title: Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial.
abstract: OBJECTIVE
  Anthracyclines, taxanes, and alkylating agents are among the most active agents in treatment of adjuvant breast cancer (BC), but the optimal schedule for their administration is unknown. We performed an adjuvant trial to compare the sequential regimen of doxorubicin with cyclophosphamide (AC) followed by docetaxel (ie, AC>T) with the combination regimen of TAC.
  
  
  METHODS
  Women with node-positive, human epidermal growth factor receptor 2-nonamplified, operable BC were stratified by number of axillary nodes and hormone receptor status and were randomly assigned to adjuvant chemotherapy with six cycles of TAC (75/50/500 mg/m² every 3 weeks) or four cycles of AC (60/600 mg/m² every 3 weeks) followed by four doses of docetaxel at 100 mg/m² every 3 weeks (AC>T). After completion of chemotherapy, radiation therapy was given as indicated, and patients with hormone receptor (HR) -positive disease received adjuvant hormonal therapy with tamoxifen and/or aromatase inhibitors.
  
  
  RESULTS
  In 30 months, 3,298 patients were enrolled (n = 1,649 in each arm). The major baseline characteristics were well balanced between the groups. At a median follow-up of 65 months, estimated 5-year disease-free survival rates were 79% in both groups (log-rank P = .98; hazard ratio [HR], 1.0; 95%CI, 0.86 to 1.16), and 5-year overall survival rates for both arms were 88% and 89%, respectively (log-rank P = .37; HR, 0.91; 95% CI, 0.75 to 1.11). TAC was associated with more febrile neutropenia and thrombocytopenia, and AC>T was associated with more sensory neuropathy, nail changes, and myalgia. The incidence of neutropenic infection was similar in both groups.
  
  
  CONCLUSIONS
  The sequential and combination regimens incorporating three drugs were equally effective but differed in toxicity profile.
authors.affiliation: Red Cross Clinics, Women's Hospital, München, Germany. w.eiermann@gmx.net
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eiermann
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pienkowski
authors.forename: John
authors.initials: J
authors.lastname: Crown
authors.forename: Saeed
authors.initials: S
authors.lastname: Sadeghi
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin
authors.forename: Arlene
authors.initials: A
authors.lastname: Chan
authors.forename: Mansoor
authors.initials: M
authors.lastname: Saleh
authors.forename: Sandeep
authors.initials: S
authors.lastname: Sehdev
authors.forename: Louise
authors.initials: L
authors.lastname: Provencher
authors.forename: Vladimir
authors.initials: V
authors.lastname: Semiglazov
authors.forename: Michael
authors.initials: M
authors.lastname: Press
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Mary-Ann
authors.initials: MA
authors.lastname: Lindsay
authors.forename: Alessandro
authors.initials: A
authors.lastname: Riva
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
authors.forename: Philippe
authors.initials: P
authors.lastname: Drevot
authors.forename: Henry
authors.initials: H
authors.lastname: Taupin
authors.forename: John R
authors.initials: JR
authors.lastname: Mackey
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide; D066246:ErbB Receptors