title: Induction, mobilization of peripheral blood stem cells (PBSC), high-dose chemotherapy and PBSC infusion in patients with untreated stage IV breast cancer: outcomes by intent to treat analyses.
abstract: We investigated the outcomes of patients with breast cancer undergoing induction chemotherapy, mobilization of peripheral blood stem cells (PBSC) and high-dose chemotherapy (HDC) with PBSC infusion. One hundred and fourteen patients with untreated stage IV breast cancer, with a median age of 46 years (range 24-62), were entered on a phase II trial consisting of; (1) doxorubicin, 5-flurouracil, methotrexate (AFM) x 4 courses at 2 week intervals; (2) cyclophosphamide (4 g/m2), etoposide (600 mg/m2), cisplatin (105 mg/m2) (CEP), filgrastim (6 micrograms/kg/day) and PBSC collection; (3) cyclophosphamide (6 g/m2), thiotepa (500 mg/m2), carboplatin (800 mg/m2), (CTCb) followed by PBSC infusion. All patients received AFM, 107 (94%) received CEP, 93 (82%) received CTCb and PBSC as per protocol and 99 (87%) ultimately received HDC and PBSC. There was one infectious death after AFM and all other deaths were associated with progressive disease. Fifty-two patients (46%) are alive, 21 (18%) without progression, at a median 31 months (range 22-47). The probabilities of survival and progression-free survival at 3.5 years were 0.40 and 0.17, respectively. All 62 patients with visceral disease and/or a prior history of doxorubicin adjuvant therapy have relapsed or progressed. We conclude that the sequential administration of AFM, CEP and CTCb followed by PBSC resulted in long-term PFS only in patients who were NED, had bone-only disease or had lymph node or soft tissue disease with or without bone disease. Other strategies, aimed at improving responses to initial therapy, improving HDC regimens and/or developing immunomodulatory therapies, will be necessary to improve PFS for patients who fail doxorubicin adjuvant or who have visceral disease.
authors.affiliation: Clinical Research Division of Response Oncology, Inc., Memphis, TN, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Weaver
authors.forename: W H
authors.initials: WH
authors.lastname: West
authors.forename: L S
authors.initials: LS
authors.lastname: Schwartzberg
authors.forename: T
authors.initials: T
authors.lastname: Alberico
authors.forename: R
authors.initials: R
authors.lastname: Leff
authors.forename: F A
authors.initials: FA
authors.lastname: Greco
authors.forename: J
authors.initials: J
authors.lastname: Hainsworth
authors.forename: R
authors.initials: R
authors.lastname: Birch
authors.forename: B
authors.initials: B
authors.lastname: McAneny
authors.forename: M
authors.initials: M
authors.lastname: Magee
authors.forename: E
authors.initials: E
authors.lastname: Raefsky
authors.forename: L
authors.initials: L
authors.lastname: Kalman
authors.forename: C D
authors.initials: CD
authors.lastname: Buckner
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D016896:Treatment Outcome