title: High-dose busulfan, melphalan, thiotepa and peripheral blood stem cell infusion for the treatment of metastatic breast cancer.
abstract: The purpose of this study was to determine the outcome of patients with metastatic breast cancer treated with high-dose busulfan (Bu), melphalan (Mel) and thiotepa (TT) followed by peripheral blood stem cell (PBSC) infusion. Fifty-one patients with chemotherapy refractory (n = 32) or responsive (n = 19) metastatic breast cancer received Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC collected after chemotherapy and growth factor (n = 43) or growth factor alone (n = 8). The 100 day treatment-related mortality was 8% including one death from cytomegalovirus pneumonia, one from aspiration pneumonia and two from regimen-related toxicity (RRT). Seven of 28 refractory (25%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft tissue disease with at least improvement in bone lesions (PR*). Fifteen of 51 patients (29%) are alive and progression-free a median of 423 days (range 353-934) after treatment, 5/32 (16%) with refractory disease and 10/19 (53%) with responsive disease. The probabilities of progression-free survival (PFS) at 1.5 years for the patients with refractory (n = 32) and responsive (n = 19) disease were 0.24 and 0.53, respectively. These preliminary data suggest that high-dose Bu/Mel/TT has significant activity in patients with advanced breast cancer and may be superior to some previously published regimens.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
authors.forename: W I
authors.initials: WI
authors.lastname: Bensinger
authors.forename: K S
authors.initials: KS
authors.lastname: Schiffman
authors.forename: L
authors.initials: L
authors.lastname: Holmberg
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: R
authors.initials: R
authors.lastname: Maziarz
authors.forename: P
authors.initials: P
authors.lastname: Montgomery
authors.forename: E
authors.initials: E
authors.lastname: Ellis
authors.forename: S
authors.initials: S
authors.lastname: Rivkin
authors.forename: P
authors.initials: P
authors.lastname: Weiden
authors.forename: K
authors.initials: K
authors.lastname: Lilleby
authors.forename: S
authors.initials: S
authors.lastname: Rowley
authors.forename: S
authors.initials: S
authors.lastname: Petersdorf
authors.forename: J P
authors.initials: JP
authors.lastname: Klarnet
authors.forename: W
authors.initials: W
authors.lastname: Nichols
authors.forename: A
authors.initials: A
authors.lastname: Hertler
authors.forename: R
authors.initials: R
authors.lastname: McCroskey
authors.forename: C H
authors.initials: CH
authors.lastname: Weaver
authors.forename: C D
authors.initials: CD
authors.lastname: Buckner
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000628:therapy*; D002066:Busulfan / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004351:Drug Resistance; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage; D014182:Transplantation, Autologous
chemical_list: D013852:Thiotepa; D002066:Busulfan; D008558:Melphalan