title: Trastuzumab associated with successive cytotoxic therapies beyond disease progression in metastatic breast cancer.
abstract: OBJECTIVE
  To determine the activity of successive trastuzumab-containing regimens in HER2-overexpressing metastatic breast cancer (MBC) as well as the response rate (RR), time to progression (TTP), and predictive factors for response.
  
  
  METHODS
  We performed a descriptive retrospective study of trastuzumab activity in patients with HER2-overexpressing MBC treated at our hospital from October 1999 to October 2003.
  
  
  RESULTS
  Fifty-eight patients were evaluated, in whom an overall RR (complete response plus partial response) of 39.7% was obtained for first-time administration of trastuzumab; stable disease (SD) was seen in 29.3%, and the clinical benefit rate was 69%. Median TTP was 6 months (range, 1 months to > 39 months). A total of 31 patients (53.4%) received a second trastuzumab-containing regimen, with an RR of 25.8%; SD was seen in 12.9%, and the clinical benefit rate was 38.7%. Median TTP was 3 months (range, 1 months to > 22 months). A total of 8 patients (14.3%) received a third trastuzumab-containing regimen. The RR for the third trastuzumab regimen was 12.5%; SD was seen in 12.5%, and the clinical benefit rate was 25%. Median TTP was 2 months (range, 1 months to > 12 months). A total of 4 patients (7.1%) received a fourth trastuzumab-containing regimen, with an RR of zero and SD in 25%. Predictive factors for response were disease in soft tissue or bone (P = 0.03; odds ratio [OR], 3.25; 95% confidence interval [CI], 1.08-9.8) and metastases at < 2 sites (P = 0.03; OR, 6.2; 95% CI, 1.25-30.9). We observed a better RR in the second trastuzumab-containing regimen when the patient responded to the first regimen (P = 0.03; OR, 13.2; 95% CI, 1.36-126).
  
  
  CONCLUSIONS
  Trastuzumab-containing regimens beyond disease progression in MBC show activity even in heavily pretreated patients. The activity noted does not allow us to ascertain the independent contribution of trastuzumab in this setting. There were more responses in patients with few metastases in the soft tissues or bone. Patients who have shown a previous response to trastuzumab can show a response to a second trastuzumab-containing regimen.
authors.affiliation: Servicio de Oncologia Medica, Hospital Clinico San Carlos, Madrid, Spain. jagsaenz@yahoo.com
authors.forename: José A
authors.initials: JA
authors.lastname: García-Sáenz
authors.forename: Miguel
authors.initials: M
authors.lastname: Martín
authors.forename: Javier
authors.initials: J
authors.lastname: Puente
authors.forename: Sara
authors.initials: S
authors.lastname: López-Tarruella
authors.forename: Antonio
authors.initials: A
authors.lastname: Casado
authors.forename: Fernando
authors.initials: F
authors.lastname: Moreno
authors.forename: Enrique
authors.initials: E
authors.lastname: Grande
authors.forename: Eduardo
authors.initials: E
authors.lastname: Díaz-Rubio
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D012189:Retrospective Studies; D012983:Soft Tissue Neoplasms / Q000556:secondary; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D014747:Vinblastine; D000068878:Trastuzumab; D000077235:Vinorelbine