title: Randomized phase II non-inferiority study (NO16853) of two different doses of capecitabine in combination with docetaxel for locally advanced/metastatic breast cancer.
abstract: BACKGROUND
  This phase II study investigated whether a lower-than-approved dose of capecitabine, plus docetaxel (XT), would improve tolerability versus standard-dose XT without compromising efficacy.
  
  
  METHODS
  Women aged ≥18 years with locally advanced/metastatic breast cancer resistant to anthracycline-based chemotherapy in the (neo)adjuvant, first- or second-line metastatic setting were eligible. Patients were randomly assigned to receive standard-dose XT (capecitabine 1250 mg/m(2) twice daily, days 1-14; docetaxel 75 mg/m(2), day 1 every 3 weeks) or low-dose XT (capecitabine 825 mg/m(2) twice daily, days 1-14; docetaxel as above). The primary objective was to demonstrate non-inferiority of low-dose to standard-dose XT in terms of progression-free survival (PFS).
  
  
  RESULTS
  470 patients were randomly allocated in a 1 : 1 ratio to standard-dose or low-dose XT. Median PFS was 7.9 versus 5.8 months [hazard ratio 1.16, 95% confidence interval (CI) 0.95-1.43] in the standard-dose and low-dose arms, respectively. The upper limit of the 95% CI was above the predefined non-inferiority margin (1.35, P = 0.078). Secondary efficacy end points were consistent with PFS. The frequency and severity of adverse events was similar in both treatment arms.
  
  
  CONCLUSIONS
  Non-inferiority of low-dose to standard-dose XT in terms of PFS was not demonstrated; this may be due to regional subgroup effects.
authors.affiliation: Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: abuzdar@mdanderson.org.
authors.forename: A U
authors.initials: AU
authors.lastname: Buzdar
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, Nizam's Institute of Medical Sciences, Hyderabad, India.
authors.forename: R
authors.initials: R
authors.lastname: Digumarti
authors.affiliation: Department of Oncotherapy, National Hospital, Bloemfontein, South Africa.
authors.forename: L
authors.initials: L
authors.lastname: Goedhals
authors.affiliation: Cancer Hospital, Fudan University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.affiliation: Breast Cancer Department, NN Petrov Research Institute of Oncology, St Petersburg, Russia.
authors.forename: V
authors.initials: V
authors.lastname: Semiglazov
authors.affiliation: Department of Oncology, Regional Clinical Oncology Hospital, Yaroslavl, Russia.
authors.forename: S
authors.initials: S
authors.lastname: Cheporov
authors.affiliation: Department of Oncology, Regional Oncology Dispensary, Ivanovo, Russia.
authors.forename: E
authors.initials: E
authors.lastname: Gotovkin
authors.affiliation: Department of Statistics, Dr Manfred Köhler GmbH, Freiburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hoersch
authors.affiliation: Product Development Oncology Department, Hoffmann-La Roche Inc, Nutley, USA.
authors.forename: K
authors.initials: K
authors.lastname: Rittweger
authors.affiliation: Department of Medical Oncology, East and North Hertfordshire NHS Trust, Mount Vernon Cancer Centre, Middlesex, UK.
authors.forename: D W
authors.initials: DW
authors.lastname: Miles
authors.affiliation: Department of Medical Oncology, Baylor-Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, USA.
authors.forename: J
authors.initials: J
authors.lastname: O'Shaughnessy
authors.affiliation: Department of Clinical Pharmacology and Chemotherapy, Blokhin Cancer Research Center, Moscow, Russia.
authors.forename: S
authors.initials: S
authors.lastname: Tjulandin
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D005472:Fluorouracil