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.
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.
Weaver
C H
CH
Clinical Research Division of Response Oncology, Inc., Memphis, TN, USA.
West
W H
WH
Schwartzberg
L S
LS
Alberico
T
T
Leff
R
R
Greco
F A
FA
Hainsworth
J
J
Birch
R
R
McAneny
B
B
Magee
M
M
Raefsky
E
E
Kalman
L
L
Buckner
C D
CD
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