2',2'-difluorodeoxycytidine (dFdC) is an active anticancer drug in different human malignancies. The present study aimed to evaluate if the activity of dFdC in renal tumors could be improved by interferon-alpha (IFN-alpha). The influence of IFN-alpha (4 h) on the cytotoxicity of dFdC was analyzed in vitro by a colorimetric assay. in vivo, nude mice with xenografts from human nephroblastoma (AC-KLxe-12) and renal cell cancer (ACHN, SN12C) were treated by dFdC +/- IFN-alpha. IFN-alpha alone resulted in no growth inhibition in vitro, but pretreatment with IFN-alpha sensitized SN12C and ACHN cells against dFdC. The additional treatment with IFN-alpha increased the CR rate of ACHN- and SN12C-mice (40%; 7%) compared to dFdC alone (20%; 0%). Xenografts from AC-KLxe-12 did all progress. In conclusion, IFN-alpha increased cytotoxicity of dFdC in vitro and tumor responses of renal cell cancer (RCC) in xenografts. Since therapy lacked activity in nephroblastoma, further studies should focus on RCC to compare the efficacy of dFdC and interferons with other types of biochemotherapy.

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