title: Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Scandinavian Breast Group 9401 study.
abstract: BACKGROUND
  Chemotherapy drug distribution varies greatly among individual patients. Therefore, we developed an individualised fluorouracil, epirubicin, cyclophosphamide (FEC) regimen to improve outcomes in patients with high-risk early breast cancer. We then did a randomised trial to compare this individually tailored FEC regimen with conventional adjuvant chemotherapy followed by consolidation with high-dose chemotherapy with stem-cell support.
  
  
  METHODS
  525 women younger than 60 years of age with high-risk primary breast cancer were randomised after surgery to receive nine cycles of tailored FEC to haematological equitoxicity with granulocyte colony-stimulating factor (G-CSF) support (n=251), or three cycles of FEC at standard doses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb), and peripheral-blood stem-cell or bone-marrow support (n=274). Both groups received locoregional radiation therapy and tamoxifen for 5 years. The primary outcome measure was relapse-free survival, and analysis was by intention to treat.
  
  
  RESULTS
  At a median follow-up of 34.3 months, there were 81 breast-cancer relapses in the tailored FEC group versus 113 in the CTCb group (double triangular method p=0.04). 60 deaths occurred in the tailored FEC group and 82 in the CTCb group (log-rank p=0.12). Patients in the CTCb group experienced more grade 3 or 4 acute toxicity compared with the tailored FEC group (p<0.0001). Two treatment-related deaths (0.7%) occurred in the CTCb group. Six patients in the tailored FEC group developed acute myeloid leukaemia and three developed myelodysplastic syndrome.
  
  
  CONCLUSIONS
  Tailored FEC with G-CSF support resulted in a significantly improved relapse-free survival and fewer grade 3 and 4 toxicities compared with marrow-supported high-dose chemotherapy with CTCb as adjuvant therapy of women with high-risk primary breast cancer.
authors.affiliation: Radiumhemmet, Karolinska Hospital, Stockholm, Sweden. jonas.bergh@cck.ki.se
authors.forename: J
authors.initials: J
authors.lastname: Bergh
authors.forename: T
authors.initials: T
authors.lastname: Wiklund
authors.forename: B
authors.initials: B
authors.lastname: Erikstein
authors.forename: E
authors.initials: E
authors.lastname: Lidbrink
authors.forename: H
authors.initials: H
authors.lastname: Lindman
authors.forename: P
authors.initials: P
authors.lastname: Malmström
authors.forename: P
authors.initials: P
authors.lastname: Kellokumpu-Lehtinen
authors.forename: N O
authors.initials: NO
authors.lastname: Bengtsson
authors.forename: G
authors.initials: G
authors.lastname: Söderlund
authors.forename: G
authors.initials: G
authors.lastname: Anker
authors.forename: E
authors.initials: E
authors.lastname: Wist
authors.forename: S
authors.initials: S
authors.lastname: Ottosson
authors.forename: E
authors.initials: E
authors.lastname: Salminen
authors.forename: P
authors.initials: P
authors.lastname: Ljungman
authors.forename: H
authors.initials: H
authors.lastname: Holte
authors.forename: J
authors.initials: J
authors.lastname: Nilsson
authors.forename: C
authors.initials: C
authors.lastname: Blomqvist
authors.forename: N
authors.initials: N
authors.lastname: Wilking
mesh_terms: D000208:Acute Disease; D000328:Adult; D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007262:Infusions, Intravenous; D007951:Leukemia, Myeloid / Q000139:chemically induced; D008207:Lymphatic Metastasis; D015412:Mastectomy, Segmental; D008875:Middle Aged; D016016:Proportional Hazards Models; D013548:Sweden; D013852:Thiotepa / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D003520:Cyclophosphamide; D013852:Thiotepa; D016190:Carboplatin; D005472:Fluorouracil