A Phase III Study of Doxorubicin-Cyclophosphamide Therapy Followed by Paclitaxel or Docetaxel Given Weekly or Every 3 Weeks in Patients With Axillary Node-Positive Breast Cancer

OBJECTIVES:

• Compare the disease-free survival and overall survival in patients with node-positive or high-risk node-negative operable stage II or IIIA breast cancer treated with docetaxel or paclitaxel after doxorubicin and cyclophosphamide.
• Determine whether the weekly administration of paclitaxel or docetaxel for 12 weeks improves disease-free survival and overall survival when compared with the conventional schedule of every 3 weeks for 4 courses after doxorubicin and cyclophosphamide in this patient population.
• Compare the toxic effects of docetaxel and paclitaxel when administered weekly for 12 weeks versus every 3 weeks for 4 courses in these patients.
• Compare the toxicity of paclitaxel administered every 3 weeks for 4 courses or weekly for 12 weeks to that of docetaxel administered on the same schedules in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to estrogen receptor status (positive vs negative vs unknown), nodal status (0 positive nodes vs 1-3 positive nodes vs 4-9 positive nodes vs at least 10 positive nodes), tumor size (no more than 5 cm vs more than 5 cm vs unknown), and type of prior surgery (mastectomy vs breast conservation surgery). Patients are randomized to one of four treatment arms.

• Arm I: Patients receive doxorubicin IV and cyclophosphamide IV every 3 weeks for 4 courses (weeks 1-12). Beginning at week 13, patients receive paclitaxel IV over 3 hours every 3 weeks for 4 courses.
• Arm II: Patients receive doxorubicin and cyclophosphamide as in arm I. Beginning at week 13, patients receive paclitaxel IV over 1 hour weekly for 12 weeks.
• Arm III: Patients receive doxorubicin and cyclophosphamide as in arm I. Beginning at week 13, patients receive docetaxel IV over 1 hour every 3 weeks for 4 courses.
• Arm IV: Patients receive doxorubicin and cyclophosphamide as in arm I. Beginning at week 13, patients receive docetaxel IV over 1 hour weekly for 12 weeks.

Within 4 weeks after completion of chemotherapy, patients with estrogen and/or progesterone receptor positive tumors receive oral tamoxifen daily for 5 years.