joel m. eichen d.d.s.

Tissue culture and animal studies do not translate precisely into
human therapy! It may suggest an avenue of investigation but only
foolish people would yank out teeth based upon very thin science!

Joel

**********


That is because samples of cancer that scientists study in test tubes
or implant in mice are simpler than real cancerous tumors, with more
uniform properties, Fox Chase's Meropol said. Real cancers tend to
evolve various strategies for surviving and evading drugs.

***************

Posted on Tue, Jul. 08, 2003

Cancer drug shows promise despite scandal
By Faye Flam
Inquirer Staff Writer

The ImClone scandal may have ruined company chief Sam Waksal and
damaged stockholder Martha Stewart, but the intriguing cancer drug at
the root of it all, Erbitux, is emerging with its reputation intact.

The drug, whose initial government rejection led to securities-fraud
charges against Waksal and Stewart, has shown promising results
against colon cancer in its most recent study.

Erbitux is one of a handful of new drugs changing the direction of
cancer treatment, designed to attack malignant cells without harming
normal cells. Its reemergence may eventually eclipse the tawdry news
that has surrounded its maker.

"This case illustrates the hopes and dreams and frustrations with the
development of new treatments for cancer," said Louis Weiner, chairman
of medical oncology at Fox Chase Cancer Center in Philadelphia.

"When you strip away all the sleaziness," Weiner said, "what has been
learned about colon cancer is that in people whose cancers are no
longer responding to chemotherapy, the addition of Erbitux will cause
significant clinical improvement in 10 percent to 15 percent of
cases." Combining Erbitux with more chemotherapy produces improvement
in more than 20 percent of cases.

The drug has yet to be tested against people whose disease is less
advanced and who therefore stand a better chance of recovery.

Colon cancer kills about 53,000 Americans every year, second only to
lung cancer.

Erbitux and other "targeted" therapies aim to kill cancer cells while
sparing healthy ones. They tend to have much less severe side effects.

"There's been a great interest in the past decade in identifying
features of cancer cells that distinguish them from normal tissue,"
said Neal J. Meropol, director of the gastrointestinal-cancer program
at Fox Chase.

The idea that was to become Erbitux emerged around 1980 in the mind of
John Mendelsohn, who was doing cancer research at the University of
California, San Diego. At the time, a number of cancer researchers
were experimenting with the use of antibodies, proteins that the
body's immune system makes to fight disease. But most researchers were
looking at antibodies as a way to prompt a patient's immune system to
kill cancer cells.

A different course

Mendelsohn took a different tack. He was trying to find ways that
cancer cells differed from healthy ones - characteristics that could
be exploited or targeted with antibody-based drugs.

Mendelsohn, along with colleague Gordon Sato, was interested in the
various signals that prompt malignant cells to grow out of control. He
and others found that the cancers depend on a substance called
epidermal growth factor, or EGF.

A molecule of EGF is like the ignition key to a car, said Mendelsohn,
who is now president of M.D. Anderson Cancer Center in Houston. That
key fits into a lock - the EGF receptor - which sits on the surface of
cells, he said.

Once the keys go into the locks, "the cells get a signal to
proliferate," Mendelsohn said.

'Gum' in the lock

Ordinary cells also depend on EGF and EGF receptors, especially cells
in the skin, but cancer cells have 1,000 times the normal number of
EGF receptors, he said. That is one reason cancers tend to grow and
spread.

Mendelsohn reasoned that if he could interfere with this lock-and-key
system, he could stop cancers from growing. "How do you stop a key
from getting into a lock?" he asks. "You put chewing gum in the lock."

The chewing gum he created was the antibody that was to become
Erbitux.

Once the key gets into the lock, a number of other steps have to take
place to signal the cell to divide. Other drugs interfere with the
process at various points. Mendelsohn invented one such drug, called
Iressa, which is now approved for treatment of lung cancer.

Mendelsohn started testing Erbitux against cancer cells in a test tube
and tumors implanted in mice. It seemed to work, but so do many other
drugs that eventually fail.

The Food and Drug Administration reports that only 20 percent to 25
percent of cancer drugs that look promising in the lab end up working
well in real patients.

That is because samples of cancer that scientists study in test tubes
or implant in mice are simpler than real cancerous tumors, with more
uniform properties, Fox Chase's Meropol said. Real cancers tend to
evolve various strategies for surviving and evading drugs.

When it came time to test Erbitux in people, ImClone Systems Inc.
started with a group who had advanced colon cancer and who were not
responding to the standard chemotherapy drug, called irinotecan.

Those people were given a combination of Erbitux and irinotecan.
ImClone said that about 20 percent of them saw their tumors shrink.

Although the results suggested the drug could help many people with
cancer, the FDA rejected ImClone's application for approval.

The FDA questioned not the drug itself but the way ImClone set up the
trial.

When ImClone's CEO learned the drug would not be approved without
further testing, he unloaded stock in his own company and urged his
family to do the same. The government says Martha Stewart acted on a
tip from her stockbroker and sold her 3,928 shares, too, avoiding
losses of more than $45,000.

Waksal pleaded guilty to insider-trading charges and last month was
sentenced to seven years in prison. Stewart has pleaded not guilty to
charges that could mean jail time and stiff fines.

And yet, the drug was far from dead in scientific circles.

Two other targeted therapies have recently come on the market. One,
Gleevec, has led to some dramatic recoveries for people with a certain
type of leukemia known as CML. Another drug, Herceptin, seems to work
well for certain cases of breast cancer. Like Erbitux, both of these
drugs work by interfering with the way cells receive the signal to
divide.

Women with breast cancer can now get a test that predicts how well
they are likely to respond to Herceptin. Only 20 percent are
candidates and even then, the drug does not always work. Herceptin
saves lives, but it is far from a guaranteed cure.

Scientists say Erbitux will also work extremely well on about 10
percent of colon-cancer cases - but they do not yet have a test that
predicts who is in that 10 percent.

"One hundred percent of appropriately selected people will respond,"
said Fox Chase's Weiner. "How do we find out who they are?"

Soon after the 2001 scandal broke a German company, Merck (not related
to the U.S.-based Merck & Co.), conducted a similar trial to ImClone's
but used Erbitux alone, as well as in combination with existing
chemotherapy, as the FDA had suggested.

It did not cure anyone of advanced cancer, but in about 23 percent of
the patients, the combination shrank their tumors and made the
patients feel better. Erbitux alone shrank tumors for 11 percent of
patients.

Scientists announced these results last month at a meeting of the
American Society of Clinical Oncology.

It's not unusual for a new drug to create such a roller-coaster ride,
Weiner said. "There have been instances of enormous hope, even hype,
for these agents, followed by the puncturing of the balloon when they
don't yield the results everyone had hoped for," he said. Erbitux is
not a cure for cancer. "But in the end, you're ahead of where you
started."

"My fervent hope is that FDA won't hold a grudge against ImClone and
place unnecessary obstacles for what looks like a valuable addition to
our treatment arsenal," he said.


--------------------------------------------------------------------------------
Contact staff writer Faye Flam at 215-854-4977 or
fflam@phillynews.com.


--
Joel M. Eichen, D.D.S.
Philadelphia PA

http://www.phillyducks.com
We’re Just A Duck Call Away!


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meaning no one IN PENNSYLVANIA
has seen the tooth or teeth in
question so take this advice in
proper context ~ its the internet!

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