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Anticancer research

Antitumor activity of elacytarabine combined with bevacizumab, cetuximab and trastuzumab in human NSCLC xenografts.


PMID 24023287

Abstract

The objective of the present study was to determine the in vivo antitumor activity of elacytarabine, the 5'-elaidic acid ester of arabinofuranosyl cytidine, alone and in combination with bevacizumab, cetuximab and trastuzumab in Vascular endothelial growth factor (VEGF), Epidermal growth factor receptor (EGFR)- and Human epidermal growth factor receptor 2 (HER2)-expressing non-small cell lung cancer xenografts. The antitumor activity of elacytarabine, was tested at the maximal tolerable dose (MTD; 50 mg/kg) and half MTD (25 mg/kg), alone and in combination with the antibodies bevacizumab (5 mg/kg), cetuximab (20 mg/kg) and trastuzumab (4 mg/kg) in two human non-small cell lung cancer xenografts. Elacytarabine exhibited very high activity in the EKVX xenograft at both dose levels, but was inactive in MAKSAX. Neither of the two xenografts were sensitive to bevacizumab or trastuzumab, but the MAKSAX xenograft showed intermediate response to cetuximab. The high sensitivity of EKVX to elacytarabine precluded the assessment of a potential benefit of the combinations with the antibodies. In the elacytarabine-, bevacizumab- and trastuzumab-insensitive MAKSAX xenograft, the combination of either bevacizumab or trastuzumab with elacytarabine at the MTD or half MTD resulted in intermediate activity, suggesting a beneficial effect of the combinations, whereas for cetuximab, the effect was enhanced when combined with elacytarabine given at the MTD, but not half-MTD. The results suggest that elacytarabine could be active in some cases of non-small cell lung cancer, and that the combination of elacytarabine and tyrosine kinase inhibitors may exert important additive or possibly synergistic effects of potential clinical benefit.