This is from the L.A. Times:
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Friday, April 27, 2001
Key Breast Cancer Study Was a Fraud
By THOMAS H. MAUGH II, ROSIE MESTEL, Times Medical Writers
A key study pointing to the effectiveness of high-dose
chemotherapy and bone marrow transplants in treating metastatic breast
cancer was based on faked data, cancer experts said Thursday.
The American Society of Clinical Oncology announced that an
unscrupulous South African researcher, Dr. Werner Bezwoda, has led
thousands of women with breast cancer to undergo expensive,
debilitating and often fatal bone marrow transplants. His data were
fraudulent, suggesting the controversial procedure was more effective
than it actually is, the society concluded.
"Bezwoda . . . duped us all," Dr. Larry Norton, the organization's
president-elect, said at a news conference.
The new revelations do not mean that bone marrow transplants are
worthless, the oncology society said, only that they have not yet been
proven effective. Several large clinical trials are underway to
determine precisely how beneficial they are, and the society reiterated
its position that women should undergo the procedure only if they are
enrolled in a clinical trial.
The oncology society also urged insurance companies to help pay
for ongoing clinical trials, but concluded that the companies had no
responsibility to pay for bone marrow transplants performed outside
those trials.
Bezwoda was fired from his post at the University of Witwatersrand
in Johannesburg in 1999 after revelations that he had faked data in a
preliminary report of another study on the use of high-dose
chemotherapy and bone marrow transplants in patients where the
malignancy had spread to lymph nodes.
On Thursday, the oncology society said that an audit of a 1995
paper by Bezwoda showed that it also was fraudulent and took the
unprecedented step of withdrawing it.
A specially convened team of experts sent to Johannesburg to audit
his 1995 research concluded that there was no scientific basis for
Bezwoda's very positive findings.
The 1995 study had concluded that women with metastatic breast
cancer who received high-dose chemotherapy followed by a bone marrow
transplant had a 95% response rate, compared to only 53% among women
who received conventional treatment. That finding was a linchpin in the
ensuing wave of support for the treatment, Norton said, and helped
entice many women into undergoing the treatment.
"This is a stunning betrayal of public trust," said Dr. Lawrence
H. Einhorn, the oncology society's president.
At least 30,000 American women have undergone the procedure at an average cost of about $100,000. In the initial studies, at least, 10% to 20% of the women died as a direct result of the treatment. It has been used less commonly, however, since the initial reports of the fraud that led to Bezwoda's firing.
Insurance companies' responsibility to pay for bone marrow
transplants has been a great source of controversy and litigation.
Several women have received large jury awards because their insurers
would not pay. And as many as 10 states have mandated that companies
pay for the procedure.
The companies, in turn, have said that the procedure is
experimental and that its reputed benefits have not been proved. The
oncology society's statement seemingly validates that position.
The American Cancer Society agrees. "There is no clear proof that
high-dose chemotherapy followed by a bone marrow transplant gives a
sufficiently improved outcome to warrant insurance companies'
reimbursing for it," said Dr. Harmon Eyre, the cancer society's medical
director.
Interest in high-dose chemotherapy was already strong when Bezwoda
published his 1995 paper. The idea was to use very high doses of
anti-cancer drugs to kill breast cancer cells. These doses also kill
bone marrow, however, so the patient's immune system must be rescued
with a bone marrow transplant.
Bezwoda's report, however, was purportedly the first randomized
trial to test the effectiveness of the therapy and find a benefit.
"Although it was a trial of only 90 patients, its influence was
greatly magnified by the intense debate ongoing in the United States
about the value of high-dose chemotherapy for breast cancer," the
oncology society's report said.
After the scandal about Bezwoda's 1999 report, the University of
Witwatersrand invited a team led by Dr. Raymond B. Weiss of Georgetown
University to examine Bezwoda's records. It uncovered "substantial
evidence" of scientific misconduct.
Among its findings:
* The study protocol--or plan--was written nine years after the
study actually began.
* There were at least three treatment-related deaths among those
receiving high-dose chemotherapy, although the 1995 report said there
were none.
* There were no records at all for 29 of the 90 patients.
* There were insufficient records for many other patients, and
some women were treated with drugs and regimens not consistent with the
published information.
* There were untrue statements in eight other publications by
Bezwoda.
"It's really a terrible story," said Dr. Stephen Forman, of the
City of Hope National Medical Center in Duarte. "You trust physicians
to do the right thing, and this was obviously an example where--for
reasons only he knows--he not only misled other physicians but, more
importantly, misled a lot of women."
Forman and Dr. John Glaspy of UCLA's Jonsson Comprehensive Cancer
Center agree that the appropriate place for women getting high-dose
chemotherapy for their breast cancer is, for now, in clinical trials.
But what do you do, asks Glaspy, when a patient with a cancer that is
likely to kill her wants treatment--but does not want to take part in a
clinical trial?
That question haunts physicians on the front lines. "It's always a
little easier for the generals behind the battlefield with the map to
say 'go left,' or 'go right,' " he said. "It's a different issue for
the guys with the rifles in the trenches."
The report and associated material are available at the oncology
society's Web site: http://www.asco.org.
Copyright 2001 Los Angeles Times
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