title: Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance).
abstract: OBJECTIVE
  Optimal adjuvant chemotherapy for early-stage breast cancer balances efficacy and toxicity. We sought to determine whether single-agent paclitaxel (T) was inferior to doxorubicin and cyclophosphamide (AC), when each was administered for four or six cycles of therapy, and whether it offered less toxicity.
  
  
  METHODS
  Patients with operable breast cancer with 0 to 3 positive nodes were enrolled onto the study to address the noninferiority of single-agent T to AC, defined as the one-sided 95% upper-bound CI (UCB) of hazard ratio (HR) of T versus AC less than 1.30 for the primary end point of relapse-free survival (RFS). As a 2 × 2 factorial design, duration of therapy was also addressed and was previously reported.
  
  
  RESULTS
  With 3,871 patients enrolled onto the trial, a median follow-up period of 6.1 years, and 437 RFS events, we achieved an HR of 1.26 (one sided 95% UCB, 1.48; favoring AC does not allow a conclusion of noninferiority of T with AC; UCB > 1.3). With 266 patient deaths, the HR for overall survival (OS) was 1.27 favoring AC (UCB, 1.56). The estimated absolute advantage of AC at 5 years is 3% for RFS (91 v 88%) and 1% for OS (95 v 94%). All nine treatment-related deaths were patients receiving AC and are included in the analyses of both RFS and OS. Hematologic toxicity was more common in patients treated with AC, and neuropathy was more common in patients treated with T.
  
  
  CONCLUSIONS
  This trial did not show noninferiority of T to AC, a conclusion that is unlikely to change with additional events and follow-up. T was less toxic than AC.
authors.affiliation: Lawrence N. Shulman, Harold J. Burstein, Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Donald A. Berry, MD Anderson Cancer Center, Houston, TX; Constance T. Cirrincione, Gretchen Kimmick, Duke University Medical Center, Durham; Hyman Muss, University of North Carolina at Chapel Hill, Chapel Hill, NC; Heather P. Becker, University of Chicago, Chicago, IL; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Ruth O'Regan, Emory University, Atlanta, GA; Silvana Martino, The Angeles Clinic and Research Institute, Los Angeles, CA; Charles L. Shapiro, The James Cancer Center, Ohio State University, Columbus, OH; Charles J. Schneider, Christiana Healthcare Services, Wilmington, DE; Larry Norton, Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY. Lawrence_Shulman@dfci.harvard.edu.
authors.forename: Lawrence N
authors.initials: LN
authors.lastname: Shulman
authors.affiliation: Lawrence N. Shulman, Harold J. Burstein, Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Donald A. Berry, MD Anderson Cancer Center, Houston, TX; Constance T. Cirrincione, Gretchen Kimmick, Duke University Medical Center, Durham; Hyman Muss, University of North Carolina at Chapel Hill, Chapel Hill, NC; Heather P. Becker, University of Chicago, Chicago, IL; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Ruth O'Regan, Emory University, Atlanta, GA; Silvana Martino, The Angeles Clinic and Research Institute, Los Angeles, CA; Charles L. Shapiro, The James Cancer Center, Ohio State University, Columbus, OH; Charles J. Schneider, Christiana Healthcare Services, Wilmington, DE; Larry Norton, Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Berry
authors.affiliation: Lawrence N. Shulman, Harold J. Burstein, Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Donald A. Berry, MD Anderson Cancer Center, Houston, TX; Constance T. Cirrincione, Gretchen Kimmick, Duke University Medical Center, Durham; Hyman Muss, University of North Carolina at Chapel Hill, Chapel Hill, NC; Heather P. Becker, University of Chicago, Chicago, IL; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Ruth O'Regan, Emory University, Atlanta, GA; Silvana Martino, The Angeles Clinic and Research Institute, Los Angeles, CA; Charles L. Shapiro, The James Cancer Center, Ohio State University, Columbus, OH; Charles J. Schneider, Christiana Healthcare Services, Wilmington, DE; Larry Norton, Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Constance T
authors.initials: CT
authors.lastname: Cirrincione
