BEATING CANCER; ONSLAUGHT OF EXPERIMENTAL THERAPIES HERALDS ERA OF OPTIMISM.

Byline: Daniel Q. Haney Associated Press

With good reason, cancer docs are the greatest skeptics in the conservative art of healing. Yet even these cautious souls stretch for superlatives when describing the changes sweeping over them.

Their big annual meeting, which concluded Tuesday in Los Angeles, is ordinarily a rather gloomy affair. Advances, when they happen at all, inch forward glacially. Much of what looks promising in test tubes and lab mice turns out to be a bust when tried on sick people.

``We see this stuff go by, year after year, and nothing works,'' said Dr. Craig Henderson of the University of California, San Francisco. ``If you are a practicing doctor, you have to be skeptical. All of a sudden, we are entering a new era.''

The new era is one of exquisitely targeted therapy. The blunderbuss approach of chemotherapy - poisons that kill good cells and bad ones alike, often with frightful side effects - will be augmented or even replaced by chemicals that zero in on malignant cells and leave healthy ones alone.

``This is the beginning of a large tidal wave,'' said Dr. Laura Hutchins of the Arkansas Cancer Research Center in Little Rock, Ark.

Traditionally, scientists have tackled cancer by screening thousands of compounds in the lab, hoping to stumble over one that kills tumors more efficiently than it kills normal growth. Researchers often test medicines with little real understanding of how they do whatever they do.

The new approach comes from the opposite direction: Understand what's wrong inside the cancerous cell, then design a medicine that corrects just that.

``Throwing bigger bombs at the disease wasn't going to get us a lot further,'' said Dr. Dennis Slamon of the University of California, Los Angeles. ``If we show what's broken and target it, we may be able to develop more effective and less toxic therapies.''

The fundamental difference between cancerous and normal cells lies in the genes. Genetic errors, accumulated over a lifetime, turn good cells into bad ones that escape the normal cycle of life and death.

At this week's meeting of the American Society for Clinical Oncology, Slamon and scientists from the biotech firm Genentech showed how understanding these genetic miscues can pay off with a unique new therapy.

Slamon laid the foundation with basic research that showed how some particularly aggressive forms of breast cancer escape the body's usual controls: The cancerous cells' genetic mistake makes them overreact to growth-stimulating hormones. Knowing this, Genentech set about crafting a solution - and cloned an antibody, named Herceptin, that blocks the cancerous cell's ability to receive the growth hormone.

Results released at the meeting show the approach works. While no magic bullet, it significantly increases the effects of traditional chemotherapy in terminally ill cancer patients and may be even more impressive when given earlier in the disease.

Yet perhaps more important even than developing a new cancer drug is what the process shows about science's potential ability to control cancer by going to its genetic core.

``This is not like anything we have ever seen before,'' said Dr. Larry Norton of Memorial Sloan-Kettering Cancer Center in New York City. ``This opens up a whole new chapter in the development of anti-cancer therapy.''

Most other therapies designed to exploit cancer's unique vulnerabilities are less far along than Herceptin, which Genentech hopes to have on the market in the fall.

Another idea is to use drugs to thwart the tumor's ability to connect with the blood supply of surrounding healthy tissue. In theory, a cancer starved of blood will not grow and spread.

``There is a coming together of focus,'' said Dr. Derek Raghavan of the University of Southern California. ``Science has actually made some real progress in the past 12 months.''

Some of the good news involves preventive measures rather than potential treatments for existing cancers. One study offers the first tentative evidence that checking blood with the PSA test, which stands for prostate specific antigen and is now a standard part of checkups for men over 50, saves lives by spotting prostate cancer early. Another suggests that the brittle-bone drug raloxifene may reduce the risk of breast cancer by two-thirds in older women.

Even the most optimistic projections, however, stop short of hinting at any across-the-board cure. It's more likely, doctors say, that these approaches will make cancer a more manageable disease, like diabetes or high-blood pressure.

``We won't wake up one day with a cure for cancer,'' Henderson said. ``But if we can make you live 20 years with your disease, and you die of something else, what's wrong with that?''

NEW DEVELOPMENTS

Among developments reported at this week's meeting of the American Society of Clinical Oncology:

The Genentech drug Herceptin is the first proven cancer medicine that works by attacking the genetic defects that cause the disease. Given to women with advanced breast cancer, it increases survival an average of three months. Experts hope for more dramatic effects when it's given in earlier stages of the disease.

Raloxifene, a medicine developed for the brittle-bone disease osteoporosis, appears to cut older women's risk of breast cancer by about two-thirds without raising the hazard of uterine cancer.

An eight-year follow-up study in Quebec found that the PSA test, a standard part of older men's checkups, sharply reduces the risk of dying from prostate cancer by finding the disease in treatable early stages. Skeptics caution this does not settle the controversy of whether testing and early detection actually translates into longer life for men already in their later years.

A vitamin A derivative called 13-cis-retinoic acid is effective in the childhood nervous system cancer called neuroblastoma, which strikes 500 people in the United States each year. Survival after three years was 55 percent in the vitamin patients, compared with 13 percent among those getting standard chemotherapy.

Taxol, a standard drug for advanced breast cancer, also works if given in early stages of the disease. A large study of women whose cancer had spread only to the lymph nodes found taxol increased survival after two years by 2 percentage points, to 97.

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BOX: NEW DEVELOPMENTS (see text)