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Pharmacokinetics of dactinomycin in a pediatric patient population: A United Kingdom Children's Cancer Study Group study

Lookup NU author(s): Professor Gareth Veal, Mike Cole, Julie Errington, Annie Parry, Dr Juliet Hale, Professor Andrew Pearson, Professor Alan Boddy

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Abstract

Purpose: Dactinomycin (actinomycin D) is an antitumor antibiotic used routinely to treat certain pediatric and adult cancers. Despite concerns over the incidence of toxicity, little is known about the pharmacology of dactinomycin. A study was done to investigate dactinomycin pharmacokinetics in children. Experimental Design: Dactinomycin was administered to 31 patients by bolus i.v. infusion, at doses of 0.70 to 1.50 mg/m2. Plasma concentrations were determined by liquid chromatographymass spectrometry up to 24 hours after drug administration and National Cancer Institute Common Toxicity Criteria was assessed. Results: Pharmacokinetic data analysis suggested that a three-compartment model most accurately reflected dactinomycin pharmacokinetics. However, there was insufficient data available to fully characterize this model. A median peak plasma concentration (Cmax) of 25.1 ng/mL (range, 3.2-99.2 ng/mL) was observed at 15 minutes after administration. The median exposure (AUC0-6), determined in 16 patients with sampling to 6 hours, was 2.67 mg/L.min (range, 1.12-4.90 mg/L.min). After adjusting for body size, AUC0-6 and Cmax were positively related to dose (P - 0.03 and P = 0.04, respectively). Patients who experienced any level of Common Toxicity Criteria grade had a 1.46-fold higher AUC0-6, 95% confidence interval (1.02-2.09). AUC0-6 was higher in patients <40 kg, possibly indicating a greater toxicity risk. Conclusions: Data presented suggest that dosing of dactinomycin based on surface area is not optimal, either in younger patients in whom the risk of toxicity is greater, or in older patients where doses are capped. © 2005 American Association for Cancer Research.

Publication metadata

Author(s): Veal, G. J., Cole, M., Errington, J., Parry, A. P., Hale, J. P., Pearson, A. D. J., Howe, K., Chisholm, J., Beane, C., Brennan, B., Waters, F., Glaser, A., Hemsworth, S., McDowell, H., Wright, Y., Pritchard-Jones, K., Pinkerton, R., Jenner, G., Nicholson, J., Elsworth, A., Boddy, A. V.

Publication type: Article

Publication status: Published

Journal: Clinical Cancer Research

Year: 2005

Volume: 11

Issue: 16

Pages: 5893-5899

Print publication date: 15/08/2005

ISSN (print): 1078-0432

ISSN (electronic): 1557-3265

URL: http://dx.doi.org/10.1158/1078-0432.CCR-04-2546

DOI: 10.1158/1078-0432.CCR-04-2546

PubMed id: 16115931

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