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. 2000 Mar 21;82(8):1469–1473. doi: 10.1054/bjoc.1999.1132

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

O P Friery 1, R Gallagher 1, M M Murray 1, C M Hughes 1, E S Galligan 1, I A McIntyre 1, L H Patterson 2, D G Hirst 1, S R McKeown 1
PMCID: PMC2363362  PMID: 10780528

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−1dose 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−1dose 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). © 2000 Cancer Research Campaign

Keywords: AQ4N; tirapazamine; cyclophosphamide, anti-tumour effect

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Selected References

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