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The chemopotentiation of cisplatin by the novel bioreductive drug AQ4N.
- Source :
-
British journal of cancer [Br J Cancer] 2001 Aug 17; Vol. 85 (4), pp. 625-9. - Publication Year :
- 2001
-
Abstract
- AQ4N is a bioreductive drug that can significantly enhance the anti-tumour effect of radiation and cyclophosphamide. The aim of this study was to examine the ability of AQ4N to potentiate the anti-tumour effect of cisplatin and to compare it to the chemopotentiation effect of tirapazamine. In the T50/80 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-tumour effect that was approximately 1.5 to 2 times greater than that achieved by a single 4 or 8 mg/kg dose of cisplatin. Tirapazamine (25 mg/kg) administered 2.5 h prior to cisplatin (4 mg/kg) resulted in a small increase in anti-tumour efficacy. AQ4N was also successful in enhancing the anti-tumour effect of cisplatin in the SCCVII and RIF-1 murine tumour models. This resulted in an increased cell kill of greater than 3 logs in both models; this was a greater cell kill than that observed for tirapazamine with cisplatin. Combination of cisplatin with AQ4N or tirapazamine resulted in no additional bone marrow toxicity compared to cisplatin administered alone. In conclusion, AQ4N has the potential to improve the clinical efficacy of cisplatin.<br /> (Copyright 2001 Cancer Research Campaign.)
- Subjects :
- Animals
Anthraquinones pharmacokinetics
Antineoplastic Agents pharmacokinetics
Cisplatin pharmacokinetics
Disease Models, Animal
Drug Interactions
Drug Screening Assays, Antitumor
Female
Mammary Neoplasms, Animal drug therapy
Mice
Prodrugs pharmacokinetics
Tirapazamine
Triazines pharmacokinetics
Triazines pharmacology
Anthraquinones pharmacology
Antineoplastic Agents pharmacology
Cisplatin pharmacology
Prodrugs pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0007-0920
- Volume :
- 85
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- British journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 11506506
- Full Text :
- https://doi.org/10.1054/bjoc.2001.1975