HEALTH

By KATE NOBLE/LONDON

Elizabeth Clear, a 64-year-old housewife, had long been a 30-a-day smoker. But it still came as a shock when doctors running tests for a hiatus hernia at London's Whittington Hospital found something much more serious — lung cancer. And when consultant Siow Ming Lee proposed enrolling her in a trial using thalidomide to treat the disease, she got an even bigger shock. "That was the drug that damaged the children, wasn't it?" she asked. Despite her initial misgivings, she's now pleased she was given thalidomide — her cancer has been in remission for nearly a year.

Thalidomide has a fearsome reputation for causing more damage than it repairs. Scientists first synthesized the drug in Germany in 1954 as an antihistamine. As a way to control allergies it was not especially effective, but it did show promise as a medication for nausea, which is why it was given to pregnant women in the 1960s to curb morning sickness. But it also caused terrible deformities in their babies. By the time thalidomide was banned in 1962, it had been blamed for severe handicaps — severely misshapen limbs, organ defects — in more than 5,000 children. Today researchers are investigating the interactions that caused those deformities to discover whether the drug can be safely harnessed to provide a new weapon in the war against cancer.

A More Gentle Way Thalidomide works in three ways to fight cancer: it prevents the formation of new blood vessels that feed tumors, reduces inflammation and kick starts the body's immune system. While existing anticancer agents kill off lymphocytes and white blood cells, which control immune and inflammatory responses, thalidomide has no toxic effect on them. It is also a potent inhibitor of cell movement, thus preventing inflammation around a tumor. Though thalidomide does have side effects, like dizziness and tingling in the toes, it is more gentle than existing therapies.

After thalidomide's catastrophic debut, scientists found that the deformities occurred because the drug prevented the formation of new blood vessels. This, in turn, prevented normal fetal development. Now several British research groups are exploring how thalidomide can be used to stop blood vessels forming in and around tumors. Kill the formation of new vessels, they reason, and you kill the tumor.

Recent studies into thalidomide treatment of some of the most intractable cancers — lung and pancreatic cancer and multiple myeloma — show promising results. Thalidomide has "three exciting properties to home in on: it can inhibit tumors directly, activate the immune system and be anti-inflammatory," says Keith Dredge of St. George's Hospital Medical School in London, who's working with Revamid, a type of thalidomide, in patients with melanoma and pancreatic cancer. "Tumors seem to be able to hide from the immune system, preventing the body from fighting the invader itself," Dredge explains. So in addition to the drug's tumor-fighting properties, thalidomide's ability to activate the immune system is crucial to beat the disease.

At Guy's Hospital, also in London, Steven Schey has been treating 24 patients suffering from multiple myeloma with Actimid, another thalidomide analogue. Previous treatment regimens had been ineffective on these patients, but Schey found a 65% response rate to Actimid. He also noticed that the drug lessened the feelings of lethargy and nausea that afflict chemotherapy patients. And it helps them put on weight, which increases their feelings of wellness. "Even patients whose disease didn't respond to the drug still felt better," he says. It's still "early days" to claim too much for thalidomide, Schey warns, but he is setting up a full clinical trial with 350 patients. At University College Hospital, Lee's results with patients like Clear have shown enough promise for Cancer Research U.K. to fund a full clinical trial of thalidomide. "We are very cautious because we don't want to raise any false hopes," Lee says, "but certainly the results from the study were encouraging."

Cancer treatment is only one of thalidomide's promising uses. Since 1964 the drug has been the standard treatment for leprosy. Thalidomide does not kill the bacteria that cause leprosy, but it does change the body's immunological and inflammatory response to those bacteria — which is why researchers are investigating its potential uses in autoimmune disorders like HIV, Behçet's disease and Crohn's disease.

This time around researchers are taking stringent precautions against any possible embryo-damaging side effects. They insist that women of childbearing age use two forms of contraception and undergo pregnancy tests before starting thalidomide treatment, and that men also use contraception in case sperm might be affected. They advise too that the precautions continue for a month after the last treatment.

Even though more clinical trials and several years of research are needed before thalidomide could be approved for use, the drug's potential is real. What was once the most feared drug in the pharmaceutical armory could become one of its most valuable.

From the Jan. 26, 2003 issue of TIME Europe magazine