title: Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results.
abstract: OBJECTIVE
  Docetaxel and capecitabine, a tumor-activated oral fluoropyrimidine, show high single-agent efficacy in metastatic breast cancer (MBC) and synergy in preclinical studies. This international phase III trial compared efficacy and tolerability of capecitabine/docetaxel therapy with single-agent docetaxel in anthracycline-pretreated patients with MBC.
  
  
  METHODS
  Patients were randomized to 21-day cycles of oral capecitabine 1,250 mg/m(2) twice daily on days 1 to 14 plus docetaxel 75 mg/m(2) on day 1 (n = 255) or to docetaxel 100 mg/m(2) on day 1 (n = 256).
  
  
  RESULTS
  Capecitabine/docetaxel resulted in significantly superior efficacy in time to disease progression (TTP) (hazard ratio, 0.652; 95% confidence interval [CI], 0.545 to 0.780; P =.0001; median, 6.1 v 4.2 months), overall survival (hazard ratio, 0.775; 95% CI, 0.634 to 0.947; P =.0126; median, 14.5 v 11.5 months), and objective tumor response rate (42% v 30%, P =.006) compared with docetaxel. Gastrointestinal side effects and hand-foot syndrome were more common with combination therapy, whereas myalgia, arthralgia, and neutropenic fever/sepsis were more common with single-agent docetaxel. More grade 3 adverse events occurred with combination therapy (71% v 49%, respectively), whereas grade 4 events were slightly more common with docetaxel (31% v 25% with combination).
  
  
  CONCLUSIONS
  The significantly superior TTP and survival achieved with the addition of capecitabine to docetaxel 75 mg/m(2), with the manageable toxicity profile, indicate that this combination provides clear benefits over single-agent docetaxel 100 mg/m(2). Docetaxel/capecitabine therapy is an important treatment option for women with anthracycline-pretreated MBC.
authors.affiliation: Baylor-Sammons Cancer Center, Dallas, TX 75246, USA. joyce.o'shaughnessey@usoncology.com
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
authors.forename: David
authors.initials: D
authors.lastname: Miles
authors.forename: Svetislava
authors.initials: S
authors.lastname: Vukelja
authors.forename: Vladimir
authors.initials: V
authors.lastname: Moiseyenko
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Ayoub
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Cervantes
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
authors.forename: Stephen
authors.initials: S
authors.lastname: Jones
authors.forename: Wing-Yiu
authors.initials: WY
authors.lastname: Lui
authors.forename: Louis
authors.initials: L
authors.lastname: Mauriac
authors.forename: Chris
authors.initials: C
authors.lastname: Twelves
authors.forename: Guy
authors.initials: G
authors.lastname: Van Hazel
authors.forename: Shailendra
authors.initials: S
authors.lastname: Verma
authors.forename: Robert
authors.initials: R
authors.lastname: Leonard
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D016019:Survival Analysis; D043823:Taxoids; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D017239:Paclitaxel; D005472:Fluorouracil