Vioxx Makes Radiation More Effective; Angiogenesis and Gene therapy

[Guest guest]

Two stories from NHL-low list:

Popular Arthritis Drug May Enhance Radiation Effects

Against Cancer

ATTENTION: Medical editors

PHILADELPHIA, Nov. 7 (AScribe News) -- Researchers at

Jefferson

Medical College have shown in the laboratory that a

popular arthritis

drug, Vioxx, may enhance the effects of radiation

against cancer.

Interest in such arthritis drugs, known as cox-2

inhibitors and which

include the well known drug Celebrex, stems from the

mechanism by

which they apparently work against cancerous tumors.

According to

Adam Dicker, M.D., Ph.D., assistant professor of

radiation oncology

at Jefferson Medical College of Jefferson

University in

Philadelphia and a member of Jefferson's Kimmel Cancer

Center, who

led the work, the drugs appear to affect angiogenesis,

a process by

which a tumor's growth is fed by the development of

blood vessels. A

new field of research on anti-cancer drugs known as

angiogenesis

inhibitors has sprung up in recent years based on the

concept that by

blocking the formation of blood vessels, cancers

cannot grow or

spread without a blood supply to feed them.

Dr. Dicker presents his team's findings November 7 at

the American

Society for Therapeutic Radiology and Oncology meeting

in San

Francisco. According to Dr. Dicker, tumors actually

make cox-2, an

enzyme, and nearly every tumor " overexpresses, " or

makes too much of

it. It is also present in blood vessels associated

with the tumor,

though the enzyme's precise role is uncertain.

In animal models, both Vioxx and Celebrex have shown

anti-tumor

properties, in some cases even shrinking tumors,

possibly through an

anti-angiogenic effect. Other researchers have

demonstrated in animal

models that Celebrex enhances the effects of radiation

on tumors. But

little had been known, Dr. Dicker explains, about the

effects of

Vioxx. Dr. Dicker, using various laboratory tests and

a number of

different models for angiogenesis, showed the drug

also enhances the

effects of radiation on tumor cells by interfering

with angiogenesis.

" People are excited about cox-2 inhibitors because

they appear to

lower toxicity for patients with arthritis, " he says.

" In addition,

they also enhance radiotherapy effects and have

anti-angiogenic

activity. " Angiogenesis has become one of the hottest

areas of cancer

research. Some researchers believe that

anti-angiogenesis drugs will

expand the armamentarium of drugs that will halt

cancer growth, with

the disease becoming more a chronic illness patients

can live with.

Dr. Dicker is leading a number of clinical trials

looking at the use

of these inhibitors for the treatment of cancer. At

the same time, he

chairs the -2 Inhibitor Working Group at the

Radiation Therapy

Oncology Group, a federally funded cancer clinical

trials

organization that is conducting trials nationwide on

the use of cox-2

and its role in cancer therapy.

" There will be a lot of research in this area - it's

an exciting

time, " Dr. Dicker says.

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http://www.chicagotribune.com/news/nationworld/chi-

0111070348nov07.story?coll=chi%2Dnewsnationworld%2Dhed

Cancer treatment raises early hopes

Combined therapy uses X-rays to stir tumor-killing

gene

By Gorner

Tribune science reporter

Published November 7, 2001

Cancer researchers on Tuesday reported promising, but

very

preliminary, results from clinical trials of a novel

high-tech

therapy invented at the University of Chicago that

provides powerful,

precisely targeted treatments for tumors generally

considered

hopeless.

The results announced Tuesday at a convention of

cancer specialists

meeting in San Francisco may herald the birth of a new

anti-cancer

strategy, one that marshals a number of weapons at

once. The

procedure brings gene therapy, angiogenesis inhibitors

and radiation

therapy to bear on localized tumors.

It also could make lower doses of radiation more

effective, which

would benefit the estimated 60 percent of all cancer

patients who

undergo radiation each year in the U.S.

