title: Phase III trial of gemcitabine plus docetaxel versus capecitabine plus docetaxel with planned crossover to the alternate single agent in metastatic breast cancer.
abstract: BACKGROUND
  Safety and efficacy of gemcitabine plus docetaxel (GD) and capecitabine plus docetaxel (CD) were compared in patients with metastatic breast cancer, where the alternate crossover monotherapy (GD→C or CD→G) was predetermined.
  
  
  METHODS
  Patients were randomly assigned to 3-week cycles of either gemcitabine 1000 mg/m(2) on days 1 and 8 plus docetaxel 75 mg/m(2) on day 1 or capecitabine 1000 mg/m(2) twice daily on days 1-14 plus docetaxel 75 mg/m(2) day 1. Upon progression, patients received crossover monotherapy. Primary end point was time to progression (TtP). Secondary end points evaluated overall response rate (ORR), overall survival (OS), and adverse events (AEs).
  
  
  RESULTS
  Despite over-accrual of 475 patients, the trial matured with only 324 of 385 planned TtP events due to patient discontinuations. Human epidermal growth factor receptor 2 status was not captured in this study. More CD patients (28%) discontinued due to AEs than GD patients (18.0%, P = 0.009). TtP [hazard ratio (HR) = 1.101, 95% confidence interval (CI) 0.885-1.370, P = 0.387] and OS (HR = 1.031, 95% CI 0.830-1.280, P = 0.785) were not significantly different comparing GD and CD. ORR was not statistically different (P = 0.239) comparing GD (72 of 207, 34.8%) and CD (78 of 191, 40.8%). TtP, OS, and ORR were not significantly different comparing crossover groups. GD caused greater fatigue, hepatotoxicity, neutropenia, and thrombocytopenia but not febrile neutropenia; CD caused more hand-foot syndrome, gastrointestinal toxicity, and mucositis.
  
  
  CONCLUSIONS
  GD and CD produced similar efficacy and toxicity profiles consistent with prior clinical experience.
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York. Electronic address: seidmana@mskcc.org.
authors.forename: A D
authors.initials: AD
authors.lastname: Seidman
authors.affiliation: Women's Cancer Center, Magee Women's Hospital, Pittsburgh.
authors.forename: A
authors.initials: A
authors.lastname: Brufsky
authors.affiliation: Michiana Hematology Oncology, South Bend.
authors.forename: R H
authors.initials: RH
authors.lastname: Ansari
authors.affiliation: Florida Cancer Specialists, Venice.
authors.forename: L L
authors.initials: LL
authors.lastname: Hart
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt-Ingram Cancer Center, Nashville.
authors.forename: R S
authors.initials: RS
authors.lastname: Stein
authors.affiliation: Hematology and Medical Oncology, The West Clinic, Memphis, USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Schwartzberg
authors.affiliation: Calvary Mater Hospital, Waratah, Australia.
authors.forename: J F
authors.initials: JF
authors.lastname: Stewart
authors.affiliation: Department of Clinical Medicine, University of Southern California, Los Angeles, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Russell
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: S-C
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Centro de Oncologia Rosario, Santa Fe, Argentina.
authors.forename: L E
authors.initials: LE
authors.lastname: Fein
authors.affiliation: Department of Oncology and Clinical Research, Acapulco Oncology Group, Acapulco, Mexico.
authors.forename: J A
authors.initials: JA
authors.lastname: De La Cruz Vargas
authors.affiliation: Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: S-B
authors.initials: SB
authors.lastname: Kim
authors.affiliation: Hospital de Clinicas, Porto Alegre, Brazil.
authors.forename: J
authors.initials: J
authors.lastname: Cavalheiro
authors.affiliation: Lilly USA, LLC, Indianapolis.
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Lilly USA, LLC, Indianapolis.
authors.forename: J F
authors.initials: JF
authors.lastname: Gill
authors.affiliation: Lilly USA, LLC, Indianapolis.
authors.forename: C K
authors.initials: CK
authors.lastname: Obasaju
authors.affiliation: Eli Lilly and Company, Indianapolis, USA.
authors.forename: M
authors.initials: M
authors.lastname: Orlando
authors.affiliation: Lilly USA, LLC, Indianapolis.
authors.forename: D F
authors.initials: DF
authors.lastname: Tai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000069287:Capecitabine; D018592:Cross-Over Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D043823:Taxoids / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine