title: Cardiac safety of adjuvant pegylated liposomal doxorubicin with concurrent trastuzumab: a randomized phase II trial.
abstract: BACKGROUND
  The cardiac safety of trastuzumab concurrent with pegylated liposomal doxorubicin (PLD) in an adjuvant breast cancer treatment regimen is unknown.
  
  
  METHODS
  Women with resected node-positive or intermediate-risk node-negative HER2 overexpressing breast cancer and baseline left ventricular ejection fraction (LVEF)≥55% were randomized (1:2) to doxorubicin 60 mg/m2 (A)+cyclophosphamide 600 mg/m2 (C) every 21 days (q21d) for four cycles or PLD 35 mg/m2+C q21d+trastuzumab 2 mg/kg weekly (H) for 12 weeks. Both groups then received paclitaxel (Taxol, T) 80 mg/m2 with H for 12 weeks followed by H to complete 1 year. The primary end point was cardiac event rate or inability to administer 1 year of trastuzumab.
  
  
  RESULTS
  Of 181 randomized patients, 179 underwent cardiac analysis. The incidence of cardiac toxicity or inability to administer trastuzumab due to cardiotoxicity was 18.6% [n=11; 95% confidence interval (CI) 9.7% to 30.9%] with A+C→T+H and 4.2% (n=5; 95% CI 1.4% to 9.5%) with PLD+C+H→T+H (P=0.0036). All events, except one, were asymptomatic systolic dysfunction or mildly symptomatic heart failure. Mean absolute LVEF reduction at cycle 8 was greater with doxorubicin (5.6% versus 2.1%; P=0.0014).
  
  
  CONCLUSIONS
  PLD+C+H→T+H is feasible and results in lower early cardiotoxicity rates compared with A+C→T+H.
authors: Department of Medical Oncology, Dalhousie University, Halifax, Canada. daniel.rayson@cdha.nshealth.ca
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authors: Rayson
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mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage; D013318:Stroke Volume / Q000187:drug effects; D000068878:Trastuzumab; D016277:Ventricular Function, Left / Q000187:drug effects; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D000068878:Trastuzumab