authors.affiliation: Lawrence N. Shulman, Harold J. Burstein, Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Donald A. Berry, MD Anderson Cancer Center, Houston, TX; Constance T. Cirrincione, Gretchen Kimmick, Duke University Medical Center, Durham; Hyman Muss, University of North Carolina at Chapel Hill, Chapel Hill, NC; Heather P. Becker, University of Chicago, Chicago, IL; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Ruth O'Regan, Emory University, Atlanta, GA; Silvana Martino, The Angeles Clinic and Research Institute, Los Angeles, CA; Charles L. Shapiro, The James Cancer Center, Ohio State University, Columbus, OH; Charles J. Schneider, Christiana Healthcare Services, Wilmington, DE; Larry Norton, Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Heather P
authors.initials: HP
authors.lastname: Becker
authors.affiliation: Lawrence N. Shulman, Harold J. Burstein, Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Donald A. Berry, MD Anderson Cancer Center, Houston, TX; Constance T. Cirrincione, Gretchen Kimmick, Duke University Medical Center, Durham; Hyman Muss, University of North Carolina at Chapel Hill, Chapel Hill, NC; Heather P. Becker, University of Chicago, Chicago, IL; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Ruth O'Regan, Emory University, Atlanta, GA; Silvana Martino, The Angeles Clinic and Research Institute, Los Angeles, CA; Charles L. Shapiro, The James Cancer Center, Ohio State University, Columbus, OH; Charles J. Schneider, Christiana Healthcare Services, Wilmington, DE; Larry Norton, Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.affiliation: Lawrence N. Shulman, Harold J. Burstein, Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Donald A. Berry, MD Anderson Cancer Center, Houston, TX; Constance T. Cirrincione, Gretchen Kimmick, Duke University Medical Center, Durham; Hyman Muss, University of North Carolina at Chapel Hill, Chapel Hill, NC; Heather P. Becker, University of Chicago, Chicago, IL; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Ruth O'Regan, Emory University, Atlanta, GA; Silvana Martino, The Angeles Clinic and Research Institute, Los Angeles, CA; Charles L. Shapiro, The James Cancer Center, Ohio State University, Columbus, OH; Charles J. Schneider, Christiana Healthcare Services, Wilmington, DE; Larry Norton, Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Ruth
authors.initials: R
authors.lastname: O'Regan
authors.affiliation: Lawrence N. Shulman, Harold J. Burstein, Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Donald A. Berry, MD Anderson Cancer Center, Houston, TX; Constance T. Cirrincione, Gretchen Kimmick, Duke University Medical Center, Durham; Hyman Muss, University of North Carolina at Chapel Hill, Chapel Hill, NC; Heather P. Becker, University of Chicago, Chicago, IL; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Ruth O'Regan, Emory University, Atlanta, GA; Silvana Martino, The Angeles Clinic and Research Institute, Los Angeles, CA; Charles L. Shapiro, The James Cancer Center, Ohio State University, Columbus, OH; Charles J. Schneider, Christiana Healthcare Services, Wilmington, DE; Larry Norton, Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.affiliation: Lawrence N. Shulman, Harold J. Burstein, Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Donald A. Berry, MD Anderson Cancer Center, Houston, TX; Constance T. Cirrincione, Gretchen Kimmick, Duke University Medical Center, Durham; Hyman Muss, University of North Carolina at Chapel Hill, Chapel Hill, NC; Heather P. Becker, University of Chicago, Chicago, IL; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Ruth O'Regan, Emory University, Atlanta, GA; Silvana Martino, The Angeles Clinic and Research Institute, Los Angeles, CA; Charles L. Shapiro, The James Cancer Center, Ohio State University, Columbus, OH; Charles J. Schneider, Christiana Healthcare Services, Wilmington, DE; Larry Norton, Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Shapiro
authors.affiliation: Lawrence N. Shulman, Harold J. Burstein, Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Donald A. Berry, MD Anderson Cancer Center, Houston, TX; Constance T. Cirrincione, Gretchen Kimmick, Duke University Medical Center, Durham; Hyman Muss, University of North Carolina at Chapel Hill, Chapel Hill, NC; Heather P. Becker, University of Chicago, Chicago, IL; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Ruth O'Regan, Emory University, Atlanta, GA; Silvana Martino, The Angeles Clinic and Research Institute, Los Angeles, CA; Charles L. Shapiro, The James Cancer Center, Ohio State University, Columbus, OH; Charles J. Schneider, Christiana Healthcare Services, Wilmington, DE; Larry Norton, Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Schneider
