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  • Title: Ifosfamide in combination with paclitaxel or doxorubicin: regimens which effectively mobilize peripheral blood progenitor cells while demonstrating anti-tumor activity in patients with metastatic breast cancer.
    Author: Prince HM, Gardyn J, Millward MJ, Rischin D, Francis P, Gates P, Chapple P, Quinn M, Juneja S, Wolf M, Januszewicz EH, Richardson G, Scarlett J, Briggs P, Brettell M, Toner GC.
    Journal: Bone Marrow Transplant; 1999 Mar; 23(5):427-35. PubMed ID: 10100555.
    Abstract:
    For patients with metastatic breast cancer (MBC) who undergo high-dose therapy with autologous peripheral blood progenitor cell (PBPC) transplantation, an important prerequisite is a mobilization regimen that efficiently mobilizes PBPCs while producing an effective anti-tumor effect. We prospectively evaluated ifosfamide-based chemotherapy for mobilization efficiency, toxicity and disease response in 37 patients. Patients received two cycles of the ifosfamide-based regimen; ifosfamide (5 g/m2 with conventional-dose cycle and 6 g/m2 with mobilization cycle) with either 50 mg/m2 doxorubicin (if limited prior anthracycline and/or progression more than 12 months after an anthracycline-based regimen) or 175 mg/m2 paclitaxel. For the mobilization cycle, all patients received additional G-CSF (10 microg/kg SC, daily) commencing 24 h after completion of chemotherapy. The target yield was >6x10(6) CD34+ cells/kg, sufficient to support the subsequent three cycles of high-dose therapy. The mobilization therapy was well tolerated and the peak days for peripheral blood (PB) CD34+ cells were days 10-13 with no significant differences in the PB CD34+ cells mobilization kinetics between the ifosfamide-doxorubicin vs. ifosfamide-paclitaxel regimens. The median PBPC CD34+ cell content ranged from 2.9 to 4.0x10(6)/kg per day during days 9-14. After a median of 3 (range 1-5) collection days, the median total CD34+ cell, CFU-GM and MNC for all 44 individual sets of collections was 9.2x10(6)/kg (range 0.16-54.9), 37x10(4)/kg (range 5.7-247) and 7.3x10(8)/kg (range 2.1-26.1), respectively. The PBPC target yield was achieved in 35 of the 37 patients. The overall response rate for the 31 evaluable patients was 68% with 10% having progressive disease. Thirty-three patients have subsequently received high-dose therapy consisting of three planned cycles of high-dose ifosfamide, thiotepa and paclitaxel with each cycle supported with PBPCs. Rapid neutrophil and platelet recovery has been observed. Ifosfamide with G-CSF in combination with doxorubicin or paclitaxel achieves effective mobilization of PBPC and anti-tumor activity with minimal toxicity.
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