Randomized trial of single compared with tandem high-dose chemotherapy followed by autologous stem-cell transplantation in patients with chemotherapy-sensitive metastatic breast cancer.
OBJECTIVE
To compare progression-free survival between single and tandem high-dose chemotherapy (HDT) followed by autologous stem-cell transplantation in chemotherapy-sensitive metastatic breast cancer patients.


METHODS
Between February 1997 and June 2001, 187 patients with complete and partial remission were randomly assigned to receive either one or two cycles of HDT, consisting of thiotepa (125 mg/m2/d for 4 days), cyclophosphamide (1,500 mg/m2/d for 4 days), and carboplatin (200 mg/m2/d for 4 days), followed by autologous stem-cell transplantation.


RESULTS
One hundred seventy one of 187 randomly assigned patients completed first HDT, but only 52 of 85 completed the second HDT cycle in the tandem HDT arm. The rate of complete remission on an intent-to-treat-basis was 33% in the single-dose HDT arm and 37% in the tandem HDT arm (P = .48). The median progression-free survival times in single and tandem HDT arms were 9.4 and 11.2 months, respectively (one-sided P = .06; two one-sided P = .12), whereas median overall survival time tended to be greater after single versus tandem HDT (29 v 23.5 months, respectively; P = .4). In a multivariate analysis for progression-free survival, tandem HDT (hazard ratio [HR] = 0.71; 95% CI, 0.52 to 0.98; P = .03) and achievement of complete remission after induction chemotherapy (HR = 0.59; 95% CI, 0.37 to 0.96; P = .03) were factors for a better progression-free survival, whereas the factor of three or more sites of metastases (HR = 1.66; 95% CI, 1.12 to 2.47; P = .01) was associated with a worse progression-free survival.


CONCLUSIONS
Despite a trend of improved progression-free survival, tandem HDT cannot be recommended for patients with chemotherapy-sensitive metastatic breast cancer because of a trend for shorter overall survival and higher toxicity compared with single HDT.
Kröger
Nicolaus
N
Bone Marrow Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany. nkroeger@uke.uni-hamburg.de
Frick
Markus
M
Gluz
Oleg
O
Mohrmann
Svjetlana
S
Metzner
Bernd
B
Jackisch
Christian
C
Ko
Yon
Y
Lindemann
Hans-Walter
HW
Meier
Carl Richard
CR
Lohrmann
Hans Peter
HP
Ruffert
Ute
U
Hänel
Matthias
M
Bodenstein
Heinrich
H
Neubauer
Andreas
A
Ehninger
Gerhard
G
Wolf
Hans-Heinrich
HH
Kolbe
Kathrin
K
Burock
Karin
K
Zander
Axel R
AR
Nitz
Ulrike
U
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D016190:Carboplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D016019:Survival Analysis; D013852:Thiotepa / Q000008:administration & dosage; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D003520:Cyclophosphamide; D013852:Thiotepa; D016190:Carboplatin