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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 31patients by bolus i.v. infusion, at doses of 0.70 to 1.50 mg/m 2 . 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 (C max ) of 25.1ng/mL (range, 3.2-99.2 ng/mL) was observed at 15 minutes after administration. The median exposure (AUC 0-6 ), 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, AUC 0-6 and C max 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 AUC 0-6 , 95% confidence interval (1.02-2.09). AUC 0-6 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.

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Cardiac troponin T (CTT) is elevated acutely in animal models of anthracycline cardiotoxicity. We assessed CTT release in children receiving anthracylines using a third generation assay. We measured CTT in 30 children receiving anthracycline chemotherapy. A total of 3 samples were taken from each child: 1) prior to, 2) immediately after and 3) between 24-48 hours after the infusion. The dose range given during the measurements of cardiac troponin T was 15-60 (median 25) mg/m(2) and the previous exposure ranged from 0-300 (median 150) mg/m(2). Not one child had a detectable CTT level at any time. This study shows a lack of acute elevation CTT following anthracycline administration. In this respect it is unlikely that early estimation of CTT using this modern assay will be useful for screening for anthracycline cadiomyopathy. Further studies using a third generation assay, are, however, indicated to determine whether delayed elevation of CTT occurs.