title: Comparison of an AC-taxane versus AC-free regimen and paclitaxel versus docetaxel in patients with lymph node-positive breast cancer: Final results of the National Surgical Adjuvant Study of Breast Cancer 02 trial, a randomized comparative phase 3 study.
abstract: BACKGROUND
  In postoperative patients with breast cancer, the combination of an anthracycline and cyclophosphamide (AC) followed by a taxane is a standard regimen. In the current study, the authors examined whether AC could be safely omitted, and compared the effectiveness of paclitaxel versus docetaxel.
  
  
  METHODS
  Female postoperative patients with axillary lymph node-positive breast cancer were eligible for enrollment in this phase 3, open-label, randomized controlled trial at 84 centers in Japan. Patients were randomized to 4 cycles of doxorubicin at a dose of 60 mg/m2and cyclophosphamide at a dose of 600 mg/m2(AC) followed by 4 cycles of paclitaxel at a dose of 175 mg/m2(ACpT) or AC followed by 4 cycles of docetaxel at a dose of 75 mg/m2(ACdT), or 8 cycles of paclitaxel (PTx) or docetaxel (DTx) every 3 weeks. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival adverse events. The authors adopted a 2 × 2 factorial design to examine the AC containing-regimens (ACpT and ACdT) versus the AC free-regimens (PTx and DTx), and the paclitaxel-containing regimens (ACpT and PTx) versus the docetaxel-containing regimens (ACdT and DTx).
  
  
  RESULTS
  Of 1060 patients, 1049 were treated and included in the intention-to-treat population. The DFS results did not demonstrate noninferiority between the AC-containing and the AC-free regimens (hazard ratio [HR], 1.19; 95% confidence interval [95% CI], 0.982-1.448 [Pnoninferiority= .30]). Better outcomes were noted in patients treated with the docetaxel-containing regimens compared with the paclitaxel-containing regimens with respect to DFS (HR, 0.72; 95% CI, 0.589-0.875 [P = .0008]) and overall survival (HR, 0.75; 95% CI, 0.574-0.980 [P = .035]). Neutropenia, nausea, and vomiting were found to occur more often in the AC-containing arms, whereas the incidence of edema was greater in the docetaxel-containing treatment arms.
  
  
  CONCLUSIONS
  Noninferiority in DFS was not demonstrated between the AC-containing and AC-free regimens. Compared with a similar regimen of paclitaxel, docetaxel appeared to increase the DFS. Cancer 2017;123:759-68. © 2016 American Cancer Society.
authors.affiliation: Department of Medical Oncology, Hamamatsu Oncology Center, Hamamatsu, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Surgery, Yamato Municipal Hospital, Yamato, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kuranami
authors.affiliation: Breast Oncology, Saitama Cancer Center, Kita-Adachi, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Division of Breast Surgery, Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Masuda
authors.affiliation: Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Aogi
authors.affiliation: Breast Oncology Center, Cancer Institute Hospital of the Japanese Foundation of Cancer Research, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.affiliation: Department of Oncology and Hematology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mukai
authors.affiliation: Clinical Research Support Center (CresCent), The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Uemura
authors.affiliation: Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007564:Japan; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D001952:Bridged-Ring Compounds; D043823:Taxoids; D000077143:Docetaxel; C080625:taxane; D003520:Cyclophosphamide; D017239:Paclitaxel
keywords: adjuvant therapy; docetaxel; doxorubicin and cyclophosphamide (AC)-taxane; paclitaxel; randomized phase 3