title: Neoadjuvant Ixabepilone/Carboplatin/Trastuzumab in HER2-Positive Operable Breast Cancer: A Phase II Trial of the Sarah Cannon Research Institute.
abstract: BACKGROUND
  Ixabepilone is a member of the epothilone class of antineoplastic agents with activity against taxane-resistant tumors, and low susceptibility to common mechanisms of tumor resistance. This study evaluated ixabepilone in lieu of a taxane in combination with carboplatin and trastuzumab as neoadjuvant treatment for operable HER2-positive breast cancer.
  
  
  METHODS
  Patients ≥ 18 years of age with histologically-confirmed HER2-positive adenocarcinoma of the breast (clinical T1-T3, N0-N2, M0), normal left ventricular ejection fraction, and adequate organ function received trastuzumab 6 mg/kg intravenous (I.V.) (with 8 mg/kg loading dose cycle 1), ixabepilone 40 mg/m(2) I.V., and carboplatin area under the curve = 6.0 I.V. on day 1 of each 21-day cycle. Prophylactic growth factor support was permitted. After completing 6 cycles, patients underwent definitive surgery. After surgery, patients continued trastuzumab every 3 weeks for a total of 1 year. Locoregional radiation therapy and endocrine therapy was administered per institutional guidelines. The primary end point was the rate of pCR.
  
  
  RESULTS
  Fifty-eight eligible women (median tumor size, 3.0 cm; clinical axillary lymph node involvement, 67%) initiated treatment between April 2009 and February 2010. Fifty-two patients (90%) underwent surgery, and pCR was observed in 27 patients (52%). Grade 3/4 neutropenia was the most common toxicity, occurring in 69% of patients and complicated by fever in 4 patients.
  
  
  CONCLUSIONS
  The combination of ixabepilone, carboplatin, and trastuzumab was feasible and active as a neoadjuvant regimen. Although the pCR rate of 52% falls within the range reported with other taxane/trastuzumab-based regimens, the greater incidence of severe neutropenia is a disadvantage for this regimen.
authors: Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, PLLC, Nashville, TN. Electronic address: dyardley@tnonc.com.
authors: Denise A
authors: DA
authors: Yardley
authors: Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, PLLC, Nashville, TN.
authors: John D
authors: JD
authors: Zubkus
authors: Florida Cancer Specialists, Fort Myers, FL.
authors: Janice F
authors: JF
authors: Eakle
authors: Oncology Hematology Care, Cincinnati, OH.
authors: Rebecca G
authors: RG
authors: Bechhold
authors: Sarah Cannon Research Institute, Nashville, TN.
authors: Lindsey
authors: L
authors: Finney
authors: Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, PLLC, Chattanooga, TN.
authors: Davey
authors: D
authors: Daniel
authors: Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, PLLC, Chattanooga, TN.
authors: Brooke
authors: B
authors: Daniel
authors: Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, PLLC, Nashville, TN.
authors: John D
authors: JD
authors: Hainsworth
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D034261:Epothilones / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D016190:Carboplatin; D034261:Epothilones; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C430592:ixabepilone
keywords: Biologic; Chemotherapy; Monoclonal antibody