Trial Information

A RANDOMIZED TRIAL COMPARING PREOPERATIVE DOXORUBICIN (ADRIAMYCIN)/CYCLOPHOSPHAMIDE (AC) TO PREOPERATIVE AC FOLLOWED BY PREOPERATIVE DOCETAXEL (TAXOTERE) AND TO PREOPERATIVE AC FOLLOWED BY POSTOPERATIVE DOCETAXEL IN PATIENTS WITH OPERABLE CARCINOMA OF THE BREAST

OBJECTIVES: I. Compare overall and disease-free survival in patients with operable
adenocarcinoma of the breast treated with 4 courses of preoperative doxorubicin and
cyclophosphamide (AC) alone vs 4 courses of preoperative or postoperative docetaxel (TXT)
following 4 courses of preoperative AC. II. Evaluate whether the addition of preoperative
TXT to preoperative AC results in improved rates of clinical and pathologic locoregional
tumor response. III. Assess whether the addition of preoperative TXT to preoperative AC
results in improved rates of breast conservation. IV. Assess whether postoperative TXT
improves disease-free and overall survival in patients who receive preoperative AC,
especially in certain subgroups of patients (e.g., those with pathologically positive
nodes).

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age
(under 50 vs 50 and over), clinical tumor size (less than 2.1 cm vs 2.1-4.0 cm vs greater
than 4.0 cm), clinical nodal status (negative vs positive), and participating center.
Patients are randomized to one of three treatment arms. Arm I: Patients receive doxorubicin
IV followed by cyclophosphamide IV over 30 minutes to 2 hours on day 1 every 21 days for 4
courses. Patients receive oral tamoxifen daily for 5 years, starting on day 1. After
completion of chemotherapy, patients are offered surgery (e.g., lumpectomy with axillary
node dissection, or modified radical mastectomy). Post-operative radiotherapy is given
post-lumpectomy. Arm II: Patients receive doxorubicin IV followed by cyclophosphamide IV
over 30 minutes to 2 hours followed by docetaxel IV over 1 hour on day 1 once every 21 days
for 4 courses. Patients receive oral tamoxifen daily for 5 years, starting on day 1. After
the completion of chemotherapy, surgery is offered (as in arm I). Radiotherapy follows
surgery in post-lumpectomy patients. Arm III: Patients receive doxorubicin IV followed by
cyclophosphamide IV over 30 minutes to 2 hours on day 1 every 21 days for 4 courses.
Patients receive oral tamoxifen daily for 5 years, starting on day 1. After completion of
chemotherapy, surgery is offered (as in arm I). After surgical recovery, docetaxel IV is
given over 1 hour once every 21 days for 4 courses. Radiotherapy follows docetaxel in
post-lumpectomy patients. Chemotherapy is repeated every 21 days for 4 courses in the
absence of disease progression or unacceptable toxicity. Patients are followed every 6
months for 5 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 2,400 patients will be accrued for this study within 5
years.