Shift in thinking yields new cancer therapies Research is leading to varied approaches in fighting the disease


In yet another promising finding on the cancer front, researchers at the Johns Hopkins oncology center have found a drug that temporarily stops tumors in people who hadn't responded to any other treatment.

The small study, presented yesterday at the annual meeting of the American Society of Clinical Oncology, showed that of 27 patients with pancreatic, ovarian and other tumors, 14 had tumors that stopped growing for at least four months.

Of this group, five patients had tumors that didn't spread for seven to 11 months.

The news is the latest in a series of findings to emerge from the major meeting of cancer researchers in Los Angeles this week. They've announced that a drug can attack the genetic cause of breast cancer; that a medicine used to treat osteoporosis may prevent breast cancer; that Taxol, a standard drug for advanced breast cancer, also works if given in the disease's early stages.

Top researchers say they're witnessing a "bewildering" number of approaches to pursue against cancer.

But people are paying particular attention to compounds such as the one Hopkins tested, drugs that stop tumors by depriving them of blood. Boston researchers recently made the drugs famous by showing that two wiped out cancer in mice.

In Maryland, physicians are testing similar drugs in people. And so far, results are good.

Researchers at Hopkins and the University of Maryland Greenebaum Cancer Center are cautious and hopeful.

They think their work might help turn some of the fastest-growing and most deadly cancers into chronic illnesses.

It's all part of a significant shift in cancer research.

For the past quarter-century, most doctors focused on bombarding cancer cells with toxic drugs that often simultaneously harmed or killed the patient.

In the past several years, though, scientists have started taking advantage of new knowledge about how cancer is born and grows in the body. They're trying to turn off specific functions in cancer cells.

They're also beginning to look at the problem from the other side of the equation: how the human body responds and why it allows the disease to invade.

"It's a paradigm shift," said Dr. Ross Donehower, director of medical oncology at the Johns Hopkins Oncology Center.

"But I don't think that any of these are going to be the answer, that we can abandon the way things were done in the past. It's complementary and hopefully, synergistic."

Take, for example, the Hopkins study presented yesterday. While the drug didn't shrink the tumors, it seemed to hold them at bay.

"If you could make them just stop and not grow, that would be a fabulous development," said Dr. Louise Grochow, an associate professor of oncology who led the study.

She explained that a patient could have tumors in various organs, but 90 percent of an organ would have to fail before the person would notice symptoms.

This means that in the future, a cancer patient with a primary tumor might have that treated by standard therapies such as surgery, chemotherapy and radiation.

The places where the cancer had spread would be treated by taking pills like the ones Grochow tested, possibly for the rest of the patient's life. Since the drug is not toxic, like chemotherapy, there are few side effects.

The drug also appears to have the bonus of protecting bone.

In the case of one patient in the trial, a tumor wrapped around the young man's spine and devoured the bone marrow inside it. But somehow the cancer hadn't been able to do what it usually does: eat through the bone. Grochow and her colleagues realized that the reason must have been the drug, BAY 12-9566.

But there are many caveats.

For one, tumor growth is often not monitored before a study starts, so it's difficult to know whether the drug or some other factor is responsible for stopping growth, said Dr. Robert G. Fenton, associate professor at the UM Greenebaum Center.

Also, tumors in mice grow relatively fast compared with tumors in people, so it's unclear whether drugs that work in animal models will apply to people who deal with cancer over several years.

"Human cancer is a hundred different diseases," Fenton said. "It may be that these drugs will work in one but not the other."

Researchers around the country are trying to sort this out. The drugs are called anti-angiogenesis because they stop the growth of the skinny, kinky blood vessels that allow tumors to grow.

At the Greenebaum Center, scientists have been tracking one class of these drugs in people, and they believe the pills stop enzymes from breaking down cell walls and tissue to create space for the tumors to expand.

"They have great potential either by themselves or in combination with our currently existing therapies," said Dr. Barry Meisenberg, the center's deputy director.

"But the true significance is going to have to wait for the outcome of these clinical trials."

UM researchers have finished one of the final, advanced trials, known as phase 3, with a drug called Marimastat. This medicine blocks a broad spectrum of as many as 15 enzymes that try to grow more blood vessels for the tumors in pancreatic, ovarian, breast and gastric cancers. Results are due soon.

Both UM and Hopkins are enrolling patients now for these and other trials.

Pub Date: 5/20/98

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