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  • Title: Docetaxel and paclitaxel inhibit DNA-adduct formation and intracellular accumulation of cisplatin in human leukocytes.
    Author: Ma J, Verweij J, Planting AS, Kolker HJ, Loos WJ, de Boer-Dennert M, van der Burg ME, Stoter G, Schellens JH.
    Journal: Cancer Chemother Pharmacol; 1996; 37(4):382-4. PubMed ID: 8548886.
    Abstract:
    The purpose of this study was to determine the mechanism of the pharmacodynamic interaction between docetaxel/paclitaxel and cisplatin. Cisplatin-induced DNA-adducts and cisplatin accumulation were quantitated in peripheral blood leukocytes (WBC). The WBC were obtained from patients treated with docetaxel or paclitaxel in phase I/II studies and were incubated in vitro with cisplatin. In addition, blank whole-blood samples were obtained from patients and healthy subjects and incubated in intro with cisplatin or docetaxel/paclitaxel and cisplatin. The cisplatin-induced DNA-adduct levels measured in WBC after treatment with docetaxel or paclitaxel were significantly lower than those determined in non-pretreated WBC. Docetaxel and paclitaxel reduced the intracellular accumulation of cisplatin in WBC by 46-47%. If the pharmacodynamic interaction between docetaxel/paclitaxel and cisplatin also occurs in other normal tissues such as bone marrow, it may well contribute to the sequence dependent toxicity that has been observed in clinical studies.
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