http://www.nytimes.com/2002/12/12/health/12CND-CANC.html
new study has found that giving chemotherapy every two weeks instead of the
usual three significantly delayed relapses and improved the survival of women
with breast cancer. Reporting the findings yesterday, doctors said it could
prompt a major change in the way breast-cancer patients — and perhaps even
people with other kinds of cancer — are treated.
Only 18 percent of women who got the more frequent treatment suffered recurrences of their cancer within four years, compared with 25 percent who received the conventional treatment. And only 8 percent died within three years, as against 10 percent for the usual treatment. While that difference seems small, it could translate into thousands of lives saved each year, doctors said.
"I cried when I saw those numbers," said Dr. Larry Norton, director of the solid tumor division at Memorial Sloan-Kettering Cancer Center in New York and senior author of the study, which involved 2,000 women treated at hospitals across the nation.
"There's nothing not to love about the regimen," he went on. "It's less toxic. It's over in one-third less time and it decreases the death rate. So why wouldn't you want to use it?"
Doctors did note that the two-week regimen would be significantly more expensive, because it would require extra doses of a costly drug that stimulates the growth of white blood cells.
The results, announced at the annual San Antonio Breast Cancer Symposium, are setting off a debate among doctors over whether to change the standard treatment for breast cancer.
Dr. Charles L. Loprinzi, chairman of medical oncology at the Mayo Clinic, who was not a participant in the study, said, "I am very impressed by it, to the point where I think this is going to make a change in practice."
But Dr. Marc L. Citron, the principal investigator in the trial, was more cautious, saying it remained to be seen whether the higher survival rates would hold up over time, without adverse side effects. "I'm not going to hang my hat on survival," said Dr. Citron, a clinical professor at Albert Einstein College of Medicine.
Dr. Peter M. Ravdin, of the University of Texas Health Sciences Center in San Antonio, said some drugs that seemed to reduce death after two or three years did not improve survival over a longer period. "It's not unusual to have recurrences at five or even after five years," he said.
Some doctors said more frequent chemotherapy might also be useful to treat other types of cancer, though most doctors are not expected to switch until clinical trials prove the advantages.
Based in part on mathematical models of tumor growth developed by Dr. Norton and Dr. Richard Simon of the National Cancer Institute, scientists have long theorized that more frequent chemotherapy would work better because it would give the tumor cells less time to grow back before being hit by the drugs again.
But doctors usually wait three weeks between courses, partly because the drugs cause a sharp decrease in white blood cells that fight infection and partly because the body needs time to recover.
In this trial, which was sponsored by the National Cancer Institute, patients who got the more frequent, or "dose-dense," chemotherapy were given an additional drug, Neupogen, that stimulated their body to produce white blood cells, allowing their white cell levels to recover faster.
The patients getting the dose-dense treatment had far fewer episodes of low white cells than those getting conventional chemotherapy, who did not get the white cell stimulant. In general, the more frequent doses did not increase toxicity, though they did increase the need for transfusions of red blood cells.
If more frequent treatments catch on, it could be a windfall for
But Neupogen used in this way could also more than double the cost of treatment. Dr. Loprinzi of the Mayo Clinic calculated that the Neupogen used in the trial cost $15,000 to $24,000 per patient depending on the dose. That is more than the $13,000 cost of the chemotherapy drugs. Still, he and others said, if the addition of Neupogen reduced relapses and deaths, it could represent a net cost saving.
The clinical trial enrolled women who had had their tumors removed by surgery but who were receiving three standard chemotherapy drugs to prevent a recurrence. The total amount of drug received was the same for all the patients.
Scientists said that the more frequent chemotherapy reduced the relative risk of death by 31 percent. That is roughly the same reduction achieved by giving chemotherapy compared to not giving chemotherapy.
That is not intuitively obvious since the death rate was reduced from 10 percent to 8 percent after three years. But that drop of 2 percentage points on an absolute basis is a drop of 20 percent — 2 out of 10 — on a relative basis. The figure became 31 percent after other adjustments. Similarly, the risk of relapse was reduced 26 percent by the dose-dense chemotherapy.
Still, the fact that 90 percent of the women who got the conventional chemotherapy were alive after three years, compared to 92 percent for the accelerated therapy, meant that all patients did fairly well, which could make the case for switching schedules somewhat weaker, some doctors said. "It doesn't trump every other option that exists, let's put it that way," said Dr. William J. Gradishar, director of breast oncology at Northwestern University, one of the authors of the study.
Another potential drawback is that Neupogen, the white blood cell booster, requires a daily injection for eight consecutive days with each round of chemotherapy. But Amgen has developed a new drug, Neulasta, that requires only one injection per round.
Scientists have tried before to give higher doses. For years, it was believed that women with breast cancer could be helped by giving them a huge burst of chemotherapy all at once, then rebuilding their white blood cell levels through a bone marrow transplant. But large clinical trials a few years ago showed that that did not lead to better outcomes.
The trial also compared giving the three chemotherapy drugs one at a time, each in its own round, to the standard practice of giving two of them together followed by the third. That did not result in statistically significant differences in relapses or survival.
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