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In November of 1999, a specialty panel convened in Baltimore, Maryland to recommend for or against Medicare coverage of ‘human tumor assay systems’. In one and one-half days of intensive testimony, a single cancer patient addressed the panel, along with several practicing physicians who rely on the assays to guide their patients’ chemotherapy. Other experts presented research and opinions about the technology, but it is the real-world experience of doctors and patients that makes for rare and riveting reading in the abbreviated excerpts below. For the sake of brevity and clarity, minor editorial liberties have been taken with the transcript of that meeting.
Randy Stein, pancreatic cancer patient
Mr.
Stein was diagnosed in January 1997 with stage four
non-operable pancreatic cancer that had metastasized
to his spleen and kidneys. He sought and received an
assay on his tumor from the Weisenthal Cancer Group,
and found a doctor willing to prescribe the drugs that
test recommended.
“We went to the most famous
and most prestigious facilities available. We were
told go fishing if that’s what you like. We
were told, I don’t know why you’re still
alive. We were kept waiting by one of the grand gurus
of cancer for over an hour, told yep, it’s pancreatic
cancer, you have three months to live, and I have
to leave; I’m late for a root canal appointment.
We discussed sensitivity testing with each and every
one of them and their collective reactions were all
the same. They were against it. Their reasoning was
simple: the test tube doesn’t exactly duplicate
conditions in the body, and the testing may prejudice
the doctor’s chemotherapy choices. These same
doctors were also sure I would be dead two and a half
years ago.
After much deliberation, we decided
that although testing in the test tube may be different
than the human body, it did give us a better idea
of what the tumor was resistant to and what might
work. And let me tell you, when you have three months
to live, that sounds a lot better than just guessing
what chemotherapy to use.”
The current FDA-approved treatment
for pancreatic cancer with metastases is Gemzar, and
had I treated within the FDA guideline, I would be
dead.
All of this is why I am standing
here today, cancer free and begging you to approve
this type of testing.”
Richard Nalick, M.D., gynecologic
oncologist at the University of Southern California
School of Medicine; private-practice oncologist in Los
Angeles
To demonstrate his support for the technology, Dr. Nalick
presented a case history of one ovarian cancer patient
who came to him with a dense history of treatment including
a hysterectomy, the standard platinum-Taxol chemotherapy,
and high-dose chemotherapy with bone-marrow transplant
for $200,000. “Still her disease recurred,”
Nalick testified. He opened her abdomen, saw inoperable
disease, and sent a specimen of her tumor for an assay.
“The assay showed resistance
to every single drug of 27, except Gemcitabine and
platinum. She’s now totally free of disease,
off chemotherapy for a year and a half, and she’s
still working full time as an oncology nurse.
I feel just like Shakespeare said
in Hamlet: ‘Diseases desperate grown are by
desperate appliance relieved, or not at all.’
So my aggressiveness is based on extensive radical
surgery and then treating the patient with the drugs
that have been found on the assay to be the ideal
combination. I will continue to do that until I quit
practice.”
William Grace, M.D., private-practice
oncologist in New York City; formerly chief of cancer
research and chief of medical oncology at St. Vincent’s
Hospital
“I have an enormous conflict
of interest, because Larry Weisenthal (director of
the Weisenthal Cancer Group) makes me look good.”
I could have paraded in here a
roomful of patients with stories such as we’ve
heard today. I am a strong believer in this technology,
and it’s amazing.
I know many of my colleagues,
who don’t believe in this technology, essentially
chemo patients to death with one…combination
after another, not using this (assay) but just going
from one ASCO Journal to another ASCO abstract to
another. If you could predict that these patients
would not respond, you’d save patients a lot
of grief and a lot of money.
I have become now a guru,
along with Howard Bruckner in New York, for pancreatic
cancer, and we are all using Larry’s stuff to
tell us what combinations to use, and we’re
doing some exciting work in pancreatic cancer. You
just will not believe the results when you finally
see them.”
