title: High-dose chemotherapy with autologous hematopoietic stem-cell transplantation in metastatic breast cancer: overview of six randomized trials.
abstract: OBJECTIVE
  High doses of effective chemotherapy are compelling if they can be delivered safely. Substantial interest in supporting high-dose chemotherapy with bone marrow or autologous hematopoietic stem-cell transplantation in the 1980s and 1990s led to the initiation of randomized trials to evaluate its effect in the treatment of metastatic breast cancer.
  
  
  METHODS
  We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support. We assembled a single database containing individual patient information from these trials. The primary analysis of overall survival was a log-rank test comparing high dose versus control. We also used Cox proportional hazards regression, adjusting for known covariates. We addressed potential treatment differences within subsets of patients.
  
  
  RESULTS
  The effect of high-dose chemotherapy on overall survival was not statistically different (median, 2.16 v 2.02 years; P = .08). A statistically significant advantage in progression-free survival (median, 0.91 v 0.69 years) did not translate into survival benefit. Subset analyses found little evidence that there are groups of patients who might benefit from high-dose chemotherapy with hematopoietic support.
  
  
  CONCLUSIONS
  Overall survival of patients with metastatic breast cancer in the six randomized trials was not significantly improved by high-dose chemotherapy; any benefit from high doses was small. No identifiable subset of patients seems to benefit from high-dose chemotherapy.
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77230-1402, USA. dberry@mdanderson.org
authors.forename: Donald A
authors.initials: DA
authors.lastname: Berry
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.forename: Marcella M
authors.initials: MM
authors.lastname: Johnson
authors.forename: Xiudong
authors.initials: X
authors.lastname: Lei
authors.forename: Jean
authors.initials: J
authors.lastname: Caputo
authors.forename: Dori A
authors.initials: DA
authors.lastname: Smith
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Yancey
authors.forename: Michael
authors.initials: M
authors.lastname: Crump
authors.forename: Edward A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: Pierre
authors.initials: P
authors.lastname: Biron
authors.forename: John P
authors.initials: JP
authors.lastname: Crown
authors.forename: Peter
authors.initials: P
authors.lastname: Schmid
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lotz
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rosti
authors.forename: Marco
authors.initials: M
authors.lastname: Bregni
authors.forename: Taner
authors.initials: T
authors.lastname: Demirer
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D004334:Drug Administration Schedule; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016032:Randomized Controlled Trials as Topic; D011960:Receptors, Estrogen / Q000032:analysis; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D011960:Receptors, Estrogen