title: Trastuzumab and gemcitabine as salvage therapy in heavily pre-treated patients with metastatic breast cancer.
abstract: OBJECTIVE
  In Her2-postive metastatic breast carcinoma, first-line trastuzumab-based therapy is well established; many centres continue antibody treatment beyond disease progression. In this trial, we evaluated the efficacy and safety of gemcitabine and trastuzumab after earlier exposure to anthracyclines, docetaxel and/or vinorelbine, and trastuzumab.
  
  
  METHODS
  Twenty-nine consecutive patients were included as eligible. Patients received gemcitabine at a dose of 1,250 mg/m2 on day one and eight, every 21 days. Trastuzumab was administered in three-week cycles. Clinical benefit rate (CBR; CR + PR + SD > or = 6 months) was defined as primary endpoint.
  
  
  RESULTS
  As of July 2007, all patients are evaluable for toxicity, and 26 for response. Earlier therapies consisted of trastuzumab (100%), anthracyclines (100%), vinorelbine (96.6%), docetaxel (72.4%), and capecitabine (72.4%). 19.2% of patients experienced PR, and SD > or = 6 months was observed in a further 26.9%, resulting in a CBR of 46.2%. Time to progression was median 3 months, and overall survival 17 months. Neutropenia (20.7%), thrombocytopenia (13.8%), and nausea (3.4%) were the only treatment-related adverse events that occurred with grade 3 or 4 intensity. Four patients (13.8%) developed brain metastases while on therapy.
  
  
  CONCLUSIONS
  While CBR was low when compared to trastuzumab-based first-line therapy, it is higher than what would be expected from gemcitabine monotherapy in a similar setting. Together with the favourable toxicity profile, this regimen appears to be a safe and potentially effective salvage therapy option in a heavily pre-treated population.
authors.affiliation: First Department of Medicine and Cancer Centre, Clinical Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. rupert.bartsch@meduniwien.ac.at
authors.forename: Rupert
authors.initials: R
authors.lastname: Bartsch
authors.forename: Catharina
authors.initials: C
authors.lastname: Wenzel
authors.forename: Simon P
authors.initials: SP
authors.lastname: Gampenrieder
authors.forename: Ursula
authors.initials: U
authors.lastname: Pluschnig
authors.forename: Gabriela
authors.initials: G
authors.lastname: Altorjai
authors.forename: Margaretha
authors.initials: M
authors.lastname: Rudas
authors.forename: Robert M
authors.initials: RM
authors.lastname: Mader
authors.forename: Peter
authors.initials: P
authors.lastname: Dubsky
authors.forename: Andrea
authors.initials: A
authors.lastname: Rottenfusser
authors.forename: Michael
authors.initials: M
authors.lastname: Gnant
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
authors.forename: Guenther G
authors.initials: GG
authors.lastname: Steger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016879:Salvage Therapy; D000068878:Trastuzumab; D017211:Treatment Failure; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000068878:Trastuzumab; D000093542:Gemcitabine