title: Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule.
abstract: OBJECTIVE
  This phase II study investigated the efficacy, safety, and pharmacokinetics of trastuzumab monotherapy given as first-line treatment once every 3 weeks (3-weekly) in women with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC).
  
  
  METHODS
  Patients with previously untreated HER2-positive MBC received a loading dose of trastuzumab, 8 mg/kg intravenously (IV) and then 6 mg/kg IV at 3-week intervals until disease progression or patient withdrawal.
  
  
  RESULTS
  In total, 105 patients received a median of five cycles of therapy (range, 1 to 35+). The overall response rate was 19% (23% in patients with measurable centrally confirmed immunohistochemistry [IHC] 3+ and/or fluorescence in situ hybridization [FISH] -positive disease) and clinical benefit rate (complete and partial responses plus stable disease for at least 6 months) was 33% (36% in patients with measurable centrally confirmed IHC 3+ and/or FISH-positive disease). Median time to progression was 3.4 months (range, 0.6 to 23.6 months). The most common treatment-related adverse events were rigors, pyrexia, headache, nausea, and fatigue. Median baseline left ventricular ejection fraction was 63%; this did not significantly change over the course of the study. The average exposure to trastuzumab observed in this study was similar to that in previous studies of the weekly regimen. However, as expected, mean trough trastuzumab concentrations were lower and peak levels were higher with 3-weekly trastuzumab compared with weekly treatments.
  
  
  CONCLUSIONS
  Administering higher doses on a 3-weekly schedule did not compromise the efficacy and safety of trastuzumab in women with HER2-positive MBC, and average exposure was similar to that observed with weekly therapy. Three-weekly trastuzumab may represent a convenient alternative to weekly administration.
authors.affiliation: Vall d'Hebron, University Hospital, Department of Medical Oncology, Pg Vall d'Hebron, 119-129, E-08035 Barcelona, Spain. jbaselga@vhebron.net
authors.forename: José
authors.initials: J
authors.lastname: Baselga
authors.forename: Xavier
authors.initials: X
authors.lastname: Carbonell
authors.forename: Noel-Jaime
authors.initials: NJ
authors.lastname: Castañeda-Soto
authors.forename: Michael
authors.initials: M
authors.lastname: Clemens
authors.forename: Michael
authors.initials: M
authors.lastname: Green
authors.forename: Vernon
authors.initials: V
authors.lastname: Harvey
authors.forename: Serafin
authors.initials: S
authors.lastname: Morales
authors.forename: Claire
authors.initials: C
authors.lastname: Barton
authors.forename: Parviz
authors.initials: P
authors.lastname: Ghahramani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007262:Infusions, Intravenous; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab