Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial.
BACKGROUND
Breast cancer with extensive axillary-lymph-node involvement has a poor prognosis after conventional treatment. In trials with historical controls, high-dose chemotherapy produced improved outcomes. We compared an intensive double-cycle high-dose chemotherapy regimen with an accelerated conventionally dosed regimen in high-risk breast cancer in a multicentre trial.


METHODS
Patients with at least nine positive nodes were randomly assigned either two courses of accelerated (2-week intervals, with filgrastim support), conventionally dosed epirubicin and cyclophosphamide followed by two courses of high-dose chemotherapy (epirubicin, cyclophosphamide, and thiotepa supported by peripheral-blood progenitors) or four identical cycles of epirubicin and cyclophosphamide followed by three cycles of accelerated cyclophosphamide, methotrexate, and fluorouracil. The primary endpoint was event-free survival. Analyses were done both by intention to treat and per protocol.


RESULTS
403 patients were enrolled; 201 were assigned high-dose chemotherapy and 202 conventional treatment. The mean number of positive nodes was 17.6, and median follow-up was 48.6 months. 4-year event-free survival (intention-to-treat analysis) was 60% (95% CI 53-67) in the high-dose chemotherapy group and 44% (37-52) in the control group (p=0.00069). The corresponding overall survival was 75% (69-82) versus 70% (64-77; p=0.02). There were no treatment-related deaths.


CONCLUSIONS
Our finding of significant improvements in both event-free and overall survival for high-dose chemotherapy compared with a dose-dense conventional regimen contrasts with the results of other studies. The discrepancy might be due partly to design differences (tandem, brief induction) between our regimen and those studied in other trials. This approach merits further study.
Nitz
Ulrike Anneliese
UA
Breast Centre, University Hospital Düsseldorf, Düsseldorf, Germany. nitzu@uni-duesseldorf.de
Mohrmann
Svjetlana
S
Fischer
Johannes
J
Lindemann
Walter
W
Berdel
Wolfgang E
WE
Jackisch
Christian
C
Werner
Christoph
C
Ziske
Carsten
C
Kirchner
Hartmut
H
Metzner
Bernd
B
Souchon
Rainer
R
Ruffert
Ute
U
Schütt
Gerhart
G
Pollmanns
Anke
A
Schmoll
Hans Joachim
HJ
Middecke
Constantin
C
Baltzer
Jörg
J
Schrader
Iris
I
Wiebringhaus
Herrmann
H
Ko
Yon
Y
Rösel
Siegfried
S
Schwenzer
Thomas
T
Wernet
Peter
P
Hinke
Axel
A
Bender
Hans Georg
HG
Frick
Markus
M
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018592:Cross-Over Studies; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*