Geburtshilfe Frauenheilkd 2008; 68 - FV_Trafo_01_05
DOI: 10.1055/s-0028-1088694

Adjuvant therapy with capecitabine alone or in combination with vinorelbine after dose-dense epirubicin and paclitaxel – A phase I/II study of the AGO study group breast

V Müller 1, A Lehnert 2, M Schmidt 3, M Glados 4, C Jackisch 5, V Möbus 6
  • 1Klinik für Gynäkologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg
  • 2St. Josefs-Hospital Frauenklinik, Wiebaden
  • 3Universitäts-Frauenklinik Mainz, Mainz
  • 4Onkologische Schwerpunktpraxis Hämatologie und internistische Onkologie, Coesfeld, Coesfeld
  • 5Frauenklinik des Klinikums Offenbach, Offenbach
  • 6Klinikum Frankfurt Höchst Frauenklinik, Frankfurt-Höchst

Aims: Dose-dense sequential ETC-regimen (epirubicin 150mg/m2, paclitaxel 225mg/m2 and cyclophosphamide 2500mg/m2 q2wks, each 3x with G-CSF support) as adjuvant therapy in breast cancer patients improves DFS and OAS compared with conventional therapy (Möbus et al. SABCS 2006). The rationale of this study was to substitute cyclophosphamide with the combination of capecitabine and vinorelbine to increase efficacy and reduce toxicity.

Patients and methods: 51 patients with stage II/IIIA breast cancer and ≥4 positive axillary lymph nodes were treated initially with dose-dense, sequential epirubicin and paclitaxel q2wks at doses described above. Further treatment with 4 cycles q3wks of capecitabine alone or in combination with vinorelbine at the following dose levels was planned: Level 1: capecitabine 1000mg/m2 d1–14; level 2: capecitabine 1000mg/m2 d1–14+vinorelbine 25mg/m2 d1+8; level 3: capecitabine 1250mg/m2 d1–14; level 4: capecitabine 1250mg/m2 d1–14+vinorelbine 25mg/m2 d1+8. All patients received darbepoetin to reduce the incidence of anemia.

Results: Dose limiting toxicity (DLT) was reached at level 2 with 5/11 evaluable patients showing DLT, mainly neuropathy. The study was continued at dose level 3 (capecitabine 1250mg/m2 d1–14) where 6/26 patients (23%) developed DTL which was below the predefined rate of 30% considered as acceptable.

Conclusion: The combination of capecitabine and vinorelbine after dose-dense sequential epirubicin and paclitaxel seems not to be feasible due to increased neurotoxicity while capecitabine monotherapy is feasible in this setting. These findings have implications for further strategies to improve dose-dense chemotherapy regimens.

Mammakarzinom - adjuvante Chemotherapie