title: Sequential administration of dose-dense epirubicin/cyclophosphamide followed by docetaxel/capecitabine for patients with HER2-negative and locally advanced or node-positive breast cancer.
abstract: OBJECTIVE
  Capecitabine is effective against metastatic breast cancer (MBC). We hypothesized that sequential treatment with dose-dense epirubicin/cyclophosphamide (EC) and docetaxel/capecitabine would be active and tolerable in the adjuvant/neoadjuvant setting.
  
  
  METHODS
  In this prospective phase II clinical trial patients with HER2-negative and node-positive or locally advanced tumors were eligible to receive four cycles of EC (100/600 mg/m2) every 2 weeks with G-CSF on days 3-10, followed by four cycles of docetaxel/capecitabine (75/1,000 mg/m2 b.i.d., days 1-14) every 3 weeks.
  
  
  RESULTS
  Fifty-five patients were enrolled with median age of 49, and 80% had hormone receptor-positive disease. The median tumor size was 2.5 cm, with a median of two axillary nodes involved. Seventy-five percent of the first 20 patients had grade 2/3 hand-foot syndrome (HFS). Dose reduction of capecitabine to 800 mg/m2 reduced the grade 2/3 HFS incidence to 31% in the remaining patients. No grade 4/5 toxicities were observed. All 20 patients treated preoperatively responded, with 5 (25%) pathologic complete responses and 3 additional pT0N1 tumors. At a median follow-up of 48 (range 28-60) months, the event-free and overall survival rates are 91 and 98%, respectively.
  
  
  CONCLUSIONS
  Sequential treatment with dose-dense EC followed by docetaxel/capecitabine, using a lower capecitabine dose than that approved for MBC, has an acceptable toxicity profile and encouraging activity when used as neoadjuvant or adjuvant treatment of breast cancer.
authors.affiliation: Department of Medical Oncology, Clínica Universitaria de Navarra, Pamplona, Spain. ynieto@mdanderson.org
authors.forename: Yago
authors.initials: Y
authors.lastname: Nieto
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Aramendía
authors.forename: Jaime
authors.initials: J
authors.lastname: Espinós
authors.forename: Susana
authors.initials: S
authors.lastname: De la Cruz
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernández-Hidalgo
authors.forename: Marta
authors.initials: M
authors.lastname: Santisteban
authors.forename: Leyre
authors.initials: L
authors.lastname: Arbea
authors.forename: Javier
authors.initials: J
authors.lastname: Aristu
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez-Monge
authors.forename: Marta
authors.initials: M
authors.lastname: Moreno
authors.forename: Luis
authors.initials: L
authors.lastname: Pina
authors.forename: Josu
authors.initials: J
authors.lastname: Sola
authors.forename: Gerardo
authors.initials: G
authors.lastname: Zornoza
authors.forename: Fernando Martínez
authors.initials: FM
authors.lastname: Regueira
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000069287:Capecitabine; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005334:Fever / Q000139:chemically induced; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000069287:Capecitabine; D003520:Cyclophosphamide; D003841:Deoxycytidine; D000077143:Docetaxel; D015251:Epirubicin; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids