title: Up-front tandem high-dose chemotherapy compared with standard chemotherapy with doxorubicin and paclitaxel in metastatic breast cancer: results of a randomized trial.
abstract: OBJECTIVE
  The role of high-dose chemotherapy (HDCT) in metastatic breast cancer remains controversial. Trials with late intensification HDCT have failed to show an advantage in overall survival. This study was initiated to compare up-front tandem HDCT and standard combination therapy in patients with metastatic breast cancer.
  
  
  METHODS
  Patients without prior chemotherapy for metastatic disease were randomly assigned to standard combination therapy with doxorubicin and paclitaxel (AT) or double HDCT with cyclophosphamide, mitoxantrone, and etoposide followed by peripheral-blood stem-cell transplantation. HDCT was repeated after 6 weeks. Patients were stratified by menopausal and hormone-receptor status. The primary objective was to compare complete response (CR) rates.
  
  
  RESULTS
  A total of 93 patients were enrolled onto the trial. Intent-to-treat CR rates for patients randomized to HDCT and AT were 12.5% and 11.1%, respectively (P = .84). Objective response rates were 66.7% for patients in the high-dose group and 64.4% for patients in the AT arm (P = .82). In an intent-to-treat analysis, there were no significant differences between the two treatments in median time to progression (HDCT, 11.1 months; AT, 10.6 months; P = .67), duration of response (HDCT, 13.9 months; AT, 14.3 months; P = .98), and overall survival (HDCT, 26.9 months; AT, 23.4 months; P = .60). HDCT was associated with significantly more myelosuppression, infection, diarrhea, stomatitis, and nausea and vomiting, whereas patients treated with AT developed more neurotoxicity.
  
  
  CONCLUSIONS
  This trial failed to show a benefit for up-front tandem HDCT compared with standard combination therapy. HDCT was associated with more acute adverse effects.
authors.affiliation: Department of Oncology and Hematology, Charité Campus Mitte, Humboldt University Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany. peter.schmid@charite.de
authors.forename: Peter
authors.initials: P
authors.lastname: Schmid
authors.forename: Walter
authors.initials: W
authors.lastname: Schippinger
authors.forename: Thorsten
authors.initials: T
authors.lastname: Nitsch
authors.forename: Gerdt
authors.initials: G
authors.lastname: Huebner
authors.forename: Volker
authors.initials: V
authors.lastname: Heilmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schultze
authors.forename: Hubert
authors.initials: H
authors.lastname: Hausmaninger
authors.forename: Manfred
authors.initials: M
authors.lastname: Wischnewsky
authors.forename: Kurt
authors.initials: K
authors.lastname: Possinger
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage; D036102:Peripheral Blood Stem Cell Transplantation; D011788:Quality of Life; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D008942:Mitoxantrone; D017239:Paclitaxel