Repeated Bone Marrow Transplantation in Treating Women With Advanced Breast Cancer

OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of samarium 153 used sequentially with autologous bone marrow transplantation for metastatic breast cancer. II. Determine the response rate, median duration of response, and overall survival of patients who respond to induction therapy followed by 2 cycles of high dose chemotherapy and stem cell support.

OUTLINE: This is a dose escalation study. Patients are first treated with salvage chemotherapy for no more than 4 cycles. At least a partial remission must be achieved. Peripheral blood stem cells (PBSC) are collected following the administration of filgrastim (granulocyte colony-stimulating factor; G-CSF). After recovery from the prior chemotherapy, high dose chemotherapy begins. Paclitaxel is administered as a 24 hour infusion on day -7. Melphalan IV is administered over 1 hour on days -6 and -5. PBSC are infused on day 0. A second regimen of high dose chemotherapy begins after at least 42 days posttransplant and as long as at least partial remission occurs after previous chemotherapy. Samarium 153 is administered on day -14. Cohorts of 3 patients each are treated at each dose level until the maximum tolerated dose is reached (defined as dose at which the dose limiting toxicity occurs in 3 or more of 6 patients). Cyclophosphamide, thiotepa, and carboplatin are infused over 24 hours on days -7 through -4. PBSC are infused on day 0 followed by G-CSF IV. The phase II dose of samarium 153 is one dose level below the MTD determined in the Phase I portion of this study. Patients are followed until death.

PROJECTED ACCRUAL: At least 12 patients will be accrued for this study.