title: Does the sequence of gemcitabine and vinorelbine affect their efficacy in non-small cell lung cancer in vitro?
abstract: BACKGROUND
  We have recently completed a large phase III trial in advanced non-small cell lung cancer (NSCLC) in the elderly which showed that the combination of gemcitabine (GEM) plus vinorelbine (VNR), with GEM administered first, did not improve any outcome as compared with each single drug.
  
  
  METHODS
  The anti-tumor efficacy of different sequences of administration of GEM and VNR was investigated in a small panel of NSCLC cell lines, by using an in vitro cytotoxic assay and isobologram analysis.
  
  
  RESULTS
  Treatment of lung cancer cells with GEM followed by VNR resulted in moderate synergism in one cell line (A549), and in antagonism in two cell lines (H838 and H1355). However, treatment of NSCLC cells with VNR followed by GEM resulted in antagonism in all cell lines.
  
  
  CONCLUSIONS
  The results of this study show that the GEM/VNR combination is not superior to both single agents against NSCLC cells, independently of the schedule of administration of the drugs.
authors.affiliation: Department of Experimental Oncology, National Cancer Institute, Fondazione Pascale, Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: De Luca
authors.forename: Michele
authors.initials: M
authors.lastname: Grassii
authors.forename: Monica R
authors.initials: MR
authors.lastname: Maiello
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Maio
authors.forename: Mario
authors.initials: M
authors.lastname: Mancino
authors.forename: Ermelinda
authors.initials: E
authors.lastname: De Maio
authors.forename: Cesare
authors.initials: C
authors.lastname: Gridelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Perrone
authors.forename: Nicola
authors.initials: N
authors.lastname: Normanno
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy*; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine