title: Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer.
abstract: OBJECTIVE
  This randomized phase III trial compared the efficacy and safety of capecitabine with or without bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane.
  
  
  METHODS
  Patients were randomly assigned to receive capecitabine (2,500 mg/m2/d) twice daily on day 1 through 14 every 3 weeks, alone or in combination with bevacizumab (15 mg/kg) on day 1. The primary end point was progression-free survival (PFS), as determined by an independent review facility.
  
  
  RESULTS
  From November 2000 to March 2002, 462 patients were enrolled. Treatment arms were balanced. No significant differences were found in the incidence of diarrhea, hand-foot syndrome, thromboembolic events, or serious bleeding episodes between treatment groups. Of other grade 3 or 4 adverse events, only hypertension requiring treatment (17.9% v 0.5%) was more frequent in patients receiving bevacizumab. Combination therapy significantly increased the response rates (19.8% v 9.1%; P = .001); however, this did not result in a longer PFS (4.86 v 4.17 months; hazard ratio = 0.98). Overall survival (15.1 v 14.5 months) and time to deterioration in quality of life as measured by the Functional Assessment Of Cancer Treatment--Breast were comparable in both treatment groups.
  
  
  CONCLUSIONS
  Bevacizumab was well tolerated in this heavily pretreated patient population. Although the addition of bevacizumab to capecitabine produced a significant increase in response rates, this did not translate into improved PFS or overall survival.
authors.affiliation: Indiana University, Indianapolis, IN, USA. kathmill@iupui.edu
authors.forename: Kathy D
authors.initials: KD
authors.lastname: Miller
authors.forename: Linnea I
authors.initials: LI
authors.lastname: Chap
authors.forename: Frankie A
authors.initials: FA
authors.lastname: Holmes
authors.forename: Melody A
authors.initials: MA
authors.lastname: Cobleigh
authors.forename: P Kelly
authors.initials: PK
authors.lastname: Marcom
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: Maura
authors.initials: M
authors.lastname: Dickler
authors.forename: Beth A
authors.initials: BA
authors.lastname: Overmoyer
authors.forename: James D
authors.initials: JD
authors.lastname: Reimann
authors.forename: Amy P
authors.initials: AP
authors.lastname: Sing
authors.forename: Virginia
authors.initials: V
authors.lastname: Langmuir
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011788:Quality of Life
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil