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

BMC Cancer. 2010 Aug 16:10:430. doi: 10.1186/1471-2407-10-430.

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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Capecitabine
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Dose-Response Relationship, Drug
  • Epirubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Humans
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Staging
  • Paclitaxel / administration & dosage
  • Pilot Projects
  • Prognosis
  • Risk Factors
  • Survival Rate
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives
  • Vinorelbine
  • Young Adult

Substances

  • Deoxycytidine
  • Epirubicin
  • Vinblastine
  • Capecitabine
  • Paclitaxel
  • Vinorelbine
  • Fluorouracil