title: Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma.
abstract: BACKGROUND
  Uncontrolled studies have reported encouraging outcomes for patients with high-risk primary breast cancer treated with high-dose chemotherapy and autologous hematopoietic stem cell support. We conducted a prospective randomized trial to compare standard-dose chemotherapy with the same therapy followed by high-dose chemotherapy.
  
  
  METHODS
  Patients with 10 or more positive axillary lymph nodes after primary breast surgery or patients with four or more positive lymph nodes after four cycles of primary (neoadjuvant) chemotherapy were eligible. All patients were to receive eight cycles of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). Patients were stratified by stage and randomly assigned to receive two cycles of high-dose cyclophosphamide, etoposide, and cisplatin with autologous hematopoietic stem cell support or no additional chemotherapy. Tamoxifen was planned for postmenopausal patients with estrogen receptor-positive tumors and chest wall radiotherapy was planned for all. All P values are from two-sided tests.
  
  
  RESULTS
  Seventy-eight patients (48 after primary surgery and 30 after primary chemotherapy) were registered. Thirty-nine patients were randomly assigned to FAC and 39 to FAC followed by high-dose chemotherapy. After a median follow-up of 6.5 years, there have been 41 relapses. In intention-to-treat analyses, estimated 3-year relapse-free survival rates were 62% and 48% for FAC and FAC/high-dose chemotherapy, respectively (P =.35), and 3-year survival rates were 77% and 58%, respectively (P =.23). Overall, there was greater and more frequent morbidity associated with high-dose chemotherapy than with FAC; there was one septic death associated with high-dose chemotherapy.
  
  
  CONCLUSIONS
  No relapse-free or overall survival advantage was associated with the use of high-dose chemotherapy, and morbidity was increased with its use. Thus, high-dose chemotherapy is not indicated outside a clinical trial.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. ghortoba@notes.mdacc.tmc.edu
authors.forename: G N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: A U
authors.initials: AU
authors.lastname: Buzdar
authors.forename: R L
authors.initials: RL
authors.lastname: Theriault
authors.forename: V
authors.initials: V
authors.lastname: Valero
authors.forename: D
authors.initials: D
authors.lastname: Frye
authors.forename: D J
authors.initials: DJ
authors.lastname: Booser
authors.forename: F A
authors.initials: FA
authors.lastname: Holmes
authors.forename: S
authors.initials: S
authors.lastname: Giralt
authors.forename: I
authors.initials: I
authors.lastname: Khouri
authors.forename: B
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authors.lastname: Andersson
authors.forename: J L
authors.initials: JL
authors.lastname: Gajewski
authors.forename: G
authors.initials: G
authors.lastname: Rondon
authors.forename: T L
authors.initials: TL
authors.lastname: Smith
authors.forename: S E
authors.initials: SE
authors.lastname: Singletary
authors.forename: F C
authors.initials: FC
authors.lastname: Ames
authors.forename: N
authors.initials: N
authors.lastname: Sneige
authors.forename: E A
authors.initials: EA
authors.lastname: Strom
authors.forename: M D
authors.initials: MD
authors.lastname: McNeese
authors.forename: A B
authors.initials: AB
authors.lastname: Deisseroth
authors.forename: R E
authors.initials: RE
authors.lastname: Champlin
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil