title: A feasibility study of bevacizumab plus dose-dense doxorubicin-cyclophosphamide (AC) followed by nanoparticle albumin-bound paclitaxel in early-stage breast cancer.
abstract: OBJECTIVE
  Bevacizumab confers benefits in metastatic breast cancer but may be more effective as adjuvant therapy. We evaluated the cardiac safety of bevacizumab plus dose-dense doxorubicin-cyclophosphamide (ddAC) → nanoparticle albumin-bound (nab)-paclitaxel in human epidermal growth factor receptor 2 normal early-stage breast cancer.
  
  
  METHODS
  Eighty patients with normal left ventricular ejection fraction (LVEF) were enrolled. Bevacizumab was administered for 1 year, concurrently with ddAC → nab-paclitaxel then as a single agent. LVEF was evaluated at months 0, 2, 6, 9, and 18. This regimen was considered safe if fewer than three cardiac events or fewer than two deaths from left ventricular dysfunction occurred. Correlative studies of cardiac troponin (cTn) and plasma renin activity (PRA) were conducted.
  
  
  RESULTS
  The median age was 48 years (range, 27-75 years), and baseline LVEF was 68% (53%-82%). After 39 months' median follow-up (5-45 months): median LVEF was 68% (53%-80%) at 2 months (n = 78), 64% (51%-77%) at 6 months (n = 66), 63% (48%-77%) at 9 months (n = 61), and 66% (42%-76%) at 18 months (n = 54). One patient developed symptomatic LV dysfunction at month 15. Common toxicities necessitating treatment discontinuation were hypertension (HTN, 4%), wound-healing complications (4%), and asymptomatic LVEF declines (4%). Neither cTn nor PRA predicted congestive heart failure (CHF) or HTN, respectively.
  
  
  CONCLUSIONS
  Bevacizumab with ddAC → nab-paclitaxel had a low rate of cardiac events; cTn and PRA levels are not predictive of CHF or HTN, respectively. The efficacy of bevacizumab as adjuvant treatment will be established in several ongoing phase III trials.
authors.affiliation: Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, New York 10065, USA. mcarthuh@mskcc.org
authors.forename: Heather L
authors.initials: HL
authors.lastname: McArthur
authors.forename: Hope
authors.initials: H
authors.lastname: Rugo
authors.forename: Benjamin
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authors.lastname: Nulsen
authors.forename: Laura
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authors.lastname: Hawks
authors.forename: Jill
authors.initials: J
authors.lastname: Grothusen
authors.forename: Michelle
authors.initials: M
authors.lastname: Melisko
authors.forename: Mark
authors.initials: M
authors.lastname: Moasser
authors.forename: Matthew
authors.initials: M
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authors.forename: Tiffany
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authors.lastname: Traina
authors.forename: Sujata
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authors.lastname: Patil
authors.forename: Qin
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authors.lastname: Zhou
authors.forename: Richard
authors.initials: R
authors.lastname: Steingart
authors.forename: Chau
authors.initials: C
authors.lastname: Dang
authors.forename: Monica
authors.initials: M
authors.lastname: Morrow
authors.forename: Peter
authors.initials: P
authors.lastname: Cordeiro
authors.forename: Monica
authors.initials: M
authors.lastname: Fornier
authors.forename: John
authors.initials: J
authors.lastname: Park
authors.forename: Andrew
authors.initials: A
authors.lastname: Seidman
authors.forename: Diana
authors.initials: D
authors.lastname: Lake
authors.forename: Theresa
authors.initials: T
authors.lastname: Gilewski
authors.forename: Maria
authors.initials: M
authors.lastname: Theodoulou
authors.forename: Shanu
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authors.lastname: Modi
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Andrea
authors.forename: Nancy
authors.initials: N
authors.lastname: Sklarin
authors.forename: Mark
authors.initials: M
authors.lastname: Robson
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Moynahan
authors.forename: Steven
authors.initials: S
authors.lastname: Sugarman
authors.forename: Jane E
authors.initials: JE
authors.lastname: Sealey
authors.forename: John H
authors.initials: JH
authors.lastname: Laragh
authors.forename: Carmen
authors.initials: C
authors.lastname: Merali
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.forename: Maura N
authors.initials: MN
authors.lastname: Dickler
mesh_terms: D000328:Adult; D000368:Aged; D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000008:administration & dosage / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel