Dose-dense FEC followed by dose-dense ixabepilone as neoadjuvant treatment for breast cancer patients: a feasibility study
Matteo Clavarezza, Roberto Bordonaro, Bruno Daniele, Gabriella Ferrandina, Sandro Barni, Monica Turazza, Francesca Coati, Andrea De Matteis, Sabino De Placido, Francesco Cognetti, Nina Antonina Olmeo, Francesco Carrozza, Paolo Bruzzi, Lucia Del Mastro, Gruppo Italiano Mammella, Matteo Clavarezza, Roberto Bordonaro, Bruno Daniele, Gabriella Ferrandina, Sandro Barni, Monica Turazza, Francesca Coati, Andrea De Matteis, Sabino De Placido, Francesco Cognetti, Nina Antonina Olmeo, Francesco Carrozza, Paolo Bruzzi, Lucia Del Mastro, Gruppo Italiano Mammella
Abstract
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.
Trial registration: ClinicalTrials.gov NCT00751868.
Source: PubMed