title: Cardiac safety profile of prolonged (>or=6 cycles) pegylated liposomal doxorubicin administration in patients with gynecologic malignancies.
abstract: OBJECTIVE
  Pegylated liposomal doxorubicin (PLD) is currently utilized in the management of several solid tumors. While PLD has been shown to be less cardiotoxic than doxorubicin, the safety of prolonged administration (e.g., >or=6 cycles) of the agent remains undefined.
  
  
  METHODS
  A retrospective chart review was performed of the Cleveland Clinic experience from 1997 to 2003 with the prolonged (>or=6 cycles) use of PLD in individuals with gynecologic malignancies. PLD was administered at doses ranging from 20 to 40 mg/m(2) (infused over 1-2 h) with treatment repeated every 4-6 weeks. While on therapy, patients underwent routine evaluation for toxicity, including the performance of multigated acquisition (MUGA) scans for determination of left ventricular ejection fraction (LVEF).
  
  
  RESULTS
  Twenty-two patients (18 ovarian cancer; 3 primary peritoneal cancer, 1 endometrial cancer) met the criteria for inclusion in this analysis. This population had received a median of 4 (range 1-8) chemotherapy regimens before initiation of PLD. No patient had previously received doxorubicin. The median number of PLD cycles and cumulative dose of LD delivered were 8 (range 6-26) and 483 mg/m(2) (256-1699 mg/m(2)), respectively. One or more MUGA scans were obtained in 14 (64%) patients. No patient experienced clinical evidence (physical findings, symptoms) of heart failure. There were no dose reductions due to cardiac dysfunction, and no patient experienced a decline in LVEF to <50%, or a >or=10% reduction compared to a baseline value.
  
  
  CONCLUSIONS
  Prolonged therapy with PLD is possible in appropriately selected patients with advanced gynecologic malignancies. In this clinical setting, cardiac dysfunction does not appear to be a toxicity, which limits the duration of treatment. The development of evidence-based guidelines for monitoring cardiac function in this patient population would be quite useful.
authors.affiliation: Department of Gynecology/Obstetrics and Hematology/Medical Oncology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. uyard@ccf.org
authors.forename: Denise
authors.initials: D
authors.lastname: Uyar
authors.forename: Barbara
authors.initials: B
authors.lastname: Kulp
authors.forename: Gertrude
authors.initials: G
authors.lastname: Peterson
authors.forename: Kristine
authors.initials: K
authors.lastname: Zanotti
authors.forename: Maurie
authors.initials: M
authors.lastname: Markman
authors.forename: Jerome
authors.initials: J
authors.lastname: Belinson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D016889:Endometrial Neoplasms / Q000188:drug therapy*; D005260:Female; D015637:Gated Blood-Pool Imaging; D006331:Heart Diseases / Q000139:chemically induced* / Q000517:prevention & control; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D012189:Retrospective Studies; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin