Long, Hard Fight Still Seen Before Cancer Is Conquered : Health: Survival rates are up only 4.1% since the mid-1970s. And the incidence of the disease is on the rise.

Colleen Casey fingers a patchwork quilt stitched by her daughter Susan before the young mother of three died last spring.

Casey, 65, a retired La Mirada nurse, is not naive to the cruelty of illness. Her mother died of breast cancer. In 1966, at age 40, Casey underwent a bilateral mastectomy for breast cancer. She had raised her daughter, Susan Bassett Feldman, to be aware of her increased risk of breast cancer; her family history put Susan’s chances of developing the disease at 1 in 2, far above average.

Susan regularly examined her breasts for lumps and had frequent mammograms. At one point, she asked her doctor if she could undergo a prophylactic mastectomy--a procedure where the breast tissue is removed and replaced with implants to lessen cancer risk. She was discouraged from taking that radical step.

When she found a lump in her breast at age 40, Susan sought the best medicine had to offer--including undergoing harsh, experimental treatments when the cancer spread to her brain and spinal fluid. But the disease won out.

Susan spent her last months making each of her three children and her mother patchwork quilts and pillows. Colleen Casey stayed by her side, administering massive doses of morphine to ease Susan’s pain. Susan died March 3 at age 42.

Casey is dry-eyed as she says: “I thought I was helping my daughter do all the things that were necessary. And she followed all the rules. What is frustrating is that the results from treatment now are not a heck of a lot better than they were when I had cancer. I am watching her two daughters, ages 22 and 14. I’m hoping the outlook will be better for them, but I’m not sure it will. Twenty-five years after my cancer, why should I still be worried about my granddaughters?”

Casey folds the quilt and puts it in a closet.

“It is still a long, hard road before we conquer this dreadful disease.”

Few cancer experts would argue with that.

While optimism for the future is technically grounded in auspicious work in genetics, biotechnology, prevention, early detection and new drugs, almost half of all people who get cancer die from the disease within five years--about 514,000 deaths a year in the United States.

Survival rates have only increased 4.1% since the mid-1970s, making the National Cancer Institute’s 1985 goal of reducing cancer mortality by 50% by the year 2000 painfully remote.

Moreover, the incidence of cancer is increasing for reasons that are poorly understood. Breast cancer has increased about 3% a year since 1980; melanoma, 4% a year; prostate cancer, 2.8% a year. Among children under 14, brain tumors and leukemia incidence have soared over the last two decades.

At current rates, one of every three Americans can expect to develop cancer at some time in their lives. As life expectancy increases, cancers that are more common in old age--colon, prostate and breast--are also expected to continue to increase.

Despite its successes, the war on cancer has not resolved many troubling aspects of the disease.

Researchers promote cancer prevention and early detection as major tactics to greatly lower cancer death rates. But the realities of achieving either on a grand scale are far from certain.

Experimental new treatments such as gene therapy and the use of biological agents show great promise. But they are only now being tested and there is no guarantee that these are the answer, either.

In the meantime, physicians admit that they are left to strive for greater success by eking out improvements in the traditional forms of cancer treatment: surgery, radiation and chemotherapy. Each of these treatment approaches, so far, has serious limitations.

For example, people die of cancer largely because none of the current treatment approaches are very effective at stopping metastasis--malignant cells that have spread beyond the primary tumor to other parts of the body, said Dr. Lance Liotta, chief of the NCI’s laboratory of pathology.

“Metastasis is the real reason cancer is lethal,” Liotta said. “If we can control metastasis, we would really be able to prevent death.”

Even when there is no sign of disease in the lymph nodes--where the tissue cancer is likely to spread first--25% to 30% of patients probably still have “micro metastasis,” which cannot be seen in the cells examined under a microscope.

“In time, those cells will grow and become life-threatening. We need better markers to show when that might happen,” Liotta said.

When cancer is detected early, treatment is often overwhelmingly successful. But the opportunities for early detection are only beginning to emerge. Because of a lack of symptoms, ovarian, pancreatic and lung cancer typically are not discovered until later stages.

The failure to detect lung cancer is particularly troubling: The disease represents an estimated 28% of all cancer deaths. Lung cancer cannot be detected until the abnormal cells are large enough to be seen under a microscope. By then, the cancer has usually been growing for some time and may have spread. This fall, however, researchers at several investigative centers will begin using monoclonal antibodies, genetically engineered molecules that can be targeted to specific sites in the body to detect malignant cells in the sputum samples of people at high risk. Researchers hope that the new technique will allow them to detect the cancer much earlier, before the cellular changes and damage to the lungs are too great.

