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Phase I and pharmacokinetic study of a water-soluble etoposide prodrug, etoposide phosphate (BMY-40481)

Lookup NU author(s): Professor Herbie Newell, Gordon Taylor, Professor Alan Calvert

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Abstract

Etoposide phosphate is a water-soluble prodrug of etoposide. A phase I and pharmacokinetic study has been performed over the dose range 25-110 mg/m(2)/day for 5 days (etoposide equivalent doses). The maximum tolerated dose (MTD) was 110 mg/m(2)/day for 5 days every 3 weeks and the dose-limiting toxicity was neutropenia. Other toxicities were mild, with the exception of 2 patients who displayed significant hypersensitivity reactions. The etoposide phosphate:etoposide area under the plasma concentration versus time curve (AUC) ratio was < 1% and the pharmacokinetic parameters for etoposide were within previously reported ranges. Pharmacodynamic analyses demonstrated that etoposide AUC and baseline white blood cell count were significant determinants of leucopenia (model r(2) = 0.51).


Publication metadata

Author(s): Millward, M. J., Newell, D. R., Mummaneni, V., Igwemezie, L. N., Balmanno, K., Charlton, C. J., Gumbrell, L., Lind, M. J., Chapman, F., Proctor, M., Simmonds, D., Cantwell, B. M. J., Taylor, G. A., McDaniel, C., Winograd, B., Kaul, S., Barbaiya, R. H., Calvert, A. H.

Publication type: Article

Publication status: Published

Journal: European Journal of Cancer

Year: 1995

Volume: 31A

Issue: 13-14

Pages: 2409-2411

Print publication date: 01/12/1995

ISSN (print): 0959-8049

ISSN (electronic): 1879-0852

URL: http://www.ejcancer.info/article/0959-8049(95)00331-2/pdf


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