Peter, on front page of at least the early edition of today's NYTimes. Hope the mention of Folkman retains its magical stock price impact <G>.
Walter
November 18, 1999
Thalidomide Found to Slow a Bone Cancer
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By SHERYL GAY STOLBERG
ASHINGTON -- In a serendipitous discovery that grew out of the pleas of a New York woman whose young husband was dying of cancer, scientists will report Thursday that thalidomide, the notorious sedative that caused the deformation of thousands of babies in the 1960's, can slow the course of a deadly bone cancer. Some experts say it may become the most effective new drug for the disease in decades.
In a study of 84 patients with advanced forms of the disease, multiple myeloma, Dr. Bart Barlogie, an oncologist at the University of Arizona, and his colleagues found that one-third were helped by thalidomide, and two went into complete remission. While the numbers are not high, experts say the results are startling because the patients had not responded to other therapies and the disease is notoriously difficult to treat.
"This is very significant," said Dr. Philip Griepp, a myeloma expert at Mayo Clinic in Rochester, Minn. In an editorial in The New England Journal of Medicine, which is publishing Barlogie's findings Thursday, two experts at the Dana-Farber Cancer Institute in Boston wrote that, given the condition of the patients, "the effect of thalidomide is indeed remarkable."
Thalidomide was banned from pharmacy shelves worldwide in the early 1960s, after the birth of thousands of deformed babies, mostly in Europe, Canada and Japan, whose mothers took it for morning sickness. In recent years, it has been experiencing a revival, however, and scientists are studying it for everything from AIDS to breast cancer. Last year, the Food and Drug Administration approved it in the United States for the first time, for treatment of leprosy.
The drug is being marketed by Celgene Corp. of Warren, N.J., which provided the medicine for Barlogie's study and helped analyze the data, but did not otherwise contribute to the research. One of the 12 co-authors of the article is a Celgene employee and two others said they owned stock in the company.
Celgene spokesman Bruce Williams said Wednesday that the company intended seek approval to market the drug for myloma.
No one was investigating thalidomide for multiple myeloma until Barlogie was pushed into it by Beth Wolmer, a Manhattan lawyer whose husband, Ira, had received a diagnosis of multiple myeloma in 1995, at the age of 35. Dr. Ira Wolmer, a cardiologist, underwent three bone marrow transplants and tried an experimental vaccine, his wife said, but nothing worked.
"I was always looking for something new," said Mrs. Wolmer in a telephone interview Wednesday. "I would routinely call scientists in their labs to find out what they were working on." But they had nothing to offer.
One of them, however, told Mrs. Wolmer about Dr. Judah Folkman, a researcher at Harvard Medical School who has theorized that cancer may be treated by retarding angiogenesis, the growth of blood vessels that feed tumors. One of the substances under study in Folkman's laboratory was thalidomide.
A researcher there, Dr. Robert D'Amato, said Wednesday that he has been pursuing the idea that drugs that caused severe side effects, like birth defects, would also inhibit blood vessel growth. He said his experiments show that the drug inhibits tumors in rabbits and mice.
Folkman could not be reached Wednesday because he was traveling. He referred questions to D'Amato. But Mrs. Wolmer said that when she called him, late one Saturday night in his laboratory, and asked him if he thought thalidomide might work against multiple myeloma, "it was like a light bulb went off."
Mrs. Wolmer told Barlogie to call Folkman.
By the fall of 1997, Barlogie said, he had obtained permission to test thalidomide in Wolmer. The drug did not work for Wolmer; he died in March 1998. But when Barlogie tested it on a second patient, he said, the man "went into almost a complete remission."
Despite Folkman's theory about angiogenesis, the researchers who conducted the myeloma study are not certain precisely how thalidomide works against the disease. Inhibiting the growth of blood vessels is only one possibility; the drug may also work by stimulating the immune system's reaction against myeloma cells, or it might limit the growth of the cells, either directly or by restricting other factors in the bone marrow that enable them to grow.
The study measured the success of thalidomide by looking at the level of a certain protein produced by the cancer causing cells. In analyzing the patient's urine, they found that the protein levels were reduced by at least 90 percent in eight patients, including the two who went into remission.
The levels dropped at least 75 percent in six patients; at least 50 percent in seven patients; and at least 25 percent in six patients; in all, 32 percent of the 84 patients were helped.
Most of the patients experienced the known side effects of the sedative, including constipation, weakness, sleepiness and tingling or numbness in their extremities. But because the side effects are different from those of standard chemotherapy, experts said they were encouraged that thalidomide might be used in conjunction with other drugs to treat myeloma and offer relief to patients in earlier stages of the disease.
The American Cancer Society estimates that 13,700 people in the United States will be diagnosed with multiple myeloma this year; 11,400 patients with the disease will die. Griepp of the Mayo Clinic said the median survival time of those with the disease is three and a half years. Experts say new treatments are urgently needed; the five-year survival rate for patients treated with chemotherapy has remained unchanged, at 29 percent, for more than four decades.
Dr. Joseph Michaeli, a myeloma expert at Memorial Sloan-Kettering Cancer Center in New York, said it would be especially important for researchers to learn how thalidomide worked, particularly because some patients responded while others did not.
"It's a clue," Michaeli said. "Once we figure out why some patients show sensitivity to thalidomide while others do not, I think we will gain some valuable insight into the biology of myeloma." He said Barlogie's work provides "an important lesson," adding, "Here is someone who apparently had no rationale to use this drug on these particular patients, but he did go this extra mile, and he sort of hit the jackpot, in a way."
As for Mrs. Wolmer, she is credited at the end of the New England Journal for her persistence. "I didn't save the person I was doing this for," she said. "But I'm glad it helped everyone else."
Copyright 1999 The New York Times Company
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