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.
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).
Prince
H M
HM
Blood and Marrow Transplant Service, Peter MacCallum Cancer Institute, Melbourne, Victoria, Australia. mprince@petermac.unimelb.edu.au
Millward
M J
MJ
Rischin
D
D
Blakey
D
D
Francis
P
P
Gates
P
P
Chapple
P
P
Quinn
M
M
Juneja
S
S
Wolf
M
M
Januszewicz
E H
EH
Seymour
J F
JF
Brettell
M
M
Strickland
A
A
Zalcberg
J
J
Richardson
G
G
Scarlett
J
J
Briggs
P
P
Toner
G C
GC
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
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D013852:Thiotepa; D017239:Paclitaxel; D000069585:Filgrastim; D007069:Ifosfamide