Scientists in the lung cancer study have an easy place to start targeting people for early detection--cigarette smokers. But, other than the use of tobacco, experts know little about what places individuals at high risk for cancer. Predicting what environmental or lifestyle factors cause cancer is largely guesswork. And the ability to identify the genes that predispose some people to certain cancers is little more than a goal.

“That is pie-in-the-sky prevention at this very moment,” said Helene G. Brown, director of community applications of research at the Jonsson Comprehensive Cancer Center at UCLA. “The prevention we’ve got now--we really haven’t gotten much to go on. Prevention is just as complex as treating disease.”

In the more immediate future, at least, any gains made in reducing cancer deaths are likely to emerge from improvements in the four current approaches to treating cancer: chemotherapy, radiation, surgery and, the newest, gene therapy. Each is limited in what it can achieve, researchers say.

Physicians are disappointed with the lack of major new classes of drugs that might do more than just nudge survival rates forward. Chemotherapy aims to interfere with cell growth and reproduction, either to cure the cancer or to prolong survival or simply relieve discomfort. However, cancer drugs--as opposed to the newer biological therapies--do not distinguish between normal cells and cancer cells, so a balance must be found between destroying the tumor and side effects caused by damaging healthy tissue.

While oncologists continue to experiment successfully with different combinations of chemotherapy on various cancers, taxol is the first distinctly new drug to surface since platinum drugs were introduced to fight cancer in the mid-1970s, said Dr. Ezra Greenspan, a pioneer in the use of combination chemotherapy who is now with the Mt. Sinai Medical Center in New York.

Taxol is made from the bark of the rare Pacific yew tree found in old-growth forests in British Columbia and the northwest United States. It is painstaking to gather--it takes the bark from about 38,000 mature trees to procure 55 pounds of taxol, enough for 1,200 patients. But taxol has been found to be successful in treating ovarian and breast cancer and may be useful in lung cancer and other solid tumors. In one recent study of 48 women with ovarian cancer so advanced all were expected to die within months, 30% showed a regression of the tumors and one woman’s cancer vanished.

Greenspan said that several obstacles will have to be overcome before everyone who can benefit from taxol will be able to get it, including years of clinical studies, environmental concerns about the way the drug is obtained, and funding difficulties. Research on the drug as a cancer agent began in earnest in 1979, and the drug is only now becoming available in clinical trials among women with advanced ovarian cancer.

“Taxol is the most recent, exciting new drug. But it will take another 10 years to get it on the market,” Greenspan said. “A big disappointment to me is that there aren’t more new drugs coming down the pike. You only get one or two major new drugs per 10 years. That’s terrible. That’s the result of (inadequate) funding.”

But even where money has produced multifaceted new strategies, some of the results have been less than hoped for.

In the field of radiation oncology, physicians cite a wealth of dazzling new high-tech equipment, such as three-dimensional scanners, computers and linear accelerators, and applaud their increasing ability to deliver therapy with fewer side effects.

The bad news is that radiation therapy has not advanced cure rates, said Dr. Eli Glatstein, chief of the NCI radiation oncology branch. While praising improvements that have led to fewer side effects from radiation and prolonged survival, Glatstein bemoans the bottom line.

“Radiation does not help the overall cure rate,” he said. “Survival is the single, most important end point. A patient is alive or dead. There is no doubt about that. Anything that doesn’t show a survival gain has to be interpreted with some caution.”

Particularly mystifying is the inability to know when radiation will be successful.

“Our inability to know in advance how tumors will respond to radiation is ridiculously poor,” he said. “You really don’t know until you try.”

Experts are also struggling to better target radiation to the tumor while avoiding damage to healthy cells. Many promising approaches to this problem are on the horizon. But for now, Glatstein said: “Every form of cancer treatment has some problem discriminating between normal tissue and tumor. There are no easy answers for this other than better tools.”

Better tools are also the hoped-for salvation of one of the most promising cancer treatments of the early 1980s--biological therapy. But disappointment lingers over the performance of biological therapies such as interferon and interleukin-2, which once were heralded as potential “magic bullets” to cure cancer.

