title: Feasibility and cardiac safety of pegylated liposomal doxorubicin plus trastuzumab in heavily pretreated patients with recurrent HER2-overexpressing metastatic breast cancer.
abstract: BACKGROUND
  Few studies have evaluated concomitant pegylated liposomal doxorubicin (PLD) plus trastuzumab as therapy for HER2-overexpressing metastatic breast cancer (MBC). This open-label, prospective, phase II trial assessed the safety and efficacy of this regimen, with cardiac tolerance as the principal focus.
  
  
  METHODS
  Women with HER2-overexpressing recurrent MBC, baseline left ventricular ejection fraction >or= 55%, and no history of serious cardiac illness were eligible; preexisting cardiac risk factors, including previous anthracyclines and previous trastuzumab for MBC, were allowed. Patients received weekly trastuzumab and every-3-week PLD until progression, prohibitive toxicity, or patient refusal. Left ventricular ejection fraction was assessed during and after therapy. Grade 3/4 congestive heart failure (CHF) was monitored for premature closure.
  
  
  RESULTS
  The trial closed after 2.5 years for slow accrual. Twelve patients were enrolled: 7 had received adjuvant anthracyclines; 9 had received previous MBC treatment, of whom 7 had received trastuzumab in combination with chemotherapy. Patients received a mean of 4.8 cycles of PLD; 8 patients experienced stable disease; 4 patients experienced progression. Mean left ventricular ejection fraction levels did not change substantially: 60.4%, 57%, 60.3%, and 56.8% at baseline, after cycle 2, after cycle 4, and after completion of treatment, respectively. No patients experienced grade 4 CHF. One patient discontinued treatment after grade 3 CHF. Three patients experienced grade 2 left ventricular dysfunction, of whom 2 discontinued treatment. Cardiac function improved in all 4 patients after going off study. Other adverse events were generally mild (grade 1/2) and infrequent.
  
  
  CONCLUSIONS
  Pegylated liposomal doxorubicin plus trastuzumab might be an option for heavily pretreated patients with recurrent HER2-overexpressing MBC.
authors.affiliation: Department of Medical Oncology, New York University Medical Center, New York, NY 10016, USA. andree02@med.nyu.edu
authors.forename: Eleni
authors.initials: E
authors.lastname: Andreopoulou
authors.forename: Darci
authors.initials: D
authors.lastname: Gaiotti
authors.forename: Eugene
authors.initials: E
authors.lastname: Kim
authors.forename: Matthew
authors.initials: M
authors.lastname: Volm
authors.forename: Ruth
authors.initials: R
authors.lastname: Oratz
authors.forename: Robin
authors.initials: R
authors.lastname: Freedberg
authors.forename: Andrea
authors.initials: A
authors.lastname: Downey
authors.forename: Charles L
authors.initials: CL
authors.lastname: Vogel
authors.forename: Stephen
authors.initials: S
authors.lastname: Chia
authors.forename: Franco
authors.initials: F
authors.lastname: Muggia
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D005240:Feasibility Studies; D005260:Female; D018734:Genes, erbB-2; D006331:Heart Diseases / Q000139:chemically induced* / Q000517:prevention & control; D006333:Heart Failure / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D000068878:Trastuzumab; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004317:Doxorubicin; D000068878:Trastuzumab