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Substitution of Docetaxel for 5-Fluorouracil in Standard Early Breast Cancer Chemotherapy Reduces Risk of Death and Cancer Recurrence: Presented at SABCS

By Bruce Sylvester

SAN ANTONIO, TX -- December 8, 2003 -- The substitution of docetaxel (Taxotere) for 5-fluorouracil in the standard FAC (5-fluorouracil, Adriamycin and Cytoxan) adjuvant treatment of women with node-positive early breast cancer has produced a dramatic 30% reduction in relative risk of death and a 28% reduction in relative risk of cancer recurrence, researchers reported December 5^th in a late-breaking session here at the 26^th Annual San Antonio Breast Cancer Symposium.

The new regimen under study is called TAC (Taxotere, Adriamycin and Cytoxan).

"These results, which have astounded and pleased all of us, show that the simple replacement of one drug for another can, potentially, help tens of thousands of women live longer each year and reduce their risk of relapse," said John Mackey, MD, co-investigator from the department of oncology at the University of Alberta in Alberta, Canada, and clinical oncologist at the Cross Cancer institute in Edmonton, Canada.

The Breast Cancer International Research Group (BCIRG), a global cooperative of oncology researchers, enrolled 1,491 patients from June 1997 to June 1999. The investigators randomized 745 subjects to TAC and 746 to FAC. They designed the study to analyze data on subgroups of subjects based on hormone receptor status (positive and negative) and nodal involvement (1-3 or 4+ axillary lymph nodes). They prospectively collected tumor samples for 95% of the subjects. An independent pathologist reviewed hormonal receptor status, HER2neu amplification and other tumor characteristics.

The first planned interim analysis with a median follow-up of 33 months and 289 events was presented at the American Society of Clinical Oncology meeting in 2002 (Abstract 141); it indicated statistically significant improvement in disease-free survival (DFS) in favor of TAC. As the promising survival data from the first analysis emerged, the independent oversight committee for the trial ordered a second interim analysis at 55 months. "This is the second interim analysis at a median follow-up of 55 months with 399 DFS events. A statistical boundary of 0.001 for DFS adjusted for nodal (N) status was defined for this analysis," the investigators noted.

At 55 months, 75% of TAC subjects and 68% of FAC subjects remained disease-free. This indicates a 28% reduction in the relative risk of disease recurrence (P = .0010). As for survival, 87% of TAC patients and 81% of FAC patients were alive at 55 months, indicating a 30% reduction in relative risk of mortality (P = .0080) in favor of TAC.

The researchers also saw the statistically significant benefits from TAC in both hormone-receptor-positive and hormone-receptor-negative subjects, with a reduction of relative recurrence of disease of 27% and 34%, respectively. They also saw statistically significant disease-free survival benefit for TAC subjects independent of Her2neu expression.

In a BCIRG statement, Dennis Slamon, MD, chief of the division of hematology-oncology at UCLA School of Medicine in Los Angeles said, "This study confirms that Taxotere is a very compelling component of future combinations being developed for the treatment of early stage breast cancer with new therapies coming from biological research."

Docetaxel is currently FDA-approved for the treatment of patients with locally advanced or metastatic breast cancer after failure of chemotherapy, for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer after failure of platinum-based chemotherapy, and in combination with cisplatin for the treatment of patients with unresectable, locally advanced or metastatic non-small-cell lung cancer who have not previously received chemotherapy for this condition.


[Study title: TAC Improves Disease-Free Survival and Overall Survival Over FAC in Node-Positive Early Breast Cancer Patients, BCIRG 001: 55 Months Follow-Up.]

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