The drug thalidomide, which was banned in the United States after it caused serious birth defects in 10,000 babies worldwide four decades ago, can produce dramatic improvements in people with a cancer of the bone marrow, according to a study being published today.The study is a “significant advance” in treatment for myeloma, Dr. Kenneth Anderson, a myeloma specialist at Boston’s Dana-Farber Cancer Institute, said yesterday. Myeloma, a cancer that arises in the bone marrow and that crowds out normal tissue so that the marrow can no longer make healthy blood cells, is diagnosed in almost 14,000 Americans a year. It is “notoriously difficult” to treat, Anderson said in an editorial accompanying the report in the New England Journal of Medicine. Typically, only 29 percent of people diagnosed with it survive for five years, despite treatment.
The new study, done at the University of Arkansas for Medical Sciences, involved 84 patients who had relapsed despite aggressive treatment, including marrow transplants and high-dose chemotherapy.
When given thalidomide in doses of up to 800 milligrams a day, 32 percent of patients improved at least somewhat, as gauged by lower levels of a myeloma-related protein in blood or urine tests. Two patients had complete remissions, meaning that their cancer was undetectable.
One year after starting treatment, about 22 percent of patients were alive without relapse; a total of 58 percent were alive, although some had progression of cancer. It is not clear how long the responses had lasted, although in some cases, the responses appeared to be “durable,” Anderson and his co-author, Dr. Noopur Raje, said in the editorial.
The lead researcher, Dr. Seema Singhal, formerly in Arkansas and now codirector of the myeloma and lymphoma program at the South Carolina Cancer Center at the University of South Carolina, said in a telephone interview that “the results are extremely encouraging.”
She added: “You kind of like to believe in magic, and once in a while it happens.”
Magic might be a description of thalidomide, because, at least in myeloma, scientists are less sure now about how it might work than they were when the study began.
Initially, Singhal and her colleagues decided to try thalidomide because it is an angiogenesis inhibitor, meaning it can block the chemical signals that trigger formation of blood vessels around tumors.
But in this study, many patients who responded to thalidomide did not show a reduction in the density of blood vessels that nourish tumors in the bone marrow. That could merely be a sampling problem: Every time a doctor conducts a biopsy on a small piece of bone marrow to study, there is a chance that the section sampled has more, or fewer, cancer cells and blood vessels than the rest of the marrow.
On the other hand, said Anderson of Dana-Farber, it may also be that thalidomide is acting in other ways. For instance, it may directly attack myeloma cells, or the so-called stromal cells of the marrow on which they grow. It might work by keeping myeloma cells from attaching to stroma cells. It might block chemical signals that help myeloma cells grow. Or it might nudge T-cells to attack myeloma cells.
The fact that thalidomide not only seems to work in advanced myeloma but that it also may have several ways of acting is part of the excitement, Anderson said.
After it was banned by the Food and Drug Administration in the 1960s because it caused birth defects in the babies of pregnant women, who took it for morning sickness, thalidomide was approved last year for a type of leprosy.
But the drug, made by Celgene, was approved with severe restrictions, including the stipulation that every person, male or female, who uses it must be enrolled in a government-monitored registry.
In addition, only doctors who have received training may prescribe it. Because it can cause birth defects, women must undergo pregnancy tests before using the drug, and both men and women must agree to use contraception.
In general, however, once a drug is approved for one use, it may legally be prescribed for others as well. In addition to its promise in myeloma, thalidomide is also being studied as a treatment for AIDS-related ulcers and a virulent type of brain tumor called a glioblastoma.