title: Gefitinib in combination with gemcitabine and vinorelbine in patients with metastatic breast cancer pre-treated with taxane and anthracycline chemotherapy: a phase I/II trial.
abstract: OBJECTIVE
  To determine the tolerability and efficacy of the combination of gefitinib with gemcitabine plus vinorelbine in metastatic breast cancer (MBC) patients, pretreated with anthracyclines and taxanes.
  
  
  METHODS
  Women with measurable MBC pretreated with anthracycline- and taxane-based chemotherapy received oral gefitinib (250 mg/day) continuously combined with intravenous gemcitabine 1000 mg/m2 and vinorelbine 25 mg/m2 on day 1, every 2 weeks. The first 10 enrolled patients were evaluated for the safety and tolerability of the proposed fixed-dose regimen.
  
  
  RESULTS
  The study was discontinued prematurely due to low accrual. Twenty-five (71%) of the originally scheduled 35 patients received a total of 154 chemotherapy cycles. All the patients had previously received taxane- and 72% additionally anthracycline-based chemotherapy and 64% of them had progressive disease as best response to first-line treatment. Three episodes of dose-limiting toxicities (one non-febrile neutropenia grade 4 and two non-neutropenic infections grade 3) were observed in the safety analysis of the first 10 patients. In an intent-to-treat analysis, the overall response rate was 12% (95% CI, 0-24.7%), the median time to tumour progression was 3.5 months (range 1.0-11.5) and the median overall survival was 10.4 months (range 1.0-46.0). The main toxicity was hematological, with grade 3 and 4 neutropenia occurring in 6 (24%) and 4 (16%) patients, respectively. Febrile neutropenia occurred in 2 (8.0%) patients.
  
  
  CONCLUSIONS
  Although well tolerated, the gefitinib plus gemcitabine and vinorelbine regimen achieved a low response rate in this prematurely terminated trial and therefore cannot be recommended for women with pretreated MBC.
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Gioulbasanis
authors.forename: Zacharenia
authors.initials: Z
authors.lastname: Saridaki
authors.forename: Antonia
authors.initials: A
authors.lastname: Kalykaki
authors.forename: Lambros
authors.initials: L
authors.lastname: Vamvakas
authors.forename: Kostas
authors.initials: K
authors.lastname: Kalbakis
authors.forename: Michail
authors.initials: M
authors.lastname: Ignatiadis
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Amarantidis
authors.forename: Stylianos
authors.initials: S
authors.lastname: Kakolyris
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavroudis
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D043823:Taxoids / Q000627:therapeutic use; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D018943:Anthracyclines; D001952:Bridged-Ring Compounds; D011799:Quinazolines; D043823:Taxoids; D003841:Deoxycytidine; C080625:taxane; D014747:Vinblastine; D000077235:Vinorelbine; D000077156:Gefitinib; D000093542:Gemcitabine