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

Volkmar Müller,Volker Möbus,Antje Lehnert,Christian Jackisch,Manfred Glados,Christoph Thomssen,Volker Heilmann,Axel Hinke,Marcus Schmidt,Henryk Borowicz

doi:10.1186/1471-2407-10-430

Abstract

BackgroundThe 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.MethodsPatients with stage II/IIIA EBC (four or more positive lymph nodes) received post-operative intensified dose-dense sequential epirubicin (150 mg/m² every 2 weeks) and paclitaxel (225 mg/m² every 2 weeks) with filgrastim and darbepoetin alfa, 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).ResultsFifty-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.ConclusionsAdministration 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.Trial registrationCurrent Controlled Trials ISRCTN38983527.

Highlights

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
Capecitabine monotherapy is effective after exposure to anthracyclines and taxanes [4], and significantly improves overall survival versus classical cyclophosphamide, methotrexate and 5-fluorouracil (CMF) as first-line therapy [5]
The second discontinued after the first cycle of epirubicin because of febrile neutropenia

Summary

Introduction

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. Regimens containing both an anthracycline and a taxane are standard of care for patients with high-risk early breast cancer (EBC), such as those with four or more positive nodes [1]. Capecitabine monotherapy is effective after exposure to anthracyclines and taxanes [4], and significantly improves overall survival versus classical cyclophosphamide, methotrexate and 5-fluorouracil (CMF) as first-line therapy [5]. The integration of capecitabine into anthracycline and taxane combination regimens appears feasible, the optimal schedule of capecitabine-containing regimens in the adjuvant and neoadjuvant settings needs further investigation

Methods

Results

Conclusion