title: Phase II, open-label trial of lapatinib and vinorelbine in women with previously treated HER2-positive metastatic breast cancer.
abstract: OBJECTIVE
  To evaluate the efficacy and tolerability of lapatinib (L) and intravenous vinorelbine (V) in patients with metastatic HER2-positive breast cancer who have previously received two lines of anti-HER2 therapy (i.e. trastuzumab [T] with chemotherapy and lapatinib with capecitabine [LC]).
  
  
  METHODS
  Consenting patients with measurable or evaluable disease and normal cardiac function who had progressed were recruited. Patients received LV (lapatinib 1250 mg orally daily, vinorelbine 20 mg/m(2) intravenously on days 1 and 8 every 3 weeks) until progressive disease, intolerable toxicity or patient request.
  
  
  RESULTS
  The trial was closed early following inclusion of 19 patients due to slow accrual. Ten, five and four patients had received two, three and more than four lines of chemotherapy with T and LC, respectively, prior to study entry. Patients received a median of 5 cycles (range 1-18) of LV. Confirmed partial response was seen in 2 of 16 patients with measurable disease (12.5%); stable disease >24 weeks was seen in two patients (10.5%) with a clinical benefit rate of 20%. Fatigue and any grade neutropenia occurred commonly, but grade 4 severity occurred in only 5 and 11%, respectively. There were no episodes of cardiac dysfunction and no treatment-related deaths. The median progression-free survival was 3.9 months and overall survival (OS) was 9.1 months.
  
  
  CONCLUSIONS
  The combination of LV demonstrated modest efficacy but was well tolerated. This combination may be of benefit to those patients who are unable to access the newer anti-HER2 agents and the low rate of treatment-emergent adverse effects will enable patients' symptoms, such as pain, to be minimized.
authors.affiliation: Department of Medical Oncology, Breast Cancer Research Centre-WA and Curtin University, Perth, Western Australia, Australia.
authors.forename: Arlene
authors.initials: A
authors.lastname: Chan
authors.forename: Catherine
authors.initials: C
authors.lastname: Shannon
authors.forename: Richard
authors.initials: R
authors.lastname: de Boer
authors.forename: Sally
authors.initials: S
authors.lastname: Baron-Hay
authors.forename: Andrew
authors.initials: A
authors.lastname: Redfern
authors.forename: Astrid
authors.initials: A
authors.lastname: Bauwens
authors.forename: Paul
authors.initials: P
authors.lastname: Craft
authors.forename: Suzanne
authors.initials: S
authors.lastname: Webb
authors.forename: Amanda
authors.initials: A
authors.lastname: Townsend
authors.forename: Dusan
authors.initials: D
authors.lastname: Kotasek
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D011799:Quinazolines; D011859:Radiography; D066066:Response Evaluation Criteria in Solid Tumors; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D011799:Quinazolines; D000077341:Lapatinib; D014747:Vinblastine; D000077235:Vinorelbine
keywords: HER2-positive breast cancer; lapatinib/capecitabine; post-trastuzumab