title: Phase II trial of neoadjuvant chemotherapy with docetaxel followed by epirubicin in stage II/III breast cancer.
abstract: OBJECTIVE
  In most neoadjuvant chemotherapy regimens, the taxane is administered either in combination with an anthracycline or after an anthracycline-containing regimen. We sought to test the feasibility, safety, and determine the pathological complete response (pCR) rate of administering docetaxel first followed by epirubicin as neoadjuvant chemotherapy in women with clinical stage II, III breast cancer.
  
  
  METHODS
  Twenty-five women with newly diagnosed clinical stage IIB (n = 10), IIIA (n = 5), or IIIB (n = 10) received 3 cycles of docetaxel 100 mg/M2 intravenously (IV) every 3 weeks followed by 3 cycles of epirubicin 100 mg/M2 IV every 3 weeks. pCR was defined as the absence of invasive cancer in the breast at definitive surgery.
  
  
  RESULTS
  The median primary tumor size was 6 cm (range 1-12 cm), and 13 (52%) women had clinically palpable axillary lymph nodes. Patients received 149 of the 150 planned cycles of docetaxel and epirubicin without treatment delays, and only 3 (12%) patients had a dose reduction of docetaxel. Seven (28%) patients experienced febrile neutropenia, and 9 (36%) patients had grade 3 non-hematological toxicities with diarrhea being the most frequent in 3 (12%) patients. Six (24%) patients had pCR in the breast. Analysis of pre- and post-docetaxel biopsies from a subset of patients documented taxane-induced activation of mitogen-activated and stress-activated protein kinase pathways.
  
  
  CONCLUSIONS
  Neoadjuvant docetaxel followed by epirubicin is well tolerated and active in breast cancer. To our knowledge, this is first description of docetaxel-induced activation of mitogen-activated and stress-activated protein kinase pathways in human breast cancer.
authors.affiliation: Division of Hematology/Oncology and Comprehensive Breast Health Services, Ohio State University Medical Center, Columbus, OH, USA.
authors.forename: Bhuvaneswari
authors.initials: B
authors.lastname: Ramaswamy
authors.forename: Steven P
authors.initials: SP
authors.lastname: Povoski
authors.forename: Chris
authors.initials: C
authors.lastname: Rhoades
authors.forename: Joan
authors.initials: J
authors.lastname: Allen
authors.forename: Marsha
authors.initials: M
authors.lastname: Hauger
authors.forename: Donn
authors.initials: D
authors.lastname: Young
authors.forename: William
authors.initials: W
authors.lastname: Burak
authors.forename: William
authors.initials: W
authors.lastname: Farrar
authors.forename: Lisa
authors.initials: L
authors.lastname: Yee
authors.forename: Kari
authors.initials: K
authors.lastname: Kendra
authors.forename: Sivagurunathan
authors.initials: S
authors.lastname: Somasundaram
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.forename: Charles L
authors.initials: CL
authors.lastname: Shapiro
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D043823:Taxoids / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin