birth defects.

Now, decades later, thalidomide isn't used for morning sickness. But it has received approval from the Food and Drug Administration (FDA) to treat one skin condition and a type of cancer, and it's being investigated as a treatment for many other disorders.

Thalidomide's return isn't without controversy, though. Children born to mothers who took thalidomide fear that allowing people to take the drug could mean more babies will be born with severe disabilities.

If you're considering thalidomide as a treatment option, follow your doctor's directions exactly. Weigh the benefits and risks of the drug to help you decide whether thalidomide is right for you.

New uses for thalidomide investigated

Despite its withdrawal from the market, thalidomide research continued.

In the mid-1960s, scientists determined that thalidomide was an effective treatment for erythema nodosum leprosum, skin lesions caused by leprosy. The FDA approved thalidomide (Thalomid) for this use in 1998.

In May 2006, the FDA approved thalidomide, in conjunction with dexamethasone, for the treatment of multiple myeloma — a cancer of the plasma cells. This treatment is only for newly diagnosed multiple myeloma. Thalidomide appears to slow the growth of myeloma cells and prevent them from attaching to bone marrow cells.

In conducting their research on thalidomide, doctors have found that the drug has properties that may prove useful in treating other diseases and conditions. Though it isn't clear exactly how thalidomide works, it appears that the drug:

• Reduces inflammation. Thalidomide reduces the production of tumor necrosis factor-alpha (TNF-alpha) — a cell protein that can cause inflammation. People with inflammatory conditions such as arthritis and Crohn's disease have high levels of TNF-alpha in their bodies.
• Prevents formation of new blood vessels. Angiogenesis is the medical term for the formation of new blood vessels. Tumors need nourishment from blood vessels to grow and spread. If thalidomide prevents the formation of blood vessels to the tumors, it could stop the growth and spread of some cancers.

Target areas: Inflammatory conditions, HIV and cancer

Researchers continue to investigate thalidomide for use in other diseases and conditions. Though more study is needed to evaluate the risks and benefits of the drug, thalidomide has shown promise in three main areas.

Inflammatory diseases
Researchers hope thalidomide's ability to reduce inflammation by regulating the immune system will further advances in treating several inflammatory diseases, including:

• Skin conditions. Certain inflammatory diseases can affect your skin, causing rashes and lesions. Thalidomide has shown promise in treating skin conditions associated with sarcoidosis, lupus and Behcet's syndrome.
• Arthritis. When used in combination with other drugs, thalidomide may help control the inflammation associated with rheumatoid arthritis. Thalidomide may also play a role in treating arthritis-related conditions, such as ankylosing spondylitis, Still's disease and Sjogren's syndrome.
• Inflammatory bowel disease (Crohn's disease). When combined with other medications, thalidomide may control signs and symptoms of Crohn's disease, a disease that causes inflammation in the digestive tract.

HIV
HIV — the virus that causes AIDS — can weaken your immune system, increasing your risk of certain complications. Thalidomide is sometimes used to treat HIV-related mouth and throat ulcers. Although this use hasn't been approved by the FDA, doctors can prescribe thalidomide for other indications (off-label use). This was the case with thalidomide and multiple myeloma until its approval by the FDA in 2006. Preliminary research shows thalidomide might also help treat Kaposi's sarcoma, a cancer of the blood vessel walls mostly found in people with HIV, as well as weight loss and body wasting.

Cancer
It isn't clear how thalidomide works in treating cancer. But preliminary clinical studies have found that thalidomide, when combined with other drugs, may show some promise in treating several types of cancers, including:

• Multiple myeloma
• Kidney (renal cell) cancer
• Brain tumors
• Melanoma
• Myelofibrosis

Thalidomide may also play a roll in improving quality of life for people with advanced cancers. It may improve appetite and cause weight gain, though more study is needed.

Special procedures required to prevent pregnancy

If you and your doctor decide thalidomide is the right treatment for you, you will need to agree to the terms of a restricted distribution program required by the FDA to prevent birth defects. As part of this program, you will:

• Receive a packet of patient education materials
• Sign a consent form
• Use two forms of contraception if you're a woman
• Use a condom if you're a man

If you suspect you're pregnant, stop taking thalidomide and contact your doctor immediately. Remember: No method of birth control is completely reliable except for avoiding sexual intercourse.

Side effects other than birth defects

People taking thalidomide might also experience other side effects. The most serious is peripheral neuropathy, a type of nerve damage. Less serious side effects include.

• Drowsiness
• Rash
• Dizziness
• Constipation
• Headache
• Nausea
• Dry mouth

Creating a safer thalidomide

Drugs that work like thalidomide but have fewer side effects may one day be available. Researchers are working on thalidomide analogs — drugs chemically similar to thalidomide. Lenalidomide is one such analog. This agent was approved for myelodysplastic syndrome (with 5q- syndrome) in January 2006. Like thalidomide, it appears active in multiple myeloma, although it has not yet been approved for this indication. Clinical trials are examining the safety and efficacy of these analogs.

Until a safer version is available, talk to your doctor if you have concerns about thalidomide. Understanding thalidomide's history, its risks and its potential benefits can help you decide if it's right for you.

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