title: 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.
abstract: 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.
authors.affiliation: Breast Centre, University Hospital Düsseldorf, Düsseldorf, Germany. nitzu@uni-duesseldorf.de
authors.forename: Ulrike Anneliese
authors.initials: UA
authors.lastname: Nitz
authors.forename: Svjetlana
authors.initials: S
authors.lastname: Mohrmann
authors.forename: Johannes
authors.initials: J
authors.lastname: Fischer
authors.forename: Walter
authors.initials: W
authors.lastname: Lindemann
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.forename: Christoph
authors.initials: C
authors.lastname: Werner
authors.forename: Carsten
authors.initials: C
authors.lastname: Ziske
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kirchner
authors.forename: Bernd
authors.initials: B
authors.lastname: Metzner
authors.forename: Rainer
authors.initials: R
authors.lastname: Souchon
authors.forename: Ute
authors.initials: U
authors.lastname: Ruffert
authors.forename: Gerhart
authors.initials: G
authors.lastname: Schütt
authors.forename: Anke
authors.initials: A
authors.lastname: Pollmanns
authors.forename: Hans Joachim
authors.initials: HJ
authors.lastname: Schmoll
authors.forename: Constantin
authors.initials: C
authors.lastname: Middecke
authors.forename: Jörg
authors.initials: J
authors.lastname: Baltzer
authors.forename: Iris
authors.initials: I
authors.lastname: Schrader
authors.forename: Herrmann
authors.initials: H
authors.lastname: Wiebringhaus
authors.forename: Yon
authors.initials: Y
authors.lastname: Ko
authors.forename: Siegfried
authors.initials: S
authors.lastname: Rösel
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwenzer
authors.forename: Peter
authors.initials: P
authors.lastname: Wernet
authors.forename: Axel
authors.initials: A
authors.lastname: Hinke
authors.forename: Hans Georg
authors.initials: HG
authors.lastname: Bender
authors.forename: Markus
authors.initials: M
authors.lastname: Frick
mesh_terms: 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*