The Doctor's World: Good News From the Front in War Against Cancer
By LAWRENCE K. ALTMAN (NY Times)
LOS ANGELES -- For weeks, a barrage of good news about cancer in people has come from scientists and public health officials.
In March, the government announced the first drop in the number of new cancer cases since the 1930s and a continued decline in cancer deaths.
A month later, jubilant National Cancer Institute officials identified the first drug to delay, if not necessarily prevent, breast cancer among women at high risk for the disease. Tamoxifen, which is now often prescribed to prevent a recurrence of breast cancer, was found in a study of high-risk women to reduce the risk of developing the disease in the first place by 45 percent.
Later in April, other studies showed that a second drug, raloxifene, apparently can reduce the risk of developing breast cancer without raising the risk of uterine cancer, a side effect of tamoxifen.
Last week, more good news about innovative approaches to controlling cancer came, surprisingly, from oncologists, the doctors who treat cancer patients. They are traditionally cautious and skeptical about treatment claims. Many of the 18,000 cancer specialists at the annual meeting of the American Society of Clinical Oncology spoke enthusiastically about reports reflecting the cutting edge of research.
"It is new for ASCO to have this amount of information from clinical trials," said Dr. Lynn Schuchter, particularly from early-stage studies of experimental drugs. Dr. Schuchter, of the University of Pennsylvania, heads the society's public relations committee.
Taken together, the findings provide important guideposts for the next skirmishes in the decades-old war on cancer. With standard cell-killing chemotherapy pushed to its limits, oncologists predict that the next wave of therapies is most likely to come from laboratory findings about genetic defects that are presumed to give rise to cancer.
However, the meeting highlighted the fact that as cancer care increases in complexity, many doctors are not putting newer knowledge into practice. For their part, many of the doctors said society must do more to make new or experimental treatments available.
Though some reports detailed the failure of seemingly promising experimental drugs, and though the scientists worried about offering honest hope, not unwarranted hype, some were a bit looser in using the word "cure" than most of their colleagues have been in the past.
(The meeting dealt with new and experimental treatments that have been tested in people, not animal research like the continuing development of drugs that seem to eliminate cancer in mice by preventing the growth of tumor blood vessels. The New York Times was repeatedly criticized at the meeting for a recent report on this work. While not criticizing the research itself, doctors said The Times' reporting of it was premature. Several leaders said that as the article noted, in the past a number of experimental drugs cured cancer in mice but proved ineffective or too dangerous in humans.)
The change in outlook among oncologists was striking, and there were many reasons for it.
One is the contention of many oncologists that they are at a critical point in cancer care. Many here said they believed recent laboratory advances in molecular biology and genetics are poised to offer new improvements in treatments for people.
Another is that clinical trials have found new uses for older drugs, raising hopes that they may turn some forms of cancer into a manageable chronic disease. Leaders expressed hope that anti-cancer drugs will soon begin to keep a tumor in check for decades, much as insulin keeps diabetics alive without curing diabetes.
The gains reflect an investment of billions of dollars, by taxpayers and industry, in research. Under pressure from elected officials and shareholders to justify investments, scientists have stepped up their public relations efforts to show results, even minor ones.
Advances in cancer treatment generally come in steps. It would be astonishing if any single therapy worked against the scores of diseases known collectively as cancer. So far, anti-cancer drugs generally have proved more effective in combinations than singly.
Most reports here concerned the potential of adding new drugs to such combinations. Others involved the so-called proof-of concept, which means that researchers proved the scientific principle underlying an experiment. However, research may still be required beyond such proof to produce a useful therapy. Still other reports related to experimental drugs that the Food and Drug Administration has not licensed.
It usually takes five or more years to complete tests of experimental anti-cancer drugs. The FDA generally requires full-scale studies in large numbers of patients in two or more hospitals before approving a drug for marketing.
Until the drugs are approved, the federal Medicare program and most other health-insurance plans will not pay for them. A full course of many of the still-experimental anti-cancer therapies costs several thousand dollars.
One of the most striking results, described in a news release issued at the meeting, involved work by scientists at the University of California at Los Angeles. The university said that its scientists had helped to develop an experimental drug, Herceptin, for a particular type of cancer that is involved in 30 percent of breast cancers.