authors.affiliation: Lawrence N. Shulman, Harold J. Burstein, Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Donald A. Berry, MD Anderson Cancer Center, Houston, TX; Constance T. Cirrincione, Gretchen Kimmick, Duke University Medical Center, Durham; Hyman Muss, University of North Carolina at Chapel Hill, Chapel Hill, NC; Heather P. Becker, University of Chicago, Chicago, IL; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Ruth O'Regan, Emory University, Atlanta, GA; Silvana Martino, The Angeles Clinic and Research Institute, Los Angeles, CA; Charles L. Shapiro, The James Cancer Center, Ohio State University, Columbus, OH; Charles J. Schneider, Christiana Healthcare Services, Wilmington, DE; Larry Norton, Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Kimmick
authors.affiliation: Lawrence N. Shulman, Harold J. Burstein, Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Donald A. Berry, MD Anderson Cancer Center, Houston, TX; Constance T. Cirrincione, Gretchen Kimmick, Duke University Medical Center, Durham; Hyman Muss, University of North Carolina at Chapel Hill, Chapel Hill, NC; Heather P. Becker, University of Chicago, Chicago, IL; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Ruth O'Regan, Emory University, Atlanta, GA; Silvana Martino, The Angeles Clinic and Research Institute, Los Angeles, CA; Charles L. Shapiro, The James Cancer Center, Ohio State University, Columbus, OH; Charles J. Schneider, Christiana Healthcare Services, Wilmington, DE; Larry Norton, Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Burstein
authors.affiliation: Lawrence N. Shulman, Harold J. Burstein, Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Donald A. Berry, MD Anderson Cancer Center, Houston, TX; Constance T. Cirrincione, Gretchen Kimmick, Duke University Medical Center, Durham; Hyman Muss, University of North Carolina at Chapel Hill, Chapel Hill, NC; Heather P. Becker, University of Chicago, Chicago, IL; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Ruth O'Regan, Emory University, Atlanta, GA; Silvana Martino, The Angeles Clinic and Research Institute, Los Angeles, CA; Charles L. Shapiro, The James Cancer Center, Ohio State University, Columbus, OH; Charles J. Schneider, Christiana Healthcare Services, Wilmington, DE; Larry Norton, Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.affiliation: Lawrence N. Shulman, Harold J. Burstein, Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Donald A. Berry, MD Anderson Cancer Center, Houston, TX; Constance T. Cirrincione, Gretchen Kimmick, Duke University Medical Center, Durham; Hyman Muss, University of North Carolina at Chapel Hill, Chapel Hill, NC; Heather P. Becker, University of Chicago, Chicago, IL; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Ruth O'Regan, Emory University, Atlanta, GA; Silvana Martino, The Angeles Clinic and Research Institute, Los Angeles, CA; Charles L. Shapiro, The James Cancer Center, Ohio State University, Columbus, OH; Charles J. Schneider, Christiana Healthcare Services, Wilmington, DE; Larry Norton, Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Hyman
authors.initials: H
authors.lastname: Muss
authors.affiliation: Lawrence N. Shulman, Harold J. Burstein, Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Donald A. Berry, MD Anderson Cancer Center, Houston, TX; Constance T. Cirrincione, Gretchen Kimmick, Duke University Medical Center, Durham; Hyman Muss, University of North Carolina at Chapel Hill, Chapel Hill, NC; Heather P. Becker, University of Chicago, Chicago, IL; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Ruth O'Regan, Emory University, Atlanta, GA; Silvana Martino, The Angeles Clinic and Research Institute, Los Angeles, CA; Charles L. Shapiro, The James Cancer Center, Ohio State University, Columbus, OH; Charles J. Schneider, Christiana Healthcare Services, Wilmington, DE; Larry Norton, Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.affiliation: Lawrence N. Shulman, Harold J. Burstein, Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Donald A. Berry, MD Anderson Cancer Center, Houston, TX; Constance T. Cirrincione, Gretchen Kimmick, Duke University Medical Center, Durham; Hyman Muss, University of North Carolina at Chapel Hill, Chapel Hill, NC; Heather P. Becker, University of Chicago, Chicago, IL; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Ruth O'Regan, Emory University, Atlanta, GA; Silvana Martino, The Angeles Clinic and Research Institute, Los Angeles, CA; Charles L. Shapiro, The James Cancer Center, Ohio State University, Columbus, OH; Charles J. Schneider, Christiana Healthcare Services, Wilmington, DE; Larry Norton, Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel