Cancer drug given new life

[Cary]

This seems promising, but still a few years away. I am hoping that the human trials will be restarted soon.

From the Harvard Gazette 2/26/04:

http://www.news.harvard.edu/gazette/200 ... 1-tnp.html

Cancer drug given new life

Its toxic side effects eliminated

By William J. Cromie

Harvard News Office

The cancer drug's effectiveness surprised everyone. Called TNP-470, it stunted the

growth of every malignancy it touched - animal tumors, human tumors, and

spreading tumors. It suppressed tumors of the ovaries, colon, prostate, and breasts.

In some cases the tumors shrank; in others, they disappeared.

But it was too good to last. Some patients whose malignancies were repressed, even

eliminated, started showing unacceptable side effects - problems with motor

coordination, seizures, and malaise.

TNP-470 was developed by Donald Ingber and Judah Folkman of Harvard Medical

School, two of the best in the business of cancer research. Folkman, Andrus Professor

of Pediatric Surgery and professor of cell biology, had discovered that cancers could

be starved to death by cutting off the growth of blood vessels they depend on for

nutrition. In his laboratory at Children's Hospital in Boston, he and his colleagues

produced several drugs that stifled the growth of such vessels. TNP-470 seemed to

be the most effective.

"It's a wonderful drug," Folkman comments. "It inhibits growth of the largest variety of

different tumor types of any drug yet tested. It works on metastatic (spreading)

tumors. It's rare that a drug does that."

So the side effects were a crushing setback. Folkman discussed the problem with

Ronit Satchi-Fainaro, a young chemist he recently hired as a research fellow. "I can fix

the problem," she told him.

Satchi-Fainaro realized that TNP-470 molecules are too small. They slip easily into

leaky new blood vessels growing into tumors; that's what made the molecules so

effective. But they also penetrate healthy cells. The researchers found them in the

spinal fluids of test animals. Their assault on nervous tissue was interfering with

motor coordination and producing seizures. Her solution: bulk up the molecules;

make them too big to get into any place but the tumor blood vessels.

It sounded too simple. But, Folkman admits, "Ronit knew more chemistry than I did.

That's why I hired her." He told her to go ahead.

A big surprise

The idea worked. The jumbo drug technically known as the new conjugated TNP-470,

slows the growth of deadly skin cancer (melanoma) and lung tumors in mice. Unlike

free TNP-470, it's too big to have toxic effects on the nervous system. The motor

coordination of the mice is fine and they develop normally.

Satchi-Fainaro, Folkman, and their colleagues describe the success in the March issue

of Nature Medicine. While waiting for publication of the report, the team tried jumbo

TNP-470 in other cancers, including spreading lung tumors in mice. It works well.

"Frankly, it was a big surprise; we didn't expect the results to be so good," Folkman

says.

"The conjugated drug molecules are too big to seep from normal blood vessels,"

Satchi-Fainaro explains. But they easily dribble out of leaky new blood vessels and

into the tumors. "Once inside the tumors, the copolymer [added baggage] is cleaved

chemically, and the TNP-470 can do its work. It stays longer in the tumor than the

free molecule, so it's more effective."

Will they now try jumbo 470 in humans? "Absolutely," Folkman answers quickly.

"Those who did the human trials with the free TNP-470 are eager to try the

conjugated drug." These include cancer researchers at Dana-Farber Cancer Institute in

Boston, a Harvard teaching hospital two blocks from Folkman's lab, and the M.D.

Anderson Cancer Center in Houston.

That doesn't mean that it will soon be available to patients. "We have to start the

testing all over again," Folkman points out. First there will be safety tests, then

efficacy tests; small groups of patients, then larger groups. "It'll be several years

before we can get FDA (Food and Drug Administration) approval." He says that's

"frustrating," but he has his game face on.

Folkman sees jumbo TNP-470 being used together with other drugs. One example is

Avastin, another blood-vessel wrecker based on his research that was approved Feb.

26 by the FDA. At Dana-Farber Cancer Institute, Avastin, combined with

chemotherapy, is being tested on runaway breast cancer. Chemical therapy has tough

side effects, so doctors give patients a chance to rest between doses. But blood

vessels grow back during such intervals, making it more difficult to stop the

spreading cancer. Now they use Avastin every day to choke and starve tumor cells.

Folkman pushes across the table a list of 17 different human tumors that respond to

free TNP-470. Another list shows that the drug halts the spreading of five different

lung and liver cancers. "That's amazing," he comments. "We expect the conjugated

drug will perform better in these and other cancers."

[Carleen]

This sounds so promising. I pray to God that this is as effective and as good as it sounds, and that it comes to human patients SOON!!!

[MO_Sugar]

This sounds like what so many of us need right now! I wonder if we as a group, can apply, lol.

God Bless,

MO

[karen335]

Cary,

Thanks for sharing. This sounds very promising. Let's pray that the FDA will approve it for quickly and maybe a cure or at least control for chronic illness. It sounds like maybe this is very promising for us...

Blessings & prayers,

Karen

[Cary]

Karen,

It's good to see you back and posting again.

Cary

[Melinda]

Cary--

Thank you for posting this! We will certainly keep both our fingers crossed and out eyes peeled for any updates on this.

Melinda

[cathy]

It sounds so promising, I dont understand why they cant hurry things up..If I am not mistaken I think Iressa received an accelerated FDA approval, I am not sure if that is the right technical term or not..

[Margaret]

Thanks so much for posting the article. I love that there is so much new stuff going on that it is difficult to stay on top of it all. How lucky we are to have each other.

Margaret

[Cary]

Cathy,

Here is an article explaining why we can't get the drugs sooner. The article is quite long, it deals with her mother's fight with lung cancer, but well worth the read. It seems that while we want drugs to be approved faster, there are other people that don't. Here is an excerpt.

http://tinyurl.com/32cl7

His idea, presented to the FDA last January, was to encourage companies to sell promising, unproven drugs to terminally ill patients who cannot get into clinical trials. This, he thought, would create a stronger incentive for companies to make the drugs available.

But the FDA rejected the proposal, known as "Tier 1 Initial Approval," citing concerns about giving its blessing too early in the process of showing a drug's benefit or safety. Burroughs and his group filed a citizens petition, then a lawsuit. "You've got to be a little bold," says Burroughs. "People's lives are at stake."

The FDA would not comment on the suit, but Richard Pazdur, head of the agency's oncology division, points out that the FDA seldom stands in the way when companies opt to supply drugs on a compassionate basis -- through individual requests or expanded-access programs. Several mechanisms exist for doing this. "In general, I think that what exists is sufficient," he says.

Perhaps surprisingly, the strongest objections have come from other cancer-patient organizations. Several widely regarded leaders, including Fran Visco, president of the politically influential National Breast Cancer Coalition, say the idea would create false hope and lead many patients to abandon scientifically based clinical trials that help test and refine new drugs.

Cary