The chemopotentiation of cisplatin by the novel bioreductive drug AQ4N

AQ4N is a bioreductive drug that can significantly enhance the anti-tumour effect of radiation and cyclophosphamide. The aim of this study was to exam ine the ability of AQ4N to potentiate the anti-tumour effect of cisplatin a nd to compare it to the chemopotentiation effect of tirapazamine. In the T5 0/80 murine tumour model, AQ4N (50-100 mg/kg) was administered 30 min, 2.5 or 6 h prior to cisplatin (4 mg/kg or 8 mg/kg); this produced an anti-tumou r effect that was approximately 1.5 to 2 times greater than that achieved b y a single 4 or 8 mg/kg dose of cisplatin. Tirapazamine (25 mg/kg) administ ered 2.5 h prior to cisplatin (4 mg/kg) resulted in a small increase in ant i-tumour efficacy. AQ4N was also successful in enhancing the anti-tumour ef fect of cisplatin in the SCCVII and RIF-1 murine tumour models. This result ed in an increased cell kill of greater than 3 logs in both models; this wa s a greater cell kill than that observed for tirapazamine with cisplatin. C ombination of cisplatin with AQ4N or tirapazamine resulted in no additional bone marrow toxicity compared to cisplatin administered alone. In conclusi on, AQ4N has the potential to improve the clinical efficacy of cisplatin. ( C) 2001 Cancer Research Campaign http://www.bjeancer.com.