STEADY-STATE LEVELS AND BONE-MARROW TOXICITY OF ETOPOSIDE IN CHILDRENAND INFANTS - DOES ETOPOSIDE REQUIRE AGE-DEPENDENT DOSE CALCULATION

Purpose: Most pediatric treatment protocols specify dose calculations for cytostatic drugs based on body-surface area (BSA). However, for ch ildren less than 1 year of age, calculation guidelines vary. Normally, reduced dosages are recommended with calculations based on body weigh t (BW). However, the optimal dose for infants should take age-dependen t and drug-specific pharmacokinetic parameters into account. Patients and Methods: The current investigation focused on the effects of diffe rent dose-reduction rules on the steady-state levels (Css) of etoposid e and related bone marrow toxicity, One hundred seventy three treatmen t courses in 78 children on a 96-hour continuous infusion schedule wer e monitored for Css (determined by high-performance liquid chromatogra phy [HPLC]), and 100 courses were documented in detail with regard to dose calculation (125 mg/m(2), 4.17/kg, or 2/3 . 4.17/kg) and toxicity . Results: Dose calculation on the basis of BSA led to Css of 4.9 +/- 1.2 mu g/mL, which on the basis of BW was 3.5 +/- 1.1 mu g/mL and 1.95 +/- 0.6 mu g/mL (2/3 . kg-dose), respectively. However, conversion of the latter levels to those expected with the regular square-meter-dos e, resulted in values of 4.7 +/- 1.4 mu g/mL and 4.2 +/- 1.2 mu g/ mL (/125 mg/m(2)). Lower etoposide Css levels resulted in less pronounced thrombocyte and WBC nadirs in the respective groups. The dose-calcula tion rules for infants, therefore, decreased both dose-intensity and r elated toxicity, Etoposide clearance rates related to BW (0.8 +/- 0.3 mL/min/kg) or BW (19 +/- 6 mL/min/m(2)) did not show any differences b etween children and infants, even in the age range of 3 to 12 months. Conclusion: In the case of etoposide, special dose-calculation guideli nes for infants are not substantiated by age-dependent pharmacokinetic s or tolerance. (C) 1995 by American Society of Clinical Oncology.