“I think when these were first introduced people thought you could just take one and inject it and cure one or another disease,” said Dr. Michael W. Fanger of the Dartmouth-Hitchcock Medical Center in Hanover, N.H. “I think that outlook was very hopeful, but it was made without understanding their mechanisms for action. Certainly, the results have been very disappointing. We knew they would find the tumor cell, but how do they kill the cell?”

The latest approach in this field is to use agents called bi-specific antibodies that will act as bridges to link a tumor-identifying drug with a cancer-killing drug.

But according to Dr. Robert C. Young, a former president of the American Society of Clinical Oncology and now with the Fox Chase Cancer Center in Philadelphia: “These will only improve survival for some patients. And none of these approaches is likely to change the prognosis significantly for most advanced cancer patients.”

Finally, with only three limited studies under way, the potential of this fourth and newest approach--gene therapy--is unknown.

Speaking to a stuffy, standing-room-only ballroom at a meeting of the American Assn. for Cancer Research in May, NCI scientist Steven A. Rosenberg, the only researcher approved to use gene therapy, cautioned his colleagues that the present techniques are so complex and cumbersome that they could be administered only at a few, highly sophisticated cancer institutions. And, the therapy is still toxic to many patients.

Rosenberg expresses modest hopes for his clinical trials.

But the studies, he said, “have demonstrated that it is possible to use immunological therapies. And this may lead to a more practical approach.”

“It is possible that none of the approaches (in use today) will prove in the end to be the most effective ways of preventing and treating cancer,” Young said.

But promising new strategies, he warned, will not materialize unless government funding for cancer research is stepped up.

In Young’s view, the training, research and treatment infrastructure that has developed under the National Cancer Act during the last 20 years is in “grave danger” of collapsing.

The budget of the National Cancer Institute has dropped 6% in real dollars from 1980, Young said, resulting in research staff cutbacks.

The weakening of federal funding for cancer research in the last 10 years infuriates cancer researchers, many of whom take on the posture of politicians in white lab coats when given the opportunity to speak about their work.

“The tragedy now is that the scientific community is excited--they have the tools to solve the problems,” said Dr. Curtis C. Harris, chief of the NCI’s laboratory of human carcinogenesis. “But there is a concern and reluctance to put money in basic and applied research. This is the time to do it because we now have the tools. It’s not hype. The excitement is evident within the scientific community.”

Researchers who go before Congress to seek bigger cancer research budgets have, in recent years, encountered bruising interrogation on why cancer mortality statistics have not markedly improved, said Dr. Karen Antman of the Dana-Farber Cancer Institute in Boston.

Legislators have taken a view that the war on cancer has failed, she said.

“Congress looks at the bottom line--the number of Americans dying of cancer this year--when evaluating the return on their research appropriation dollars. One congressman asked me: ‘What have we got to show for it?’ Cancer researchers face this question all the time. The public perception is that there isn’t much to show for it.”

Public and government impatience is understandable, said Dr. Allan Herman, an expert on preventive health at the National Institutes of Health.

“I don’t think there is a failure yet, “ he saids of the war on cancer. “But we have to translate a lot of basic science into interventions. To do that there has to be political will.”

It is unclear whether Americans and their political representatives can demonstrate that will. Public outcry over the cancer death toll is almost nonexistent. But the pain in individual voices cannot be underestimated. It rings in the voice of Colleen Casey. It rings in the voice of Kathryn Underwood-Zimmer, 35, a Diamond Springs, Calif., woman who lost her father, William Underwood, 59, to cancer a few months ago.

Since then, Underwood-Zimmer has written letters to newspapers and local, state and federal authorities asking whether enough is being done to defeat cancer.

“I know losing a loved one is never easy under any circumstances. But I do not feel enough is being done in the fight against cancer,” she says in a letter she has sent around the country.

Underwood-Zimmer said it interests her “how people involved in the fight against AIDS make darn sure they are heard.”

Cancer deaths, she said, are neither seen nor heard.

“No one seems to be storming Washington. Hollywood has other causes. And the rest of us just hope it never hits home.

“Cancer and the lack of progress in the fight against it is not OK. The degree of apathy that surrounds this disease is not OK. The lack of understanding by both the medical society and society in general is not OK. . . . I don’t know what I can do about this situation. But I don’t feel sending my annual donation to the American Cancer Society and leaving it at that is enough.”