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Medline ® Abstract for Reference 210

of 'Infusion reactions to systemic chemotherapy'

Phase I and pharmacokinetic study of a water-soluble etoposide prodrug, etoposide phosphate (BMY-40481).
Millward MJ, Newell DR, Mummaneni V, Igwemezie LN, Balmanno K, Charlton CJ, Gumbrell L, Lind MJ, Chapman F, Proctor M
Eur J Cancer. 1995;31A(13-14):2409.
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/m2/day for 5 days (etoposide equivalent doses). The maximum tolerated dose (MTD) was 110 mg/m2/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 r2 = 0.51).
University Department of Clinical Oncology, Newcastle General Hospital, Newcastle Upon Tyne, U.K.