Repetitive high-dose therapy with ifosfamide, thiotepa and paclitaxel withperipheral blood progenitor cell and filgrastim support for metastatic andlocally advanced breast cancer: Results of a phase I study

wBackground: This phase I study was designed to determine the optimal dosag es of a novel repetitive high-dose therapy regimen for patients with metast atic breast cancer (MBC). Patients and methods: The planned treatment was three cycles of high-dose i fosfamide, thiotepa and conventional-dose paclitaxel delivered every 28 day s with progressive dose-escalation in successive cohorts. Each cycle was su pported by peripheral blood progenitor cells (PBPC) and filgrastim. Results: Twenty-three patients were entered into this trial. Of the planned 69 treatment cycles, 59 were delivered and fifteen patients completed all three cycles. The dose-limiting toxicities were renal tubular acidosis, enc ephalopathy, mucositis and enterocolitis. There was one treatment-related h emorrhagic death. Conclusions: The recommended doses for phase II or III studies are ifosfami de (10 g/m(2)), thiotepa (350 mg/m(2)) and paclitaxel (175 mg/m(2)).