title: Repetitive high-dose therapy with ifosfamide, thiotepa and paclitaxel with peripheral blood progenitor cell and filgrastim support for metastatic and locally advanced breast cancer: results of a phase I study.
abstract: BACKGROUND
  This phase I study was designed to determine the optimal dosages of a novel repetitive high-dose therapy regimen for patients with metastatic breast cancer (MBC).
  
  
  METHODS
  The planned treatment was three cycles of high-dose ifosfamide, thiotepa and conventional-dose paclitaxel delivered every 28 days with progressive dose-escalation in successive cohorts. Each cycle was supported 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, encephalopathy, mucositis and enterocolitis. There was one treatment-related hemorrhagic death.
  
  
  CONCLUSIONS
  The recommended doses for phase II or III studies are ifosfamide (10 g/m2), thiotepa (350 mg/m2) and paclitaxel (175 mg/m2).
authors.affiliation: Blood and Marrow Transplant Service, Peter MacCallum Cancer Institute, Melbourne, Victoria, Australia. mprince@petermac.unimelb.edu.au
authors.forename: H M
authors.initials: HM
authors.lastname: Prince
authors.forename: M J
authors.initials: MJ
authors.lastname: Millward
authors.forename: D
authors.initials: D
authors.lastname: Rischin
authors.forename: D
authors.initials: D
authors.lastname: Blakey
authors.forename: P
authors.initials: P
authors.lastname: Francis
authors.forename: P
authors.initials: P
authors.lastname: Gates
authors.forename: P
authors.initials: P
authors.lastname: Chapple
authors.forename: M
authors.initials: M
authors.lastname: Quinn
authors.forename: S
authors.initials: S
authors.lastname: Juneja
authors.forename: M
authors.initials: M
authors.lastname: Wolf
authors.forename: E H
authors.initials: EH
authors.lastname: Januszewicz
authors.forename: J F
authors.initials: JF
authors.lastname: Seymour
authors.forename: M
authors.initials: M
authors.lastname: Brettell
authors.forename: A
authors.initials: A
authors.lastname: Strickland
authors.forename: J
authors.initials: J
authors.lastname: Zalcberg
authors.forename: G
authors.initials: G
authors.lastname: Richardson
authors.forename: J
authors.initials: J
authors.lastname: Scarlett
authors.forename: P
authors.initials: P
authors.lastname: Briggs
authors.forename: G C
authors.initials: GC
authors.lastname: Toner
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001315:Australia; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D011994:Recombinant Proteins; D012720:Severity of Illness Index; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D013852:Thiotepa; D017239:Paclitaxel; D000069585:Filgrastim; D007069:Ifosfamide