Thalidomide Shows Pre-Leukemia Promise

MONDAY, Aug. 13, 2001 (HealthDayNews) -- Thalidomide, the drug blamed for horrific birth defects when it was used for morning sickness in the 1960s, may slow the progression of a rare form of pre-leukemia, new research suggests.

This latest study adds another illness to the growing list of diseases the once-maligned drug seems to help.

Although not approved by the U.S. Food and Drug Administration for general sale in the United States, thalidomide is already considered a good treatment for leprosy and a deadly form of blood cancer known as multiple myeloma. Geraldine Ferraro, who ran for vice president on the Democratic ticket in 1984, testified recently before a Senate subcommittee on its success in slowing her myeloma. However, experts have warned the potent drug may cause serious blood clots if used with certain chemotherapy treatments.

In the latest research, done at Rush-Presbyterian-St. Luke's Medical Center in Chicago, 20 percent of the patients with myelodysplastic syndrome, often a forerunner to acute leukemia, responded well to thalidomide treatments. The findings are in the Aug. 15 issue of Blood.

"Here is the second disease in the last couple of years where thalidomide is useful," says Dr. Azra Raza, lead author and director of the Myelodysplastic Syndrome Center at Rush-Presbyterian. "The real significance of this study is that, yes, this is the right strategy to pursue. It [thalidomide] is proving to be a very exciting drug."

However, she cautions, it's too soon to tell whether thalidomide can actually stop the disease in its tracks.

Raza believes thalidomide works because it blocks the formation of the blood vessels needed to make tumors grow, and it suppresses the production of proteins called cytokines. Those proteins play a role in causing bone marrow cells, which make blood cells, to commit suicide. With the syndrome, the bone marrow makes too many blood cells that then die off for no apparent reason. In response, the body's immune system goes into overdrive.

"A lot of noise is being made by the immune system," Raza says. "The bone marrow looks like a war zone. Thalidomide calms down the immune system."

Celgene Corp., which makes one type of thalidomide, collaborated on the study and provided free medication for the patients. Raza also holds a financial interest in the New Jersey company. The National Cancer Institute and several other groups funded the study.

"We're very excited about this," says Jerome Zeldis, chief medical officer for Celgene. He adds the company has started a larger, multi-center trial of the drug's effectiveness with myelodysplastic syndrome. "It highlights the fact that there's another hematological problem, which might respond to thalidomide treatment."

Dr. Vincent Rajkumar, a hematologist at the Mayo Clinic, has been researching thalidomide's effect on multiple myeloma, a cancer of the body's plasma cells. He says people with this syndrome now have reason to hope.

"I think the drug is really promising for myelodysplastic syndrome," he says. "The drug does seem to raise blood counts for patients with the syndrome. The end point is not just improvement of blood counts, but whether the patient is prevented from getting leukemia."

Rajkumar notes that doctors have had trouble understanding the drug because it breaks down so quickly in the body. "It's tough to say, anti-cancerwise, why it works," he says.

But in the studies of multiple myeloma and myelodysplastic syndrome patients, those on thalidomide do have increased blood counts with few side effects, which include mild nerve damage and constipation, he says.

In Raza's study, 83 patients each started receiving 100 milligrams of thalidomide daily, and the dosage was gradually increased to 400 milligrams a day. Within the space of 12 weeks, 32 patients dropped out because of adverse reactions to the medicine.

Of the 51 patients who were left, 16 showed improvement, with increased platelets and a decreased dependence on blood transfusions. Significantly, 10 patients who had depended on blood transfusions no longer needed them.

That's important, Zeldis says, because transfusions cause medical problems of their own. Constant transfusions overload the body with iron, which can damage the liver and pancreas and cause diabetes. There's also a risk of infectious disease with a steady diet of transfusions, he adds.

Zeldis acknowledges the trial was small, and no placebo group was used. That's why the company set the larger trial in motion, he explains.

"To prove the point, we need to do a placebo-controlled trial," he says.

Thalidomide still spells disaster for unborn children, so any woman taking thalidomide is told to abstain from sex or use birth control at all times.

However, the syndrome in this latest study primarily affects people age 60 and older. And the drug is showing promise in other areas, as well, with early studies showing it helps stem weight loss in HIV patients. Its anti-inflammatory properties are also showing up in preliminary trials involving arthritis, ulcerative colitis, Crohn's disease, colon cancer and even congestive heart failure, Zeldis says.

Raza notes the very reason thalidomide caused birth defects in some children may be why it seems to work so well with some cancers. The drug inserts itself between the particular parts of DNA that happen to be linked to angiogenesis, or the formation of blood vessels. That could have stunted the development of limbs in embryos, she explains. But with cancer, you want to stop new vessels from forming since they feed tumors.

With cancer treatment, you take it one step at a time, she notes, adding, "This is one significant step showing us the way."

What To Do

Read what the U.S. Food and Drug Administration has to say about thalidomide.

The National Cancer Institute has this information on myelodysplastic syndrome. And here's more on the syndrome.