title: A phase II pilot trial incorporating bevacizumab into dose-dense doxorubicin and cyclophosphamide followed by paclitaxel in patients with lymph node positive breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group.
abstract: BACKGROUND
  E2104 was designed to evaluate the safety of two different strategies incorporating bevacizumab into anthracycline-containing adjuvant therapy as a precursor to a definitive randomized phase III trial.
  
  
  METHODS
  Patients were sequentially assigned to one of two treatment arms. In addition to dose-dense doxorubicin and cyclophosphamide followed by paclitaxel (Taxol) (ddAC→T), all patients received bevacizumab (10 mg/kg every 2 weeks × 26) initiated either concurrently with AC (Arm A: ddBAC→BT→B) or with paclitaxel (Arm B: ddAC→BT→B). The primary end point was incidence of clinically apparent cardiac dysfunction (CHF).
  
  
  RESULTS
  Patients enrolled were 226 in number (Arm A 104, Arm B 122). Grade 3 hypertension, thrombosis, proteinuria and hemorrhage were reported for 12, 2, 2 and <1% of patients, respectively. Two patients developed grade 3 or more cerebrovascular ischemia. Three patients in each arm developed CHF. There was no significant difference between arms in the proportion of patients with an absolute decrease in left ventricular ejection fraction of >15% or >10% to below the lower limit of normal post AC or post bevacizumab.
  
  
  CONCLUSIONS
  Incorporation of bevacizumab into anthracycline-containing adjuvant therapy does not result in prohibitive cardiac toxicity. The definitive phase III trial (E5103) was activated with systematic and extensive cardiac monitoring to define the true impact of bevacizumab on cardiac function.
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, USA. kathmill@iupui.edu
authors.forename: K D
authors.initials: KD
authors.lastname: Miller
authors.forename: A
authors.initials: A
authors.lastname: O'Neill
authors.forename: E A
authors.initials: EA
authors.lastname: Perez
authors.forename: A D
authors.initials: AD
authors.lastname: Seidman
authors.forename: G W
authors.initials: GW
authors.lastname: Sledge
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010865:Pilot Projects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel