Thalidomide, a drug that caused ghastly birth defects a generation ago but has been resurrected in recent years as a promising cancer treatment, failed in a study to prolong the lives of patients with multiple myeloma.
Other studies have found thalidomide helped myeloma patients both early on and when given after they relapsed or didn't respond to standard treatments.
But a large study done by researchers at University of Arkansas for Medical Sciences found that in newly diagnosed multiple myeloma patients given thalidomide on top of an already-grueling chemotherapy regimen, the thalidomide eventually stopped working, and those patients rapidly declined and died.
About 65 percent of the patients were still alive after five years _ no better than the rate in those who got the other treatments only. The thalidomide also had punishing side effects.
``It's a puzzle,'' said lead researcher Dr. Bart Barlogie, director of the university's Myeloma Institute for Research and Therapy and a major proponent of thalidomide for treating cancer. Multiple myeloma includes a half-dozen types of cancers of the bone marrow, the body's blood-making factory.
The study was reported in Thursday's New England Journal of Medicine. It was paid for by Celgene Corp., maker of the Thalomid brand of thalidomide, and the National Cancer Institute.
Thalidomide was once used for morning sickness and insomnia in 48 countries but was never approved in the United States. It was banned worldwide in 1962 after 12,000 babies had been born with missing or flipper-like limbs, facial deformities and defective organs.
Celgene's Thalomid has U.S. approval for treating leprosy complications, but doctors are free to prescribe it for cancer and other diseases. However, women can take it only if they sign an agreement to use both barrier and hormonal contraception because one pill early in pregnancy can kill or severely harm a fetus.
In the study, 668 patients underwent a grueling regimen of chemotherapy involving seven rounds of multiple cancer drugs, plus two transplantations of their own bone marrow stem cells, instead of the usual one transplantation. Half the patients also took thalidomide daily throughout months of chemotherapy and subsequent years of maintenance therapy.
In both groups, the treatments killed 8 percent of patients each year.
Initially, the thalidomide group fared better, with cancer cells dropping to undetectable levels _ what is called ``complete response'' _ in 62 percent of patients, compared with 43 percent in the other group. But that early advantage evaporated as the patients stopped responding to thalidomide; they then died much more quickly, making average survival the same for both groups.
The thalidomide group also had higher rates of serious side effects, including dangerous blood clots, bowel obstructions, fainting because of abnormal heart rhythms, low levels of infection-fighting white blood cells, and tremors and tingling. About 30 percent of patients on thalidomide stopped taking it within two years; more than 60 percent stopped within four years.
``You're not going to be able to put that many patients through this regimen'' because it is so intense, said Dr. Mecide Gharibo, a multiple-myeloma specialist at the Cancer Institute of New Jersey.
Barlogie said the intensive regimen boosted median survival for both groups of patients. It is now at seven years and could hit nine, he said. That is far better than the three or four years previously common for patients with the disease, for which there was little or no effective treatment just a decade ago.
Dr. Morton Coleman, director of the Center for Lymphoma and Myeloma at Cornell University, said he still thinks thalidomide is valuable, based on other research.
``The final jury is still out on the thalidomide story,'' Coleman said.
The study also was important in showing that complete response does not always predict long-term survival, Drs. Michele Cavo and Michele Baccarani of the University of Bologna wrote in an accompanying editorial. Researchers and doctors have long considered complete response early in treatment to be a sign of success.