The effects of N-acetylcysteine on ifosfamide efficacy in a mouse xenograft model

Background/Aim: Nephrotoxicity is observed in 30% of children treated with ifosfamide. We have shown that n-acetylcysteine (NAC) successfully mitigates nephrotoxicity of ifosfamide in cell and rodent models. However, before this treatment is evaluated clinically, it must be established that NAC does not interfere with the efficacy of ifosfamide. Materials and Methods: Mice implanted with Ewing's sarcoma tumours received the following treatments: saline, ifosfamide, ifosfamide + NAC concurrently, pre-treatment with NAC + ifosfamide, or NAC alone. Results: Median volumes of EW-7 tumour xenografts in mice treated with ifosfamide (n=8), ifosfamide with concurrent NAC therapy (n=7), and NAC pre-treatment (n=6) (p<0.05) were significantly reduced compared to median tumour volumes of control mice (n=6). None of the NAC treatments affected ifosfamide-mediated reduction in tumour volumes. Conclusion: NAC does not interfere with the efficacy of ifosfamide in a EW-7 xenograft model. These results support the clinical evaluation of NAC as a strategy against ifosfamide-induced nephrotoxicity in children.