Trial Information

A Comparison of Intensive Sequential Chemotherapy Using Doxorubicin Plus Paclitaxel Plus Cyclophosphamide With High Dose Chemotherapy and Autologous Hematopoietic Progenitor Cell Support for Primary Breast Cancer in Women With 4-9 Involved Axillary Lymph Nodes

OBJECTIVES: I. Compare disease free survival and overall survival in women with operable
breast cancer and at least 4 positive axillary lymph nodes treated with intensive sequential
chemotherapy with doxorubicin, paclitaxel, and cyclophosphamide versus standard dose
doxorubicin and cyclophosphamide followed by high dose STAMP I (cyclophosphamide, cisplatin,
and carmustine) or STAMP V (cyclophosphamide, carboplatin, and thiotepa) and autologous stem
cell rescue. II. Compare the toxic effects of these regimens in this patient population.
III. Measure the breast cancer cell content of the peripheral blood progenitor cell (PBPC)
fractions from patients randomized to the PBPC supported arm and correlate the results with
the disease free survival, survival, and pattern of relapse in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by center, primary
treatment (mastectomy alone vs mastectomy plus radiotherapy following chemotherapy vs breast
conserving surgery plus radiotherapy following chemotherapy), menopausal status
(premenopausal vs postmenopausal), estrogen and/or progesterone receptor status (positive vs
negative vs unknown), N2 disease (yes vs no), T3 disease (yes vs no), myeloablative
chemotherapy regimen (STAMP I vs STAMP V), and source of progenitor cells (marrow vs
peripheral blood vs both). Patients are randomized to 1 of 2 treatment arms: Arm I: Patients
receive doxorubicin IV over 1 hour on days 1, 15, and 29, paclitaxel IV over 24 hours on
days 43, 57, and 71, and cyclophosphamide IV over 1 hour on days 85, 99, and 113. Patients
receive filgrastim (G-CSF) subcutaneously on days 3-10, 17-24, 31-38, 45-52, 59-66, 73-80,
87-94, 101-108, and 115-122. Arm II: Mobilization chemotherapy: Patients receive doxorubicin
IV over 1 hour and cyclophosphamide IV over 1 hour on days 1, 22, 43, and 64. Harvest:
Patients undergo harvest of autologous bone marrow and/or peripheral blood stem cells
(PBSC). Patients who undergo harvest of PBSC alone do not receive mobilization chemotherapy
but receive hematopoietic growth factors prior to harvest. High dose myeloablative
chemotherapy: Patients receive STAMP I OR STAMP V: STAMP I: Patients receive
cyclophosphamide IV over 1 hour and cisplatin IV over 24 hours on days -6 to -4 and
carmustine IV over 2 hour on day -3. STAMP V: Patients receive cyclophosphamide IV over 24
hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4.
Transplantation: Autologous bone marrow and/or PBSC are reinfused on day 0. Both arms:
Patients who are postmenopausal or who have hormone receptor positive disease receive oral
tamoxifen daily beginning 4 weeks after the completion of chemotherapy and continuing for 5
years. Patients who underwent breast conserving surgery receive locoregional radiotherapy 5
days a week for 4.5-5.5 weeks beginning 4-6 weeks after the completion of chemotherapy.
Patients who underwent modified radical mastectomy may receive locoregional radiotherapy 5
days a week for 5 weeks at the discretion of their physician. Patients are followed every 4
months for 3 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,000 patients (500 per arm) will be accrued for this study
within 5 years.