AERO-B03: A randomized phase II trial of dose-dense docetaxel in node-positive breast cancer.

647 Background: Administration of taxanes every 2 weeks (q2w), or "dose dense therapy", is one of the most promising chemotherapy regimens in node positive (N+) breast cancer. AERO-B03 is a randomized phase II trial designed to assess the feasibility of docetaxel dose dense regimens in this setting.

METHODS: From December 2003 to September 2004, 100 patients (pts) with N+ breast cancer were randomized to receive 6 TEC (docetaxel 75 mg/m(2), epirubicin 75 mg/m(2) and cyclophosphamide 500 mg/m(2) q3w) (control), 4 EC (epirubicin 100 mg/m(2) and cyclophosphamide 600 mg/m(2) q2w) followed by 4 T (docetaxel 100 mg/m(2) q2w) (dose dense A) or 4 T followed by 4 EC (dose dense B). Pegfilgrastim was administered on day 2 of each cycle. Primary endpoint was grade 4 (G4) toxicity. Any of the 3 arms would be rejected from further study if G4 ≥ 50%. Data were reviewed by an independent safety monitoring committee.

RESULTS: Preliminary results are based on the first 61 pts (21 pts in control, 21 pts in dose dense A, and 19 in dose dense B). Pt characteristics were well balanced between the 3 arms: median age 55 [31-74], pT1 51%, pT2 46%, pT3 3%, pN1 80%, pN2 18%, pN3 2%, conservative surgery in 74%. No toxic deaths were reported. One pt who refused chemotherapy (dose dense A), and another without follow-up (dose dense B) were excluded. Treatment was discontinued for personal reasons in 1 pt in each arm, and for toxicity in 1 pt in dose dense A, and 2 in dose dense B. Mean dose intensities (mg/m(2)/w) were 24, 43 and 43 for docetaxel, 24, 47 and 47 for epirubicin, and 163, 279, and 278 for cyclophosphamide in control, dose dense A and dose dense B respectively. G4 toxicity (% pts) was reported in 33, 35, and 22 (control, dose dense A, dose dense B respectively). G3-4 toxicity rates were 52, 70, and 78, consisting mainly of neutropenia (38, 35, 33), cutaneous toxicity (0, 20, 28), hand foot syndrome (0, 25, 33), neurotoxicity (0, 15, 6), and nausea (0, 15, 6). Febrile neutropenia was infrequent (14%, 5% and 0% of pts).

CONCLUSIONS: Toxicity of docetaxel dose dense arms is consistent with our initial expectations. Based on the study design, both dose dense regimens seem suitable for a future phase III trial. Final results will be presented during the meeting. Trial supported by Sanofi-Aventis and Amgen. [Table: see text].