In the new therapy, doctors inject into tumors a

modified flu virus

carrying the supercharged gene for a potent immune

system protein

called tumor necrosis factor. TNF is a central

regulator of the

inflammatory response, crucial to wound healing, but

so powerful that

the body summons it only with great care, disarming it

quickly when

its job is done.

Once inside the tumor, the TNF gene sits quietly like

a Trojan horse

until the cancer is zapped by radiation. The X-ray

beam causes the

gene to switch on and start churning out high doses of

TNF, which

kills the tumor cells by destroying their blood

supply.

Seven advanced cancer patients at three institutions,

all of whom had

failed standard treatment and were due to receive

radiation therapy,

volunteered for the experiment. All had solid tumors

accessible for

repeated injections. They were to receive five

escalating doses of

the virus to determine safety levels.

Even though the tumors were large and the first dose

was minimal, all

the patients immediately responded, some dramatically.

In two of the seven, the tumors being tested simply

disappeared. In

two other patients, they shrank drastically. In the

remaining

patients, the cancer was held in check--it stopped

growing.

Experts said that such a response--seven out of

seven--is extremely

rare in Phase 1 cancer trials, which are not designed

to determine

the effectiveness of new drugs, only whether they are

toxic to

patients.

But even to the U. of C. researchers, who have been

working to

perfect the treatment for 10 years, the initial

results came as a

surprise.

" Certainly, this is very early data with just a few

patients, but the

important thing is the concept: You can control gene

therapy with

radiation, " said Dr. Ralph Weichselbaum, the U. of

C.'s chairman of

radiology and cellular oncology who invented the

combined therapy.

" Potentially, it could convert radiation to a systemic

treatment--

using X-rays to turn on cancer-killing genes wherever

they find tumor

cells. "

The synergistic technique so far has been shown to

cause tumor

regression in laryngeal, prostate, glioma, esophageal

and colorectal

cancers. The new data include cancers of the breast,

pancreas and

lung. But in principle, it could work for any solid

tumor,

Weichselbaum said, and those constitute 85 percent of

all cancers.

The first human trials of the combined therapy were

good news to

cancer pioneers.

" Ralph Weichselbaum is outstanding, a visionary

thinker in cancer

biology and radiation therapy, " said Harvard

University researcher

Dr. Judah Folkman, who for 30 years has developed his

theory of anti-

angiogenesis that has led to the creation of

tumor-starving drugs.

" I find these results very encouraging, " Folkman said.

" It's highly

unusual to see this kind of efficacy in a Phase 1

trial. And it's a

very elegant way to do anti-angiogenic therapy. "

To gene therapy pioneer Dr. French ,

of the

University of Southern California, " This is the first

example of a

true gene-therapy vector for cancer therapy. The idea

makes sense. It

has the right feel to it. And it will be a tremendous

advance in the

field. "

Preliminary results were reported Tuesday at the

annual meeting of

the American Society of Therapeutic Radiology and

Oncology in San

Francisco by physicians from the University of

Kentucky, Albert

Einstein College of Medicine in New York and U.S.

Oncology in Dallas.

Since 1999, Weichselbaum has worked with GenVec, a

biotech company in

Gaithersburg, Md. GenVec spokesmen said they will

begin at least one

major randomized Phase 2 study as early as next year.

In another trial under way at the University of

Chicago, 18 to 30

patients with soft tissue sarcomas, a rare but

dangerous cancer, will

undergo the TNF-radiotherapy treatment.

They will receive two injections during the first week

and one for

each of the next four weeks. Radiation therapy aimed

at the injected

tumor will begin the first week and continue for up to

five weeks.

The first patient, Goldberg, 50, of Chicago,

has seen the

tumor on his right knee shrink dramatically after five

weeks of

therapy. He reports no side effects, beyond the

discomfort of the

first injections.

" They used a bigger needle the first time and that

hurt, " he

said. " Since then they shifted to a smaller-gauge

needle and now I

barely feel a thing. "

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