title: Multidisciplinary therapy of locally far-advanced or inflammatory breast cancer with fixed perioperative sequence of epirubicin, vinorelbine, and Fluorouracil chemotherapy, surgery, and radiotherapy: long-term results.
abstract: BACKGROUND
  Based on phase II data in advanced breast cancer (BC), the fluorouracil, epirubicin, and vinorelbine (FEN) combination was assessed as perioperative chemotherapy, integrated in a multidisciplinary treatment for locally advanced BC.
  
  
  METHODS
  Patients with newly diagnosed inoperable (stage IIIB or inflammatory) BC. Multimodality treatment protocol consisted of four preoperative courses of fluorouracil (600 mg/m(2) day 1), epirubicin (75 mg/m(2) day 1), and vinorelbine (25 mg/m(2) day1 and day 8), all i.v. every 21 days, followed by radical or conservative surgery according to clinical response and four postoperative identical chemotherapy courses aimed to eradicate micrometastatic disease. Locoregional radiotherapy was offered to all patients after the completion of chemotherapy followed by hormonotherapy according to hormone receptor status. The primary end points of the study were: (a) clinical and pathological response, (b) downstaging and conversion to operable disease, and (c) recurrence-free survival (RFS) and overall survival (OS).
  
  
  RESULTS
  Forty-eight women, one stage IIIA, 27 (56.2%) stage IIIB, two stage IIIC (4.1%), and 12 (25%) with inflammatory BC, aged 34-75 years (median, 52), were accrued. Thirty-eight and 34 patients completed the planned pre- and postoperative chemotherapy, respectively. Totals of 175 and 135 cycles were administered pre- and postoperatively, respectively. Toxicity of both phases, mainly hematologic, was in general acceptable without treatment-related death. Venous reactions were a frequent problem. All but three tumors were converted to operable, 31.3% with breast conservation. The clinical response rate (RR) was 77.7% (22.2% complete) and pathological RR was 73.3% (complete, 20% in both primary and axilla). After a median follow-up of 72 months, 62.5% and 16.7% of patients remain relapse free at 3 and 5 years, respectively, while 83% and 58.3% were alive 3 and 5 years, respectively, after the start of chemotherapy. Median RFS and OS have not yet been reached, and are currently 37+ and 62+ months, respectively.
  
  
  CONCLUSIONS
  This fixed number of FEN perioperative courses schedule followed by radiotherapy is safe and highly active in inducing both local and distant control of locally far-advanced BC. This strategy is at least not inferior to other established regimens or strategies for locally far-advanced BC, while the integration of taxanes or new targeted agents may help show its true value for this challenging clinical entity.
authors.affiliation: First Department of Medical Oncology, St. Savas Anticancer Hospital, 171 Alexandras Avenue, 115 22 Athens, Greece. ardavanis@yahoo.com
authors.forename: Alexandros
authors.initials: A
authors.lastname: Ardavanis
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tryfonopoulos
authors.forename: Georgios
authors.initials: G
authors.lastname: Orphanos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Missitzis
authors.forename: Michael
authors.initials: M
authors.lastname: Karamouzis
authors.forename: Minas
authors.initials: M
authors.lastname: Chrysochoou
authors.forename: Anastasia
authors.initials: A
authors.lastname: Sotiropoulou
authors.forename: Niki
authors.initials: N
authors.lastname: Arnogiannaki
authors.forename: Georgios
authors.initials: G
authors.lastname: Ioannidis
authors.forename: Georgios
authors.initials: G
authors.lastname: Pissakas
authors.forename: Gerassimas
authors.initials: G
authors.lastname: Rigatos
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D015251:Epirubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D015996:Survival Rate; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D015251:Epirubicin; D014747:Vinblastine; D005472:Fluorouracil