title: Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment.
abstract: OBJECTIVE
  Effective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with capecitabine in this setting. This study was designed to compare ixabepilone plus capecitabine versus capecitabine alone in anthracycline-pretreated or -resistant and taxane-resistant locally advanced or metastatic breast cancer.
  
  
  METHODS
  Seven hundred fifty-two patients were randomly assigned to ixabepilone 40 mg/m(2) intravenously on day 1 of a 21-day cycle plus capecitabine 2,000 mg/m(2) orally on days 1 through 14 of a 21-day cycle, or capecitabine alone 2,500 mg/m(2) on the same schedule, in this international phase III study. The primary end point was progression-free survival evaluated by blinded independent review.
  
  
  RESULTS
  Ixabepilone plus capecitabine prolonged progression-free survival relative to capecitabine (median, 5.8 v 4.2 months), with a 25% reduction in the estimated risk of disease progression (hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P = .0003). Objective response rate was also increased (35% v 14%; P < .0001). Grade 3/4 treatment-related sensory neuropathy (21% v 0%), fatigue (9% v 3%), and neutropenia (68% v 11%) were more frequent with combination therapy, as was the rate of death as a result of toxicity (3% v 1%, with patients with liver dysfunction [>/= grade 2 liver function tests] at greater risk). Capecitabine-related toxicities were similar for both treatment groups.
  
  
  CONCLUSIONS
  Ixabepilone plus capecitabine demonstrates superior efficacy to capecitabine alone in patients with metastatic breast cancer pretreated or resistant to anthracyclines and resistant to taxanes.
authors.affiliation: M.D. Anderson Cancer Center, Houston, TX, USA. eva.s.thomas@kp.org
authors.forename: Eva S
authors.initials: ES
authors.lastname: Thomas
authors.forename: Henry L
authors.initials: HL
authors.lastname: Gomez
authors.forename: Rubi K
authors.initials: RK
authors.lastname: Li
authors.forename: Hyun-Cheol
authors.initials: HC
authors.lastname: Chung
authors.forename: Luis E
authors.initials: LE
authors.lastname: Fein
authors.forename: Valorie F
authors.initials: VF
authors.lastname: Chan
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.forename: Xavier B
authors.initials: XB
authors.lastname: Pivot
authors.forename: Judith V
authors.initials: JV
authors.lastname: Klimovsky
authors.forename: Fernando Hurtado
authors.initials: FH
authors.lastname: de Mendoza
authors.forename: Binghe
authors.initials: B
authors.lastname: Xu
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.forename: Guillermo L
authors.initials: GL
authors.lastname: Lerzo
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Peck
authors.forename: Pralay
authors.initials: P
authors.lastname: Mukhopadhyay
authors.forename: Linda T
authors.initials: LT
authors.lastname: Vahdat
authors.forename: Henri H
authors.initials: HH
authors.lastname: Roché
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D034261:Epothilones / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D043823:Taxoids / Q000627:therapeutic use
chemical_list: D018943:Anthracyclines; D001952:Bridged-Ring Compounds; D034261:Epothilones; D043823:Taxoids; D003841:Deoxycytidine; C080625:taxane; D000069287:Capecitabine; C430592:ixabepilone; D005472:Fluorouracil