A randomized cross-over trial to determine the effect of Cremophor EL on the pharmacodynamics and pharmacokinetics of carboplatin chemotherapy

S. Loi, D. Rischin, M. Michael, K. Yuen, K. Stokes, A.G. Ellis, Michael Millward, L.K. Webster

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    3 Citations (Scopus)

    Abstract

    Purpose: Paclitaxel, when combined with carboplatin, exhibits a platelet- sparing effect. Paclitaxel is formulated in Cremophor EL (CrEL), which has been shown in preclinical models to reduce haematological toxicity from radiotherapy and chemotherapy. We sought to determine the effect of a 3-h infusion of 20 ml/ m 2 ( equivalent to 175 mg/m(2) paclitaxel) CrEL on myelosuppression following carboplatin chemotherapy, and the effect of CrEL on carboplatin pharmacokinetics. Methods: A total of 16 patients with locally advanced or metastatic cancer were randomized to receive either CrEL or saline over 3 h prior to carboplatin ( area under the curve, AUC, 5 - 7). Each patient was subsequently crossed over to the other treatment. Blood samples were collected at selected time-points for estimation of platinum AUC and 24-h platinum levels. Full blood counts were obtained three times per week. Results: Of the 16 patients randomized, 15 were evaluable. Myelosuppression was measured by percentage fall at nadir and nadir levels. No significant differences were obtained when comparing CrEL and saline with respect to the above end-points after adjusting for multiple testing. There was no evidence to indicate that CrEL altered the pharmacokinetics of carboplatin. Conclusion: CrEL at this dose and schedule does not appear to be a major contributory factor to the platelet-sparing effect of paclitaxel when combined with carboplatin, nor does it alter the pharmacokinetics of carboplatin.
    Original languageEnglish
    Pages (from-to)407-414
    JournalCancer Chemotherapy and Pharmacology
    Volume54
    Issue number5
    DOIs
    Publication statusPublished - 2004

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