Repetitive high-dose therapy with cyclophosphamide, thiotepa and docetaxelwith peripheral blood progenitor cell and filgrastim support for metastatic and locally advanced breast cancer: results of a phase I study

This phase I study was designed to determine the optimal dosages of a novel repetitive high-dose therapy regimen for patients with metastatic breast c ancer (MBC), The planned treatment was three cycles of high-dose cyclophosp hamide, thiotepa and docetaxel delivered every 35 days with progressive dos e-escalation in successive cohorts. Each cycle was supported by peripheral blood progenitor cells (PBPC) and filgrastim, Eighteen patients were entere d into this trial. Of the planned 54 treatment cycles, 44 were delivered an d 11 patients completed all three cycles. The dose-limiting toxicities were interstitial pneumonitis and mucositis,vith moderately severe diarrhea (n = 3) and rash (n = 3), There were no treatment-related deaths. Of the 17 pa tients with evaluable disease, 16 patients responded with six patients achi eving a complete remission and an additional four patients achieving no det ectable disease (negative restaging including PET scan) but a persistently abnormal bone scan, At a median follow-up of 12 months, median progression- free survival was 11 months with the median overall survival not reached, T he recommended doses for phase II/III studies are cyclophosphamide (4 g/m(2 )), thiotepa (300 mg/m(2)) and docetaxel (100 mg/m(2)).