Bone Marrow Transplantation, (1999) 23 , 427–435  1999 Stockton Press All rights reserved 0268–3369/99 $12.00 http:/ / www.stockton-press.co.uk/ bmt 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 HM Prince 1 , J Gardyn 1 , MJ Millward 1 , D Rischin 1 , P Francis 1 , P Gates 1 , P Chapple 1 , M Quinn 1 , S Juneja 1 , M Wolf 1 , EH Januszewicz 1 , G Richardson 2 , J Scarlett 2 , P Briggs 2 , M Brettell 1 and GC Toner 1 1 Blood and Marrow Transplant Service, Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute; and 2 Department of Medical Oncology and Clinical Haematology, Monash Medical Centre, Melbourne, Victoria, Australia Summary: 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 ifosfam- ide-based chemotherapy for mobilization efficiency, tox- icity and disease response in 37 patients. Patients received two cycles of the ifosfamide-based regimen; ifosfamide (5 g/m 2 with conventional-dose cycle and 6 g/m 2 with mobilization cycle) with either 50 mg/m 2 doxorubicin (if limited prior anthracycline and/or pro- gression more than 12 months after an anthracycline- based regimen) or 175 mg/m 2 paclitaxel. For the mobil- ization cycle, all patients received additional G-CSF (10 g/kg SC, daily) commencing 24 h after completion of chemotherapy. The target yield was 6 × 10 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 differ- ences in the PB CD34 + cells mobilization kinetics between the ifosfamide-doxorubicin vs ifosfamide-pacli- taxel regimens. The median PBPC CD34 + cell content ranged from 2.9 to 4.0 × 10 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 9.2 × 10 6 /kg (range 0.16–54.9), 37 × 10 4 /kg (range 5.7–247) and 7.3 × 10 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 ifosfam- ide, thiotepa and paclitaxel with each cycle supported Correspondence: Dr HM Prince, Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, Locked Bag 1, A’Beckett St, Melbourne 3000, Victoria, Australia Received 22 May 1998; accepted 16 October 1998 with PBPCs. Rapid neutrophil and platelet recovery has been observed. Ifosfamide with G-CSF in combination with doxorubicin or paclitaxel achieves effective mobil- ization of PBPC and anti-tumor activity with minimal toxicity. Keywords: ifosfamide; paclitaxel; doxorubicin; mobiliz- ation; stem cells The value of dose-intensive chemotherapy in metastatic breast cancer (MBC) continues to be debated 1–4 and high- dose chemotherapy with autologous bone marrow (ABM) or peripheral blood progenitor cell (PBPC) transplantation continues to be investigated. 5 A single small randomized study examining the outcome of patients with MBC treated with high-dose chemotherapy and ABM or PBPC support demonstrated superior response rates, complete responses (CR) and overall survival (OS) for patients treated in the high-dose arm. 6 Furthermore, in heavily pre-treated patients, CR rates of 20–64% have been reported using a single cycle of high-dose chemotherapy with PBPC trans- plantation. 7 Despite these promising results, only a minority (approximately 10–25%) of these highly selected groups of women with MBC experience prolonged progression-free survival following high-dose therapy. 5 We were therefore interested in examining the toler- ability and efficacy of a novel approach utilizing repetitive high-dose combination chemotherapy for patients with MBC. We initiated a phase I/II study in heavily pre-treated patients with MBC using three cycles of high-dose ifosfam- ide, thiotepa and paclitaxel, with each cycle supported by PBPCs. An important prerequisite for this therapy, was a reliable method of obtaining sufficient PBPCs to ensure rapid and durable engraftment. Furthermore, an effective mobilization regimen needed not only to mobilize adequate PBPCs, but also potentially achieve an anti-tumor effect to maintain patients in at least a stable disease state at the time of commencing the high-dose phase of therapy. We selected ifosfamide as the ‘back-bone’ for our mobil- ization regimen for a number of reasons. Firstly, ifosfamide can be incorporated into chemotherapy regimens to mobil- ize PBPCs. 8–14 Secondly, ifosfamide has some potential