The FDA has not approved Herceptin for marketing. For now, Herceptin is available only to those in clinical trials and by lottery to a few hundred others.
But other reports described new, non-FDA-approved uses of marketed drugs. Doctors are legally free to prescribe a marketed drug for a condition for which it has not been approved, if they believe it will benefit a patient. The process is known as off-label use.
Oncologists were also excited about a new use for Taxol, which has been in use for advanced forms of breast cancer. In a study of a new use -- in early breast cancer -- Taxol reduced the death rate when combined with standard anti-cancer drugs.
Taxol was hailed as the first new drug in 15 years for adjuvant breast-cancer therapy. Adjuvant therapy aims to prevent recurrences of cancer, and leaders said the findings would begin to change breast-cancer care as soon as this week.
Manufacturers are often eager to exploit such opportunities for new sales. And scientists, proud of their research that showed a new therapy worked, often encourage off-label use to enhance their reputations.
But it is often difficult for doctors to reach a consensus on when such a drug should come into wider use.
The news about tamoxifen and raloxifene has led experts to debate when to use each drug and whom to treat with it. Because the studies of the drugs were conducted in different ways, the National Cancer Institute wants to conduct a new study comparing them head-to-head. Critics say that it would be difficult to recruit women for such a clinical trial, and many oncologists say that raloxifene should be prescribed on the basis of existing information.
Dr. Craig Henderson of the University of California at San Francisco said that about 25 newer kinds of biological products might be developed to treat cancer, but that it would take years and tremendous effort to organize and conduct the clinical trials to prove their effectiveness. "It is not as if suddenly the skies are going to open," dropping important new drugs, Henderson said.
Oncologists repeatedly lobbied journalists at the meeting to publicize a need for the government to spend more money for clinical trials. Additional pressures for publicizing findings come from marketing experts who seek to promote medical centers.
In seeking to present a favorable view of an experimental drug in presentations to those attending the meeting, a few oncologists seemed to gloss over dangerous side effects seen in early-stage testing.
These effects are reported in highly technical summaries of the meeting's 2,000 presentations, which the society published in a book and posted on the Internet (www.asco.org). However, only a rare doctor would read all the summaries.
Moreover, they are far less detailed than the full medical articles that will take months, if not years, for the researchers to write and scientific journals to publish. Even then, the journal reports are likely to paint a rosier picture than will the information that manufacturers are required to submit to the FDA.
The drugs that Henderson and other leaders think could be developed derive from research in molecular biology and genetics.
Scientists now "accept as gospel that all cancers are genetic diseases" and that "at the heart of all cancerous cells you will find a genetic alteration," said Dr. Kenneth Offit of Memorial Sloan-Kettering Cancer Center in New York.
Many such genetic changes are not inherited, but are acquired in ways that scientists do not understand.
Researchers are trying to exploit information about defective genes in trying to develop drugs that will kill only cancerous cells, unlike those in standard chemotherapy that kill healthy cells as well.
Public announcements about advances in cancer often lead patients and their families to call their doctors and demand the new treatments. In 1998, more than 1.2 million Americans will be newly diagnosed with cancers, joining millions of others struggling with the disease.
Although the experimental therapies may extend or save the lives of many of these people, they are coming too late to help the more than 560,000 Americans who will die of cancer this year.
Surveys reported at the meeting found deficiencies in the way many oncologists deal with end-of-life care.
In one survey, oncologists said pain management was a high priority. But the same doctors displayed surprising ignorance when asked about simple manipulations to improve pain therapy, said Dr. Kathleen Foley of Memorial Sloan-Kettering Cancer Center, who conducted the survey.
Another survey of 3,200 oncologists in the United States, Canada and England found that most learned by trial and error how to care for dying patients. Only 20 percent said they learned in formal courses, and 25 percent said that caring for the dying was the worst part of their jobs.
The survey underscored the need to vastly improve medical training to provide the skills for end-of-life care, said the primary author, Dr. Ezekiel Emanuel of the National Institutes of Health.
Despite the barrage of good news, the day when all cancers will be cured seems far off. Until then, the sad reality is that doctors will need to hone their skills in helping patients with incurable cancers die.
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