Dose-dense adjuvant chemotherapy in node-positive breast cancer: docetaxel followed by epirubicin/cyclophosphamide (T/EC), or the reverse sequence (EC/T), every 2 weeks, versus docetaxel, epirubicin and cyclophosphamide (TEC) every 3 weeks. AERO B03 randomized phase II study

Background: Adding a taxane to anthracycline-based adjuvant chemotherapy prolongs survival in node-positive patients but optimal dose and schedule remain undetermined. This study aimed to select a dose-dense regimen for further assessment in phase III studies. Patients and methods: Ninety-nine patients with node-positive invasive breast adenocarcinoma were randomly assigned to docetaxel (Taxotere) (T) 75 mg/m 2 , epirubicin (E) 75 mg/m 2 and cyclophosphamide (C) 500 mg/m 2 (TEC) x 6, every 3 weeks; E 100 mg/m 2 , C 600 mg/m 2 x 4, then T 100 mg/m 2 x 4 (EC→T) or the reverse sequence (T→EC), every 2 weeks, with pegfilgrastim support. The primary end point was the incidence of grade 4 toxicity. Results: Dose intensity was almost doubled with dose-dense regimens, compared with TEC. Twenty-seven patients experienced grade 4 toxicity: 26%, 40% and 18% with TEC, EC →T and To EC, respectively, mainly neutropenia, but febrile neutropenia occurred only in 11%, 10% and 3%. Grade 3-4 nail disorders, hand-foot syndrome and peripheral neuropathy occurred in 46%, 73% and 68% of patients with TEC, EC→T and T→EC, respectively. Conclusions: Dose-dense regimens yield more frequent and severe nonhematological toxic effects than standard dose TEC regimen. Though grade 4 toxicity rates appear acceptable with the T→EC regimen, the incidence of grade 3-4 events makes it difficult to recommend either dose-dense regimen for further investigation.