title: Vinorelbine plus 3-weekly trastuzumab in metastatic breast cancer: a single-centre phase 2 trial.
abstract: BACKGROUND
  After two studies reporting response rates higher than 70% in HER2-positive metastatic breast cancer with weekly trastuzumab and vinorelbine, we planned a phase 2 study to test activity of the same combination, with trastuzumab given every 3 weeks.
  
  
  METHODS
  Patients with HER2-positive metastatic breast cancer (3+ at immunohistochemistry or positive at fluorescence in situ hybridization), PS < or =2, normal left-ventricular ejection fraction (LVEF) and no more than one chemotherapy line for metastatic disease were eligible. Vinorelbine (30 mg/m2) was given on days 1 & 8 every 21 and trastuzumab (8 mg/kg day 1, then 6 mg/kg) every 21 days). A single-stage phase 2 design, with p0 = 0.45, p1 = 0.65, type I and II error = 0.10, was applied; 22 objective responses were required in 39 patients.
  
  
  RESULTS
  From Nov 2002 to May 2005, 50 patients were enrolled, with a median age of 54 years (range 31-81). Among 40 patients eligible for response assessment, there were 7 complete and 13 partial responses (overall response rate 50%; 95% exact CI 33.8-66.2); 11 patients had disease stabilization, lasting more than 6 months in 10 cases. Response rate did not vary according to patients and tumor characteristics, type and amount of previous chemotherapy. Within the whole series, median progression-free survival was 9.6 months (95% CI 7.3-12.3), median overall survival 22.7 months (95% CI 19.5-NA). Fifteen patients (30%) developed brain metastases at a median time of 12 months (range 1-25). There was one toxic death due to renal failure in a patient receiving concomitant pamidronate. Twenty-three patients (46%) had grade 3-4 neutropenia, 2 (4%) grade 3 anemia, 4 (8%) febrile neutropenia. Two patients stopped treatment because of grade 2 decline of LVEF and one patient because of grade 2 liver toxicity concomitant with a grade 1 decline of LVEF. One patient stopped trastuzumab after 50 cycles because of grade 1 decline of LVEF.
  
  
  CONCLUSIONS
  Although lower than in initial studies, activity of 3-weekly trastuzumab plus vinorelbine fell within the range of results reported with weekly schedules. Toxicity was prevalently manageable. This combination is safe and active for metastatic breast cancer patients who received adjuvant taxanes with anthracyclines.
authors: Clinical Trials Unit, National Cancer Institute, Via M, Semmola, I-80131 Naples, Italy. linda.demaio@uosc.fondazionepascale.it <linda.demaio@uosc.fondazionepascale.it>
authors: Ermelinda
authors: E
authors: De Maio
authors: Carmen
authors: C
authors: Pacilio
authors: Adriano
authors: A
authors: Gravina
authors: Alessandro
authors: A
authors: Morabito
authors: Francesca
authors: F
authors: Di Rella
authors: Vincenzo
authors: V
authors: Labonia
authors: Gabriella
authors: G
authors: Landi
authors: Francesco
authors: F
authors: Nuzzo
authors: Emanuela
authors: E
authors: Rossi
authors: Pasqualina
authors: P
authors: Silvestro
authors: Gerardo
authors: G
authors: Botti
authors: Maurizio
authors: M
authors: Di Bonito
authors: Maria Pia
authors: MP
authors: Curcio
authors: Franca
authors: F
authors: Formichelli
authors: Franca
authors: F
authors: La Vecchia
authors: Maria
authors: M
authors: Staiano
authors: Nicola
authors: N
authors: Maurea
authors: Giuseppe
authors: G
authors: D'Aiuto
authors: Massimiliano
authors: M
authors: D'Aiuto
authors: Renato
authors: R
authors: Thomas
authors: Giuseppe
authors: G
authors: Signoriello
authors: Francesco
authors: F
authors: Perrone
authors: Andrea
authors: A
authors: de Matteis
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003248:Constipation / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014747:Vinblastine; D000068878:Trastuzumab; D000077235:Vinorelbine