Dose-DenseFECFollowedbyDose-DenseIxabepiloneasNeoadjuvant TreatmentforBreastCancerPatients:AFeasibilityStudy MATTEOCLAVAREZZA, a ROBERTOBORDONARO, b BRUNODANIELE, c GABRIELLAFERRANDINA, d SANDROBARNI, e MONICATURAZZA, f FRANCESCACOATI, f ANDREADEMATTEIS, g SABINODEPLACIDO, h FRANCESCOCOGNETTI, i NINAANTONINAOLMEO, j FRANCESCOCARROZZA, k PAOLOBRUZZI, l LUCIADELMASTRO l FOR THEGRUPPOITALIANOMAMMELLA

Background. Ixabepilone is an effective chemotherapy in metastatic breast cancer that has been pretreated with anthracyclines and is resistant or refractory to taxanes. Adjuvant dose-dense (DD) chemotherapy is more effective than regimens administered every 3 weeks, especially in hormonal receptor (HR)-negative tumors. Methods. A feasibility study of neoadjuvant DD ixabepilone was conducted in breast cancer patients with tumors measuring at least 2 cm. Patients received 5-fluorouracil 600 mg/m 2 , epirubicin 90 mg/m 2 , and cyclophosphamide 600 mg/m 2 (“FEC” in combination) administered intravenously on day 1 every 14 days with granulocyte-colony stimulating factor (filgrastim) followed by ixabepilone 40 mg/m 2 administered intravenously on day 1 every 14 days with granulocyte-colony stimulating factor. The study’s primary endpoint was feasibility, and the secondary endpoint was pathologic complete response. A two-stage Simon’s design was adopted. Results. Forty-seven patients were enrolled, and 42 were evaluable. For 10 of 42 patients, DD ixabepilone was not feasible. Six (14%) required ixabepilone interruption, and four (9.5%) required ixabepilone dose reduction of 25%. One toxic death occurred. Hematologic grade 3– 4 toxicities included anemia (9.5%), grade 4 neutropenia (2.4%), febrile neutropenia (4.8%), and thrombocytopenia (2.4%). Nonhematologic grade 3– 4 toxicities consisted of fatigue (14.3%), mucositis (14.3%), sensory neuropathy (7.1%), onychopathy (7.1%), and liver toxicity (4.8%). Grade 2 sensory neuropathy lasting longer than 7 days was recorded in 11.9% of patients. Pathologic complete response was observed in 16 of 42 patients (38.1%), including 11 of 23 (47.8%) with HR-negative tumors and 5 of 19 (26.3%) with HR-positive tumors. Conclusion. Despite high activity, DD ixabepilone after DD FEC is poorly tolerated. The Oncologist 2013;18:924 –925 DISCUSSION