Dose-dense FEC followed by dose-dense ixabepilone as neoadjuvant treatment for breast cancer patients: a feasibility study.
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.


CONCLUSIONS
Despite high activity, DD ixabepilone after DD FEC is poorly tolerated.
E.O. Ospedali Galliera, Genoa, Italy. matteo.clavarezza@galliera.it
Matteo
M
Clavarezza
Roberto
R
Bordonaro
Bruno
B
Daniele
Gabriella
G
Ferrandina
Sandro
S
Barni
Monica
M
Turazza
Francesca
F
Coati
Andrea
A
De Matteis
Sabino
S
De Placido
Francesco
F
Cognetti
Nina Antonina
NA
Olmeo
Francesco
F
Carrozza
Paolo
P
Bruzzi
Lucia
L
Del Mastro
D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000453:epidemiology / Q000473:pathology*; D015251:Epirubicin / Q000008:administration & dosage; D034261:Epothilones / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans
D034261:Epothilones; D015251:Epirubicin; D003520:Cyclophosphamide; C430592:ixabepilone; D005472:Fluorouracil