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.
Primary Purpose: Treatment
Jane N. Winter, MD
Robert H. Lurie Cancer Center
United States: Federal Government
|Robert H. Lurie Comprehensive Cancer Center, Northwestern University||Chicago, Illinois 60611|