title: A phase II trial of neoadjuvant gemcitabine, epirubicin, and docetaxel as primary treatment of patients with locally advanced or inflammatory breast cancer.
abstract: BACKGROUND
  Three-drug regimens containing gemcitabine, an anthracycline, and a taxane produce response rates of 70%-90% in patients with metastatic breast cancer (MBC) although accompanied by considerable hematologic toxicity. We explored the combination of gemcitabine/epirubicin/docetaxel as neoadjuvant therapy. Docetaxel was administered weekly to decrease myelosuppression.
  
  
  METHODS
  A total of 110 patients with locally advanced or inflammatory breast cancer received neoadjuvant gemcitabine 800 mg/m2 intravenously (I.V.) days 1 and 8, epirubicin 75 mg/m2 I.V. day 1, and docetaxel 30 mg/m2 I.V. days 1 and 8, repeated every 21 days for 4 cycles. Then patients had either mastectomy or breast conservation surgery, and pathologic treatment responses were assessed. After surgery, 4 cycles of adjuvant gemcitabine 1000 mg/m2 I.V. days 1 and 8 and docetaxel 35 mg/m2 I.V. days 1 and 8 were administered at 21-day intervals. After patients completed chemotherapy, locoregional radiation therapy and/or anti-estrogen therapy was administered per standard guidelines.
  
  
  RESULTS
  Treatment with 4 cycles of neoadjuvant gemcitabine, epirubicin, and weekly docetaxel resulted in an objective response in 79 of 110 patients enrolled (72%; 95% CI, 63-80%). Twenty of 103 patients (19%) who had surgery had pathologic complete response (pCR). Moderate hematologic toxicity was evident during neoadjuvant therapy, with grade 3/4 neutropenia in 41% and febrile neutropenia in 11% of the patients. Protocol-specified dose modifications were required in 35% of the patients, and 58% of the patients used myeloid growth factors.
  
  
  CONCLUSIONS
  The pCR rate of 19% achieved with gemcitabine, epirubicin, and weekly docetaxel confirms previous reports with similar 3-drug regimens. The use of a weekly schedule of docetaxel did not appear to reduce the incidence of grade 3/4 hematologic toxicity.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN, USA.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.forename: Nancy W
authors.initials: NW
authors.lastname: Peacock
authors.forename: Natalie R
authors.initials: NR
authors.lastname: Dickson
authors.forename: Melissa B
authors.initials: MB
authors.lastname: White
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Vázquez
authors.forename: John T
authors.initials: JT
authors.lastname: Foust
authors.forename: Richard
authors.initials: R
authors.lastname: Grapski
authors.forename: Linda K
authors.initials: LK
authors.lastname: Hendricks
authors.forename: William L
authors.initials: WL
authors.lastname: Scott
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D015251:Epirubicin; D000093542:Gemcitabine