High Dose Paclitaxel Added to Cyclophosphamide and Thiotepa Followed by Autologous Stem Cell Rescue: A Phase I Trial in Advanced Breast Cancer

OBJECTIVES: I. Determine the maximum tolerated dose of paclitaxel when combined with high dose cyclophosphamide and thiotepa followed by autologous peripheral blood stem cell transplantation and radiotherapy in patients with advanced breast cancer. II. Assess the overall safety and toxicity of this regimen in these patients.

OUTLINE: This is a dose escalation study of paclitaxel. Mobilization and harvest: Patients undergo mobilization of peripheral blood stem cells (PBSC) according to the protocol currently used or patients may be mobilized using cytokines alone or chemomobilization at the discretion of the attending physician. PBSC are harvested and selected for CD34+ cells. If an adequate number of CD34+ cells are not harvested, autologous bone marrow may be used. Preparative regimen: Patients receive paclitaxel IV over 24 hours on day -5 and high dose thiotepa IV over 2 hours and high dose cyclophosphamide IV over 2 hours on day -6, day -4 following paclitaxel infusion, and day -2. Cohorts of 3-6 patients receive escalating doses of paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose limiting toxicity. Transplantation: PBSC are reinfused on day 0 or a minimum of 48 hours after completion of chemotherapy. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 0 and continuing until 3 days after blood counts have recovered. Sites of pretransplantation metastases greater than 3 cm are irradiated beginning after PBSC transplantation and after blood counts recover. Patients are followed every month for 1 year, then every 3 months thereafter.

PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study within 1 year.