title: Detailed analysis of a randomized phase III trial: can the tolerability of capecitabine plus docetaxel be improved without compromising its survival advantage?
abstract: BACKGROUND
  In a phase III trial, 3-weekly capecitabine (1250 mg/m(2) twice daily days 1-14) plus docetaxel (75 mg/m(2) day 1) demonstrated significantly superior overall survival to 3-weekly docetaxel (100 mg/m(2) day 1). We report a retrospective analysis of the impact of capecitabine/docetaxel dose reduction on safety and efficacy.
  
  
  METHODS
  Safety and efficacy data were analyzed retrospectively according to the actual doses of capecitabine and docetaxel administered.
  
  
  RESULTS
  More patients receiving capecitabine/docetaxel (65%) had dose reductions for adverse events than docetaxel alone (35%). In most patients requiring dose reduction with the combination (80%), capecitabine and docetaxel were simultaneously reduced to 950 mg/m(2) and 55 mg/m(2), respectively. Subsequently, there were fewer cycles (17%) with grade 3/4 adverse events than with the full doses (34%). Time to progression and overall survival appeared to be similar in patients starting the second cycle with reduced doses of capecitabine/docetaxel and those who continued to receive full doses of capecitabine/docetaxel for at least the first four cycles.
  
  
  CONCLUSIONS
  Capecitabine/docetaxel dosing flexibility allows management of side-effects without compromising efficacy. This retrospective analysis, as well as multiple phase II studies of taxanes with reduced-dose capecitabine, shows that reducing the starting dose of capecitabine with docetaxel is a reasonable strategy for the treatment of patients with metastatic breast cancer. In addition, reducing the dose of both agents may be appropriate.
authors.affiliation: Southwest Wales Cancer Institute, Singleton Hospital, Swansea, UK. robert.leonard@swansea-tr.wales.nhs.uk
authors.forename: R
authors.initials: R
authors.lastname: Leonard
authors.forename: J
authors.initials: J
authors.lastname: O'Shaughnessy
authors.forename: S
authors.initials: S
authors.lastname: Vukelja
authors.forename: V
authors.initials: V
authors.lastname: Gorbounova
authors.forename: C A
authors.initials: CA
authors.lastname: Chan-Navarro
authors.forename: D
authors.initials: D
authors.lastname: Maraninchi
authors.forename: N
authors.initials: N
authors.lastname: Barak-Wigler
authors.forename: J J
authors.initials: JJ
authors.lastname: McKendrick
authors.forename: W G
authors.initials: WG
authors.lastname: Harker
authors.forename: A S
authors.initials: AS
authors.lastname: Bexon
authors.forename: C
authors.initials: C
authors.lastname: Twelves
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000069287:Capecitabine; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D005472:Fluorouracil