Trial Information

PROSPECTIVE RANDOMISED EVALUATION OF HIGH-INTENSITY CHEMOTHERAPY WITH PERIPHERAL BLOOD PROGENITOR SUPPORT IN PATIENTS WITH HIGH RISK BREAST CANCER

OBJECTIVES: I. Compare the efficacy of high dose cyclophosphamide and thiotepa with
peripheral blood stem cell support vs conventional cyclophosphamide, methotrexate, and
fluorouracil (CMF), both following doxorubicin induction, in women with high risk breast
cancer.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by the number of
positive axillary nodes (4-9 vs at least 10) and by center. Patients are randomized to one
of two treatment arms. Arm I: Patients receive induction therapy consisting of doxorubicin
IV every 3 weeks for 4 courses followed by consolidation therapy consisting of
cyclophosphamide IV, methotrexate IV, and fluorouracil IV every 3 weeks for 8 courses. At
week 4 of consolidation therapy, patients receive radiotherapy to the breast, chest wall,
and axilla over 3-5 weeks or as appropriate. Following recovery from consolidation therapy,
patients receive maintenance therapy consisting of oral tamoxifen daily for 5 years. Arm II:
Patients receive induction therapy as in arm I followed by consolidation therapy consisting
of stem cell mobilization with high dose cyclophosphamide IV over 2 hours and filgrastim
(G-CSF) subcutaneously beginning 24 hours after cyclophosphamide and continuing until blood
counts recover. At 13-28 days following peripheral blood stem cell (PBSC) collection and/or
autologous bone marrow collection, patients undergo chemoablation consisting of thiotepa IV
and cyclophosphamide IV continuously over 4 days followed 72 hours later by PBSC infusion
with or without autologous bone marrow. Following hematologic recovery, patients receive
radiotherapy and maintenance therapy as in arm I. Patients are followed every 6 months for 2
years, then annually.

PROJECTED ACCRUAL: More than 600 patients will be accrued for this study over 5 years.