Delivery of adjuvant sequential dose-dense FEC–Doc to patients with breast cancer is feasible, but dose reductions and toxicity are dependent on treatment sequence

H. Wildiers (1, 2, 3) , L. Dirix (4) , P. Neven (1) , A. Prové (4) , P. Clement (2) , P. Squifflet (5) , F. Amant (1) , T. Skacel (6, 7) , R. Paridaens (1, 2)

1 Multidisciplinary Breast Center
2 Department of General Medical Oncology [Leuven]
3 Multidisciplinary Breast Centre
4 Department of Medical Oncology
5 IDDI
6 AMGen - Applied Molecular Genetics
7 Department of Medicine

This study prospectively investigates the impact of dose densification and altering sequence of fluorouracil, epirubicin and cyclophosphamide [FEC] and docetaxel [Doc] on dose delivery and tolerability of adjuvant chemotherapy in breast cancer patients. 117 patients with high-risk primary operable breast cancer were randomized (1:1:2:2) to conventional (three cycles of 3-weekly FEC then three cycles of 3-weekly Doc 100 mg/m or reverse sequence) or dose-dense (dd) treatment (four 10- to 11-day cycles of FEC then four 2-weekly cycles of Doc 75 mg/m, or the reverse). In the dd arms, pegfilgrastim was given on day 2 of each cycle, but only as secondary prophylaxis in conventional arms. The primary endpoint was the proportion of patients completing intended cycles at relative dose intensity ≥85% and this was achieved by 95% of patients in each group except for the ddDoc→FEC group (90%). Dose intensity in the dd arms increased by 48% for FEC and 11% for docetaxel, compared with the conventional arms (both  < 0.001). Doc dose reductions were more frequent with dd treatment and when Doc was given after FEC. Grade 3–4 neutropenia was significantly more frequent with conventional treatment, while fatigue and hand–foot syndrome were numerically more common with dd treatment, particularly when Doc was given after FEC. Delivery of adjuvant sequential ddFEC and Doc is feasible with growth factor support, and chemotherapy sequence appeared to affect delivery of target doses and toxicity.

Mots clés: Breast cancer; Chemotherapy; Cyclophosphamide; Docetaxel; Dose densification; Epirubicin; Fluorouracil; Granulocyte colony-stimulating factor; Pegfilgrastim; Relative dose intensity

H. Wildiers, L. Dirix, P. Neven, A. Prové, P. Clement, et al.. Delivery of adjuvant sequential dose-dense FEC–Doc to patients with breast cancer is feasible, but dose reductions and toxicity are dependent on treatment sequence. Breast Cancer Research and Treatment, 2008, 114 (1), pp.103-112. ⟨10.1007/s10549-008-9970-z⟩. ⟨hal-00478329⟩