title: Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial.
abstract: The randomized phase III JO21095 trial compared the efficacy and safety of low-dose capecitabine plus docetaxel combination therapy (XT) versus single-agent administration of docetaxel in anthracycline-pretreated HER2-negative metastatic breast cancer.
  
  
  
  Patients were randomized to either low-dose XT (capecitabine 825 mg/m2twice daily, days 1-14; docetaxel 60 mg/m2, day 1 every 3 weeks) or docetaxel (70 mg/m2, day 1 every 3 weeks). The primary objective was to demonstrate superior progression-free survival (PFS) with low-dose XT versus single-agent docetaxel. Overall survival (OS) and safety were secondary endpoints.
  
  
  
  In total, 162 patients were treated. Median PFS was 10.5 months with low-dose XT and 9.8 months with single-agent docetaxel (hazard ratio [HR] 0.62 [95% confidence interval (CI) 0.40-0.97]; p = 0.03). The OS HR was 0.89 (95% CI 0.52-1.53; p = 0.68). Grade ≥3 treatment-related toxicities occurred in 74% of XT-treated patients and 76% of docetaxel-treated patients. The main differences in grade ≥3 treatment-related toxicities were hand-foot syndrome (7.3% of XT-treated patients vs 0% receiving docetaxel), fatigue/malaise (2.4 vs 10.0%), and peripheral edema (1.2 vs 7.5%). Dose modifications were required in 100% of low-dose XT and 49% of docetaxel patients. Toxicity-related treatment discontinuations occurred in 18 and 33%, respectively.
  
  
  
  The improved PFS with low-dose XT versus docetaxel alone is consistent with higher-dose XT phase III experience, but the safety profile was more favorable and manageable.
authors.affiliation: Department of Surgery, Kansai Medical University Medical Center, 10-15 Fumizono cho, Moriguchi City, Osaka, 570-8507, Japan. yamamotd@takii.kmu.ac.jp.
authors.forename: Daigo
authors.initials: D
authors.lastname: Yamamoto
authors.affiliation: Department of Breast Oncology, Niigata Cancer Center Hospital, Niigata, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Breast Surgery, Sagara Hospital, Kagoshima, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Rai
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Breast Surgical Oncology, Juntendo University Hospital, Tokyo, Japan.
authors.forename: Mitsue
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.affiliation: Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Masuda
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Oura
authors.affiliation: Department of Breast Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Watanabe
authors.affiliation: Biostatistics Center, Kurume University, Fukuoka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hattori
authors.affiliation: Medical Affairs, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Matsuura
authors.affiliation: Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Kuroi
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000069287:Capecitabine / Q000008:administration & dosage; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011788:Quality of Life; D019233:Retreatment; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D043823:Taxoids; D000077143:Docetaxel; D000069287:Capecitabine
keywords: Anthracycline-pretreated; Capecitabine; Docetaxel; HER2-negative; Metastatic breast cancer