title: Pegylated liposomal doxorubicin in combination with cyclophosphamide and trastuzumab in HER2-positive metastatic breast cancer patients: efficacy and cardiac safety from the GEICAM/2004-05 study.
abstract: BACKGROUND
  In order to determine the feasibility of substituting pegylated liposomal doxorubicin (PLD) for doxorubicin in combination with cyclophosphamide and trastuzumab as adjuvant therapy, we conducted a phase II study of the combination as first-line therapy in human epidermal growth factor receptor 2 (HER2) overexpressing metastatic breast cancer (MBC).
  
  
  METHODS
  PLD 50 mg/m(2) and cyclophosphamide 600 mg/m(2) were administered every 4 weeks for six cycles; trastuzumab (4 mg/kg loading dose, then 2 mg/kg) was administered weekly for 24 weeks. The primary end point was objective response rate (ORR), and the secondary end points included time to progression (TTP), overall survival (OS), and safety.
  
  
  RESULTS
  Among the 48 evaluable patients, ORR was 68.8% [95% confidence interval (CI) 55.69% to 81.91%], with 6 patients (12.5%) achieving a complete response and 27 (56.2%) a partial response. The median TTP was 12 months (95% CI 9-15.1 months), and the median OS was 34.2 months (95% CI 27.2-41.2 months). Febrile neutropenia was seen in three patients, grade 3 hand-foot syndrome in 29.2% of patients, and grade 3-4 mucositis in 22.9% of patients. Symptomatic congestive heart failure was not observed, and 16.7% of patients experienced grade 2 asymptomatic left ventricular systolic dysfunction.
  
  
  CONCLUSIONS
  The combination of PLD-cyclophosphamide-concurrent trastuzumab is a feasible, safe, and effective first-line regimen for HER2-overexpressing MBC.
authors.affiliation: Medical Oncology Department, Hospital Clínico San Carlos, Madrid. Electronic address: mmartin@geicam.org.
authors.forename: M
authors.initials: M
authors.lastname: Martín
authors.affiliation: Medical Oncology Departmanet, Complejo Hospitalario de Jaén, Jaén.
authors.forename: P
authors.initials: P
authors.lastname: Sánchez-Rovira
authors.affiliation: Medical Oncology Department, Hospital Clinic i Provincial, Barcelona.
authors.forename: M
authors.initials: M
authors.lastname: Muñoz
authors.affiliation: Medical Oncology Department, Hospital Puerta del Mar, Cádiz.
authors.forename: J M
authors.initials: JM
authors.lastname: Baena-Cañada
authors.affiliation: Medical Oncology Department, Hospital Xeral Calde, Lugo.
authors.forename: J R
authors.initials: JR
authors.lastname: Mel
authors.affiliation: Medical Oncology Department, Hospital Germans Trias y Pujol, Badalona.
authors.forename: M
authors.initials: M
authors.lastname: Margeli
authors.affiliation: Medical Oncology Department, Centro Oncologico de Galicia, A Coruña.
authors.forename: M
authors.initials: M
authors.lastname: Ramos
authors.affiliation: Medical Oncology Department, Hospital Provincial de Castellón, Castellón.
authors.forename: E
authors.initials: E
authors.lastname: Martínez
authors.affiliation: Medical Oncology Department, Hospital Clínico San Carlos, Madrid.
authors.forename: J A
authors.initials: JA
authors.lastname: García-Saenz
authors.affiliation: Medical Oncology Department, Hospital Clínico San Carlos, Madrid.
authors.forename: A
authors.initials: A
authors.lastname: Casado
authors.affiliation: Medical Oncology Departmanet, Complejo Hospitalario de Jaén, Jaén.
authors.forename: A M
authors.initials: AM
authors.lastname: Jaén
authors.affiliation: Medical Oncology Department, Hospital Clinic i Provincial, Barcelona.
authors.forename: X
authors.initials: X
authors.lastname: González-Farré
authors.affiliation: GEICAM, Madrid, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Escudero
authors.affiliation: GEICAM, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Rodriguez-Martin
authors.affiliation: GEICAM, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Carrasco
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D004317:Doxorubicin; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C506643:liposomal doxorubicin; C508053:ERBB2 protein, human