As reported by The Los Angeles Times, May 18, 2005.

Deaths Halt Chemotherapy Study

Two patients die and others suffer severe complications in a trial combining two drugs to treat breast cancer, researchers say.

By The Associated Press

CHICAGO — A study in which women with breast cancer were given two chemotherapy drugs simultaneously was cut short, researchers said, 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, known by the brand name Adriamycin, along with the newer drug docetaxel, or Taxotere. The two drugs are used individually to treat breast cancer. Scientists have been exploring the effects of combining them, with mixed results.

The study appears in today's Journal of the American Medical Assn.

Docetaxel belongs to a class of cancer drugs that also includes paclitaxel, or 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 docetaxel or the more conventional combination of doxorubicin plus cyclophosphamide, marketed as Cytoxan. But they stopped the study after a little more than three years, in 2003.

The patients who died had 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 about 41% of the doxorubicin-docetaxel patients, compared with 7% 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 that 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.

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 was still a chance that it could improve survival. But it should be used with drugs to boost white-cell counts, 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 docetaxel combination — but Goldstein said that rate was acceptably low. She found no difference in survival rates over about five years, but low white-cell counts with fever were more common in patients on the docetaxel 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.