Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer

J Clin Oncol. 2006 Dec 1;24(34):5381-7. doi: 10.1200/JCO.2006.06.5391.


Purpose: The combination of doxorubicin and cyclophosphamide (AC) is a standard adjuvant chemotherapy regimen. Studies of docetaxel and cyclophosphamide (TC) in metastatic breast cancer (MBC) showed promise in MBC. In 1997, we initiated a randomized adjuvant trial of TC compared with standard-dose AC with a primary end point of disease-free survival (DFS).

Patients and methods: Patients were eligible if they had stage I to III operable invasive breast cancer with complete surgical excision of the primary tumor. Between June 1997 and December 1999, 1,016 patients were randomly assigned to four cycles of either standard-dose AC (60 and 600 mg/m2, respectively; n = 510) or TC (75 and 600 mg/m2, respectively; n = 506), administered intravenously every 3 weeks as adjuvant chemotherapy. Radiation therapy (as indicated) and tamoxifen, for patients with hormone receptor-positive disease, were administered after completion of chemotherapy.

Results: Both treatment groups (TC and AC) were well balanced with respect to major prognostic factors. Patients were observed through 2005 for a median of 5.5 years. At 5 years, DFS rate was significantly superior for TC compared with AC (86% v 80%, respectively; hazard ratio [HR] = 0.67; 95% CI, 0.50 to 0.94; P = .015). Overall survival rates for TC and AC were 90% and 87%, respectively (HR = 0.76; 95% CI, 0.52 to 1.1; P = .13). More myalgia, arthralgia, edema, and febrile neutropenia occurred on the TC arm; more nausea and vomiting occurred on the AC arm as well as one incident of congestive heart failure.

Conclusion: At 5 years, TC was associated with a superior DFS and a different toxicity profile compared with AC.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Docetaxel
  • Doxorubicin / administration & dosage
  • Female
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Nausea / chemically induced
  • Neoplasm Staging
  • Neutropenia / chemically induced
  • Prospective Studies
  • Survival Rate
  • Taxoids / administration & dosage
  • Vomiting / chemically induced


  • Taxoids
  • Docetaxel
  • Doxorubicin
  • Cyclophosphamide