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Carboplatin pharmacokinetics in young children with brain tumors.

Publication ,  Journal Article
Tonda, ME; Heideman, RL; Petros, WP; Friedman, HS; Murry, DJ; Rodman, JH
Published in: Cancer Chemother Pharmacol
1996

PURPOSE: The pharmacokinetic parameters and maximal tolerated systemic exposure were determined for carboplatin in young children given in combination with cyclophosphamide and etoposide. PATIENTS AND METHODS: Carboplatin was administered as part of a multiagent chemotherapy regimen to 21 pediatric patients less than 5 years of age with newly diagnosed, malignant central nervous system tumors. Patients, received cyclophosphamide, 1.2 g/m2, on day 1 and carboplatin on day 2 followed by etoposide, 100 mg/m2, each day. Carboplatin doses were calculated to achieve a targeted area under the serum concentration versus time curve (TAUC) of 5, 6.5 or 8 mg/ml.min based on each patient's measured glomerular filtration rate (GFR). Carboplatin pharmacokinetic parameters were determined after course 1 and then after every third course of therapy. RESULTS: The median carboplatin clearance and GFR after course 1 were 118 and 98 ml/min per m2, respectively. Targeted doses based on measured GFR reliably achieved the TAUC for carboplatin. The median (range) carboplatin clearance for four children less than 1 year of age was 76 (66-84) ml/min per m2, significantly lower (P = 0.05) than the value of 131 (80-158) ml/min per m2 for children from 1 to 4 years of age. The mean carboplatin clearance declined by 23% in 12 patients studied from course 1 to course 4 of therapy. The decrease was greater than 20% (range 20-53%) in 7 of the 12 patients studied. CONCLUSION: Carboplatin clearance for children aged between 1 and 4 years at diagnosis is approximately 45% higher than previously reported for pediatric patients, but declines after four courses of therapy. For children less than 1 year of age, carboplatin clearance per square meter is approximately 40% lower than patients 1 to 4 years of age. There are corresponding differences in GFR that provide a plausible explanation for the age and therapy-related changes in carboplatin clearance. Toxicity was acceptable for patients treated at a TAUC of 6.5 mg/ml.min for carboplatin given with etoposide and cyclophosphamide. The average carboplatin dose required for this AUC was 767 mg/m2.

Duke Scholars

Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

1996

Volume

38

Issue

5

Start / End Page

395 / 400

Location

Germany

Related Subject Headings

  • Statistics, Nonparametric
  • Reproducibility of Results
  • Prospective Studies
  • Oncology & Carcinogenesis
  • Humans
  • Hematologic Diseases
  • Glomerular Filtration Rate
  • Etoposide
  • Cyclophosphamide
  • Child, Preschool
 

Citation

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Tonda, M. E., Heideman, R. L., Petros, W. P., Friedman, H. S., Murry, D. J., & Rodman, J. H. (1996). Carboplatin pharmacokinetics in young children with brain tumors. Cancer Chemother Pharmacol, 38(5), 395–400. https://doi.org/10.1007/s002800050502
Tonda, M. E., R. L. Heideman, W. P. Petros, H. S. Friedman, D. J. Murry, and J. H. Rodman. “Carboplatin pharmacokinetics in young children with brain tumors.Cancer Chemother Pharmacol 38, no. 5 (1996): 395–400. https://doi.org/10.1007/s002800050502.
Tonda ME, Heideman RL, Petros WP, Friedman HS, Murry DJ, Rodman JH. Carboplatin pharmacokinetics in young children with brain tumors. Cancer Chemother Pharmacol. 1996;38(5):395–400.
Tonda, M. E., et al. “Carboplatin pharmacokinetics in young children with brain tumors.Cancer Chemother Pharmacol, vol. 38, no. 5, 1996, pp. 395–400. Pubmed, doi:10.1007/s002800050502.
Tonda ME, Heideman RL, Petros WP, Friedman HS, Murry DJ, Rodman JH. Carboplatin pharmacokinetics in young children with brain tumors. Cancer Chemother Pharmacol. 1996;38(5):395–400.
Journal cover image

Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

1996

Volume

38

Issue

5

Start / End Page

395 / 400

Location

Germany

Related Subject Headings

  • Statistics, Nonparametric
  • Reproducibility of Results
  • Prospective Studies
  • Oncology & Carcinogenesis
  • Humans
  • Hematologic Diseases
  • Glomerular Filtration Rate
  • Etoposide
  • Cyclophosphamide
  • Child, Preschool