title: Dose-intense capecitabine, oxaliplatin and bevacizumab as first line treatment for metastatic, unresectable colorectal cancer: a multi-centre phase II study.
abstract: BACKGROUND
  Dose intense chemotherapy may improve efficacy with acceptable toxicity. A phase II study was conducted to determine the feasibility of a dose-intense two weekly schedule of capecitabine, oxaliplatin, and bevacizumab in metastatic colorectal cancer (mCRC).
  
  
  METHODS
  49 patients with previously untreated mCRC were recruited. Nineteen received capecitabine (1750 mg/m(2) oral BD days 1-7)oxaliplatin (85 mg/m(2)i.v. day 1) and bevacizumab (5 mg/kg i.v. day 1) using a 14-day cycle (C1750). Following toxicity concerns capecitabine was reduced to 1500 mg/m2oral BD (C1500) and 30 further patients recruited.
  
  
  RESULTS
  Over 80% of patients received at least 75% of planned chemotherapy doses over the first two cycles. At C1750 Grade 3 or higher toxicity occurred in 74% (95% CI 49% to 91%) and on C1500 in 70% (95% CI 51% to 85%). The median progression-free survival was 6.9 months (95% CI 4.7 to 8.7) for C1750 dose and 8.9 months (95% CI 4.1 to 12.4) for C1500. 3 treatment-related deaths occurred.
  
  
  CONCLUSIONS
  Dose intense capecitabine and oxaliplatin with bevacizumab does not show additional efficacy and has potentially significant toxicity. Its use outside of clinical trials is not recommended.
  
  
  BACKGROUND
  ISRCTN41540878.
authors.forename: Christopher G C A
authors.initials: CG
authors.lastname: Jackson
authors.forename: Katrina
authors.initials: K
authors.lastname: Sharples
authors.forename: Paul I
authors.initials: PI
authors.lastname: Thompson
authors.forename: Anne
authors.initials: A
authors.lastname: O'Donnell
authors.forename: Bridget Anne
authors.initials: BA
authors.lastname: Robinson
authors.forename: David J
authors.initials: DJ
authors.lastname: Perez
authors.forename: Jacqui
authors.initials: J
authors.lastname: Adams
authors.forename: Richard
authors.initials: R
authors.lastname: Isaacs
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Deva
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Hinder
authors.affiliation: Cancer Trials New Zealand, University of Auckland, Level 1, Building 505, 85 Park Road, Grafton, Auckland, New Zealand. mp.findlay@auckland.ac.nz.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Findlay
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D000068258:Bevacizumab; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000077150:Oxaliplatin; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil