Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine

OP Friery, R Gallagher, MM Murray, Ciara Hughes, ES Galligan, Irene McIntyre, LH Patterson, DG Hirst, Stephanie McKeown

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Abstract

The ability of the bioreductive drugs AQ4N and tirapazamine to enhance the anti-tumour effect of cyclophosphamide was assessed in three murine tumour models. In male BDF mice implanted with the T50/80 mammary carcinoma, AQ4N (50-150 mg kg(-1)) in combination with cyclophosphamide (100 mg kg(-1)) produced an effect equivalent to a single 200 mg kg(-1) dose of cyclophosphamide. Tirapazamine (25 mg kg(-1)) in combination with cyclophosphamide (100 mg kg(-1)) produced an effect equivalent to a single 150 mg kg(-1) dose of cyclophosphamide. In C3H mice implanted with the SCCVII or RIF-1 tumours, enhancement of tumour cell killing was found with both drugs in combination with cyclophosphamide (50-200 mg kg(-1)); AQ4N (50-200 mg kg(-1)) produced a more effective combination than tirapazamine (12.5-50 mg kg(-1)). Unlike tirapazamine, which showed a significant increase in toxicity to bone marrow cells, the combination of AQ4N (100 mg kg(-1)) 6 h prior to cyclophosphamide (100 mg kg(-1)) resulted in no additional toxicity towards bone marrow cells compared to that caused by cyclophosphamide alone. In conclusion, AQ4N gave a superior anti-tumour effect compared to tirapazamine when administered with a single dose of cyclophosphamide (100 mg kg(-1)). (C) 2000 Cancer Research Campaign.
Original languageEnglish
Pages (from-to)1469-1473
JournalBRITISH JOURNAL OF CANCER
Volume82
Issue number8
Publication statusPublished - Apr 2000

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    Friery, OP., Gallagher, R., Murray, MM., Hughes, C., Galligan, ES., McIntyre, I., Patterson, LH., Hirst, DG., & McKeown, S. (2000). Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine. BRITISH JOURNAL OF CANCER, 82(8), 1469-1473.