title: Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22.
abstract: OBJECTIVE
  The National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a randomized trial (B-22) to determine if intensifying but maintaining the total dose of cyclophosphamide (Cytoxan, Bristol-Myers Squibb Oncology, Princeton, NJ) in a doxorubicin (Adriamycin, Pharmacia, Kalamazoo, MI)-cyclophosphamide combination (AC), or if intensifying and increasing the total dose of cyclophosphamide improves the outcome of women with primary breast cancer and positive axillary nodes.
  
  
  METHODS
  Patients (N = 2,305) were randomized to receive either four courses of standard AC therapy (group 1); intensified therapy, in which the same total dose of cyclophosphamide was administered in two courses (group 2); or intensified and increased therapy, in which the total dose of cyclophosphamide was doubled (group 3). The dose and intensity of doxorubicin were similar in all groups. Disease-free survival (DFS) and overall survival were determined using life-table estimates.
  
  
  RESULTS
  There was no significant difference in DFS (P = .30) or overall survival (P = .95) among the groups through 5 years. At 5 years, the DFS of women in group 1 was similar to that of women in group 2 (62% v 60%, respectively; P = .43) and to that of women in group 3 (62% v 64%, respectively; P = .59). The 5-year survival of women in group 1 was similar to that of women in group 2 (78% v 77%, respectively; P = .86) and to that of women in group 3 (78% v 77%, respectively; P = .82). Grade 4 toxicity increased in groups 2 and 3. Failure to note a difference in outcome among the groups was unrelated to either differences in amount and intensity of cyclophosphamide or to dose delays and intervals between courses of therapy.
  
  
  CONCLUSIONS
  Intensifying or intensifying and increasing the total dose of cyclophosphamide failed to significantly improve either DFS or overall survival in any group. It was concluded that, outside of a clinical trial, dose-intensification of cyclophosphamide in an AC combination represents inappropriate therapy for women with primary breast cancer.
authors.forename: B
authors.initials: B
authors.lastname: Fisher
authors.forename: S
authors.initials: S
authors.lastname: Anderson
authors.forename: D L
authors.initials: DL
authors.lastname: Wickerham
authors.forename: A
authors.initials: A
authors.lastname: DeCillis
authors.forename: N
authors.initials: N
authors.lastname: Dimitrov
authors.forename: E
authors.initials: E
authors.lastname: Mamounas
authors.forename: N
authors.initials: N
authors.lastname: Wolmark
authors.forename: R
authors.initials: R
authors.lastname: Pugh
authors.forename: J N
authors.initials: JN
authors.lastname: Atkins
authors.forename: F J
authors.initials: FJ
authors.lastname: Meyers
authors.forename: N
authors.initials: N
authors.lastname: Abramson
authors.forename: J
authors.initials: J
authors.lastname: Wolter
authors.forename: R S
authors.initials: RS
authors.lastname: Bornstein
authors.forename: L
authors.initials: L
authors.lastname: Levy
authors.forename: E H
authors.initials: EH
authors.lastname: Romond
authors.forename: V
authors.initials: V
authors.lastname: Caggiano
authors.forename: M
authors.initials: M
authors.lastname: Grimaldi
authors.forename: P
authors.initials: P
authors.lastname: Jochimsen
authors.forename: P
authors.initials: P
authors.lastname: Deckers
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D017211:Treatment Failure
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide