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

For patients with metastatic breast cancer (MBC) who undergo high-dose ther apy with autologous peripheral blood progenitor cell (PBPC) transplantation , an important prerequisite is a mobilization regimen that efficiently mobi lizes PBPCs while producing an effective anti-tumor effect. We prospectivel y evaluated ifosfamide-based chemotherapy for mobilization efficiency, toxi city and disease response in 37 patients. Patients received two cycles of t he ifosfamide-based regimen; ifosfamide (5 g/m(2) with conventional-dose cy cle and 6 g/m(2) with mobilization cycle) with either 50 mg/m(2) doxorubici n (if limited prior anthracycline and/or progression more than 12 months af ter an anthracycline-based regimen) or 175 mg/m(2) paclitaxel, For the mobi lization cycle, all patients received additional G-CSF (10 mu g/kg SC, dail y) commencing 24 h after completion of chemotherapy, The target yield was > 6 x 10(6) CD34(+) cells/kg, sufficient to support the subsequent three cycl es of high-dose therapy, The mobilization therapy was well tolerated and th e peak days for peripheral blood (PB) CD34(+) cells were days 10-13 with no significant differences in the PB CD34(+) cells mobilization kinetics betw een the ifosfamide-doxorubicin vs ifosfamide-paclitaxel regimens. The media n PBPC CD34(+) cell content ranged from 2.9 to 4.0 x 10(6)/kg per day durin g days 9-14, After a median of 3 (range 1-5) collection days, the median to tal CD34(+) cell, CFU-GM and MNC for all 44 individual sets of collections was 9.2 x 10(6)/kg (range 0.16-54.9), 37 x 10(4)/kg (range 5.7-247) and 7.3 x 10(8)/kg (range 2.1-26.1), respectively, The PBPC target yield was achie ved in 35 of the 37 patients. The overall response rate for the 31 evaluabl e patients was 68% with 10% having progressive disease. Thirty-three patien ts have subsequently received high-dose therapy consisting of three planned cycles of high-dose ifosfamide, thiotepa and paclitaxel with each cycle su pported with PBPCs. Rapid neutrophil and platelet recovery has been observe d, Ifosfamide with G-CSF in combination with doxorubicin or paclitaxel achi eves effective mobilization of PBPC and anti-tumor activity with minimal to xicity.