Studies Refute Marrow Procedure for Breast Cancer
After nearly a year of controversy and negative findings capped Friday by the firing of a South African researcher, physicians are reluctantly concluding that bone marrow transplants have no role in treating most cases of breast cancer.
About 30,000 women have been treated with the procedure at a cost of more than $3 billion. But the overwhelming consensus is that the procedure--at least as it is now performed--offers little or no benefit to women with the often fatal disease.
The one ray of hope had been offered by Dr. Werner Bezwoda of the University of Witwatersrand in Johannesburg, South Africa. Bezwoda had reported success last May at a U.S. cancer meeting.
But at the same meeting, five groups reported on breast cancer clinical trials and four found no benefit from transplants. And last week, the New England Journal of Medicine released a formal report from one of those trials indicating that the technique provided no benefit for women with metastatic breast cancer.
Now, a U.S. team that went to Johannesburg to study Bezwoda’s results reported Friday on the Web site of the journal Lancet that he had doctored his results as well as committing a number of other egregious errors in his research.
Although many physicians believe transplants could still be useful in some cases, the transplants should definitely “not be done as a part of routine care,” said Dr. Harmon Eyre, medical director of the American Cancer Assn.
“It’s time to return to the drawing board” and look at other approaches to treating breast cancer, Dr. Jonas Bergh of the Karolinska Institutet said in an editorial also released by Lancet.
Among those approaches are newer cancer drugs that don’t have the toxicities associated with existing treatments; agents that block the tumor’s blood supply; biological agents, such as Herceptin, that target the specific biochemistry of breast tumors; lasers that are used to destroy tumor tissue; and vaccines that stimulate the body’s own immune system to attack the tumors.
“Those are the things we are most excited about,” said Nancy Braun, president of the Susan G. Komen Breast Cancer Foundation.
Still, not everyone is ready to write off the transplants.
“I really don’t know any more in the year 2000 than I did in 1997” about the utility of the transplants, said Dr. John Glaspy of UCLA’s Jonsson Comprehensive Cancer Center. He believes that ongoing trials will show some benefit from the procedure for women who have been brought into remission by chemotherapy and whose cancer has not metastasized--spread to other organs.
Dr. James Doroshow of City of Hope Medical Center concurred that “there is very little controversy that what has been published to date shows a benefit in this group.”
But that group represents fewer than 10% of all breast cancer patents, and most existing studies have not been able to include enough women in this group to reach definitive conclusions.
The subject of all this controversy is not a cancer treatment, but rather a technique to offset the potentially lethal effects of very high doses of chemotherapy for various types of cancer. Early researchers reasoned that if traditional doses of anti-cancer drugs could kill many cancer cells, higher doses could kill more.
Unfortunately, those higher doses also kill bone marrow cells, making the drugs lethal. Physicians circumvented that problem by removing bone marrow cells from the patient before chemotherapy, then infusing the cells afterward to restore the immune system.
The treatment is effective for certain types of cancer, such as selected leukemias and lymphomas, and researchers hoped it would work for breast cancer as well. Early results suggested that it did, prompting a great demand for the procedure.
But there proved to be a downside that was costly in a number of ways. The transplants run to $100,000 or more, and insurance companies balked at paying. Moreover, the procedure killed 10% to 20% of the first women treated.
Spurred by several high-profile lawsuits against insurance companies, 10 states now require companies to pay for the procedure. The federal government also requires that insurers of its employees pay for the procedure, but does not cover the cost in the Medicare program.
But since the negative results reported at last May’s meeting, said Glaspy, “the teeter-totter [of perceptions] has swung back in the opposite direction.”
Only Bezwoda reported success at the meeting, and other researchers expressed doubt about his findings. On Friday, their doubts were confirmed when U.S. researchers said Bezwoda had not used the drugs he claimed to have used, did not follow his own protocol for the study, did not have an appropriate control group of women, did not obtain informed consent from his patients and did not even have approval from his university’s human ethics committee to conduct the study.
But even before these newest revelations, attitudes were changing. Last month, Aetna, the nation’s largest insurer, said it would no longer pay for the bone marrow transplants for breast cancer unless the women were enrolled in clinical trials.
Kaiser Permanente still covers the procedure, but “the number of referrals [seeking it] has diminished greatly since May,” said Dr. Neil Kogut. “Patients are aware of these trials and results. Physicians are aware of them. There’s much less enthusiasm.”
When he does suggest a bone marrow transplant, added Dr. Derek Raghovan of USC’s Norris Comprehensive Cancer Center, “People get all tense and feel that you are heading them in a bad direction.”
That attitude is typified by Fran Visco, president of the National Breast Cancer Coalition. “How can anybody look at these data and think this is something that we should continue doing?” she asks.
But bone marrow transplants are not a moot issue, Raghovan added. “I think we’ve actually come to a more realistic expectation for it.” The procedure is not for everybody, but for a very small number of women, it might be useful, he said.
In another 18 months, experts noted, the major U.S. study of the technique will have progressed far enough to perhaps provide some definitive information.
In the meantime, concluded the cancer society’s Eyre, “the most heartening thing that has come out of this is that insurance companies have agreed to pay for clinical trials of breast cancer treatments.” That should open the door for a much greater amount of progress.
The report of the U.S. team that investigated Bezwoda’s study is on the Web at www.thelancet.com. The university’s response is at www.wits.ac.za. Other analyses are available at www.nci.nih.gov and www.cancer.org.
