title: Final results of a phase I/II pilot study of capecitabine with or without vinorelbine after sequential dose-dense epirubicin and paclitaxel in high-risk early breast cancer.
abstract: BACKGROUND
  The integration of the non-cross-resistant chemotherapeutic agents capecitabine and vinorelbine into an intensified dose-dense sequential anthracycline- and taxane-containing regimen in high-risk early breast cancer (EBC) could improve efficacy, but this combination was not examined in this context so far.
  
  
  METHODS
  Patients with stage II/IIIA EBC (four or more positive lymph nodes) received post-operative intensified dose-dense sequential epirubicin (150 mg/m(2) every 2 weeks) and paclitaxel (225 mg/m(2) every 2 weeks) with filgrastim and darbepoetin alpha, followed by capecitabine alone (dose levels 1 and 3) or with vinorelbine (dose levels 2 and 4). Capecitabine was given on days 1-14 every 21 days at 1000 or 1250 mg/m2 twice daily (dose levels 1/2 and 3/4, respectively). Vinorelbine 25 mg/m2 was given on days 1 and 8 of each 21-day course (dose levels 2 and 4).
  
  
  RESULTS
  Fifty-one patients were treated. There was one dose-limiting toxicity (DLT) at dose level 1. At dose level 2 (capecitabine and vinorelbine), five of 10 patients experienced DLTs. Therefore evaluation of vinorelbine was abandoned and dose level 3 (capecitabine monotherapy) was expanded. Hand-foot syndrome and diarrhoea were dose limiting with capecitabine 1250 mg/m2 twice daily. At 35.2 months' median follow-up, the estimated 3-year relapse-free and overall survival rates were 82% and 91%, respectively.
  
  
  CONCLUSIONS
  Administration of capecitabine monotherapy after sequential dose-dense epirubicin and paclitaxel is feasible in node-positive EBC, while the combination of capecitabine and vinorelbine as used here caused more DLTs.
authors: University Medical Center, Hamburg, Department of Gynecology, Martinistrasse 52, 20246 Hamburg, Germany.
authors: Volkmar
authors: V
authors: Müller
authors: Christoph
authors: C
authors: Thomssen
authors: Marcus
authors: M
authors: Schmidt
authors: Manfred
authors: M
authors: Glados
authors: Christian
authors: C
authors: Jackisch
authors: Volker
authors: V
authors: Heilmann
authors: Axel
authors: A
authors: Hinke
authors: Antje
authors: A
authors: Lehnert
authors: Henryk
authors: H
authors: Borowicz
authors: Volker
authors: V
authors: Möbus
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D010865:Pilot Projects; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D055815:Young Adult
chemical_list: D003841:Deoxycytidine; D015251:Epirubicin; D014747:Vinblastine; D000069287:Capecitabine; D017239:Paclitaxel; D000077235:Vinorelbine; D005472:Fluorouracil