Does the sequence of gemcitabine and vinorelbine affect their efficacy in non-small cell lung cancer in vitro?

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. MATERIALS AND 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. CONCLUSION 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.