Breast Cancer Drug Test Halted

A study in which women with breast cancer were given two chemotherapy drugs simultaneously was cut short after the combination contributed to the deaths of two patients and caused life-threatening complications in an alarming number of others.

The problems developed in women given the standard intravenous drug doxorubicin along with a newer drug called docetaxel. The two drugs are frequently used alone to treat breast cancer. Scientists have been exploring the effects of combining them, with mixed results so far.

Docetaxel, or Taxotere, belongs to a class of cancer drugs that also includes Taxol. These drugs are derived from the yew tree and have shown promise in improving cancer survival.

French researchers set out to compare five-year, disease-free survival rates in 627 women treated with either doxorubicin plus Taxotere or the more conventional combination of doxorubicin plus cyclophosphamide. But they stopped the study after a little over three years, in 2003.

The patients who died had developed low white blood cell counts, fever and severe intestinal problems. A third woman became severely ill with similar symptoms.
Low white-cell counts with fever developed in nearly 41 percent of the doxorubicin-Taxotere women, compared with 7 percent of the other patients. The condition is a potential side effect of chemotherapy and can be life-threatening because it means the drugs have weakened the body's ability to fight infection.

The high rate of complications indicated the two-drug combination was too toxic, said the researchers, led by Dr. Etienne Brain of the Rene Huguenin Cancer Center in Saint-Cloud, France.

The study appears in Wednesday's Journal of the American Medical Association.

Dr. Carolyn Runowicz, president-elect of the American Cancer Society and an oncologist at the University of Connecticut, said the combination should not be abandoned because there is still a chance that it could improve survival. But it should be used with drugs to boost white-cell counts as a precaution, she said.

In a study presented over the weekend, Dr. Lori Goldstein of Fox Chase Cancer Center in Philadelphia compared the same two-drug combinations for treating early breast cancer.

There were four treatment-related deaths among the nearly 3,000 women studied — all in women on the Taxotere combination — but Goldstein said that rate was acceptably low. She found no difference in survival rates over nearly five years, but low white-cell counts with fever were more common in patients on the Taxotere combination.

Participants in the French study had a high chance of cancer recurrence because the cancer had reached their lymph nodes or because they had other risk factors.

By Lindsey Tanner