David Alberts, M.D., professor
of medicine, pharmacology, and public health at the
University of Arizona; associate dean for research in
the College of Medicine; chair of the Gynecologic Cancer
Committee for the Southwest Oncology Group
“There are 22 drugs that
are FDA approved for ovarian cancer and it is absolute
chaos, certainly in the second-line treatment of these
patients, to determine what drug should be used. I
can assure you that physicians are not infallible
in this situation. On the other hand, I think what
you’ve heard today is that the tests that we
have available to us can lead us out of the wilderness.
There is acceptable quality control and reproducibility,
acceptable accuracy, and acceptable clinical utility
of these tests, and this has been shown over and over
and over again, for a variety of tumor types.
If you’re sitting in your
office and you have specific information on the tumor
of the patient that shows that nine out of ten drugs
in the second-line treatment are associated with extreme
drug resistance, and one is associated with sensitivity,
and you’re going to see that patient in five
minutes, would you choose to look at that data, would
you be interested in that data, or would you like
to avoid that data?
I think Mr. Stein very eloquently
pointed out that if patients were given the opportunity
to really understand what the options were, there
is no question that they would want to be treated
according to the best knowledge that existed for them
on the basis of their tumor.
Cancer is still primarily incurable
but many new agents are available with activity. Their
selection must be, not just should be, guided by data,
not gut feelings. And unfortunately in oncology today
– and I think you’re all aware of it –
gut feelings are too pervasive in our selection of
treatment. These tests should be covered.”
Following a day and a half of testimony and thoughtful, sometimes poignant discussion,
eight members of the Laboratory and Diagnostic Services
Panel supported the technology, voting that sufficient
scientific evidence existed to demonstrate its clinical
utility in selecting appropriate chemotherapy for cancer
patients. On that critical motion, one panel member
disagreed and two abstained. The panel also attached
a list of concerns reflecting frustration that the deliberation
process and the available evidence – which threw
into one basket two markedly different types of assays
along with a wide variety of disease states, patients
and drugs – were insufficient for recommending
specific guidelines to practicing physicians.
Three weeks later, a Medicare executive committee took
up the panel’s report and voted 8 to 4 against
ratifying it. Essentially, the committee postponed action,
pending establishment of a more “consistent process
for panel review and assessment of the evidence.”
In March of 2000, the labs seeking a national coverage
decision withdrew their requests. Since then, the technology has received only one exhaustive and unbiased review by a regulatory body, conducted in 2006 by the northern California Medicare carrier. They voted to reimburse cancer patients for the tests.
If you’re interested in learning more about the
technology Marnie Schulenburg calls ‘ex vivo’
in her novel, you can find current information about
the test and the science behind it on the websites of
the following three labs. Two are U.S. labs; the third is in the United Kingdom. They all use the type
of cell-death assay (as opposed to cell proliferation)
described in the book, which is a critical distinction:
In 2004, the American Society of Clinical Oncology (ASCO) published an article recommending against use of ex vivo assays outside of clinical trials. Although ASCO is not a regulatory body and individual physicians are free to order the assays as they would any other medical test, insurers and oncologists are influenced by ASCO and the article stimulated more debate. Here are three informative links, two in support of the assays and one reporting on the controversy:
- COFIT response (Clinical Oncologists for Individualized Treatment)
- Letter to the editor of the Journal of Clinical Oncology from Dr. Michael Castro, 'Resisting a Fundamentalist Policy'
- Annie Appleseed 'reprint' of a Tara Parker-Pope article in the Wall Street Journal
For a balanced presentation of viewpoints surrounding
this technology, read this older but still valid article entitled
‘Pretesting
Tumors’ written by biologist and science
writer Evelyn Strauss, Ph.D. (For copyright reasons,
it will appear without two photos published with the
original article in Scientific American
magazine).
Anyone wishing to pursue further independent research should be forewarned that this laboratory test has been
tagged with a confusion of names over the years. The following list is no doubt incomplete:
- Chemosensitivity test / assay
- Human Tumor Assay Systems
- Cell Culture Drug Resistance Testing, or CCDRT
- DiSC assay
- TRAC assay
- EVA assay
- TCR assay
- Drug resistance assay, or chemoresistance assay
- Chemosensitivity and Resistance Assays, or CSRAs
- In vitro chemoresponse
- In vitro chemosensitivity
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