Trial Information

Phase II Trial of Sequential High-Dose Alkylating Agents in Metastatic Breast Cancer

OBJECTIVES: I. Determine the feasibility and efficacy of sequential high-dose
cyclophosphamide, melphalan, and thiotepa plus autologous peripheral blood stem cell rescue
in patients with metastatic breast cancer with ongoing objective response to prior induction
chemotherapy.

OUTLINE: Patients receive sequential therapy beginning with regimen A. Regimen A: Patients
receive cyclophosphamide IV over 1 hour every 6 hours or more for 4 doses within 36 hours.
Patients receive filgrastim (G-CSF) subcutaneously (SC) daily beginning 2 days after
completion of cyclophosphamide and continuing until autologous peripheral blood stem cells
(PBSC) are harvested. Regimen B: Beginning at least 3 weeks after initiation of regimen A,
patients receive melphalan IV on days 1 and 2. Beginning on day 4, a portion of the PBSC are
reinfused. Patients receive G-CSF SC daily beginning on day 4 and continuing until at least
day 10. Regimen C: Beginning at least 3 weeks after initiation of regimen B, patients
receive thiotepa IV over 2 hours on days 1 and 2. Beginning on day 5, the remaining PBSC are
reinfused. Patients receive G-CSF SC daily beginning on day 5 and continuing until blood
counts recover. During regimens A, B, and C, G-CSF must be discontinued at least 2 days
before administration of any chemotherapy. Regimen D: After recovery from chemotherapy,
patients with hormone receptor-positive tumors and no prior refractoriness to hormonal
therapies receive oral tamoxifen daily, while patients with prior failure on tamoxifen
receive oral megestrol 4 times daily. Patients undergo irradiation to sites of prior
cutaneous, nodal, bone, or soft tissue bulk disease and resection of residual lesions.
Patients are followed weekly for 1 month, biweekly for 2 months, monthly for 5 months, and
then bimonthly for 1 year.

PROJECTED ACCRUAL: A minimum of 30 patients will be accrued for this study.