title: Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer.
abstract: OBJECTIVE
  This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival.
  
  
  METHODS
  After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m(2), with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m(2), for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m(2). Tamoxifen was given to 94% of patients with hormone receptor-positive tumors.
  
  
  RESULTS
  There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m(2), respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald chi(2) P =.0023; unadjusted Wilcoxon P =.0011) and 18% for death (adjusted P =.0064; unadjusted P =.0098). At 5 years, the disease-free survival (+/- SE) was 65% (+/- 1) and 70% (+/- 1), and overall survival was 77% (+/- 1) and 80% (+/- 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor-negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor-positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest.
  
  
  CONCLUSIONS
  The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.
authors.affiliation: University of California at San Francisco, San, Francisco, CA 94143, USA. craig.henderson@accessoncology.com
authors.forename: I Craig
authors.initials: IC
authors.lastname: Henderson
authors.forename: Donald A
authors.initials: DA
authors.lastname: Berry
authors.forename: George D
authors.initials: GD
authors.lastname: Demetri
authors.forename: Constance T
authors.initials: CT
authors.lastname: Cirrincione
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Goldstein
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.forename: M Robert
authors.initials: MR
authors.lastname: Cooper
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Tkaczuk
authors.forename: Gini
authors.initials: G
authors.lastname: Fleming
authors.forename: James F
authors.initials: JF
authors.lastname: Holland
authors.forename: David B
authors.initials: DB
authors.lastname: Duggan
authors.forename: John T
authors.initials: JT
authors.lastname: Carpenter
authors.forename: Emil
authors.initials: E
authors.lastname: Frei
authors.forename: Richard L
authors.initials: RL
authors.lastname: Schilsky
authors.forename: William C
authors.initials: WC
authors.lastname: Wood
authors.forename: Hyman B
authors.initials: HB
authors.lastname: Muss
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D004317:Doxorubicin; D017239:Paclitaxel