Carboplatin pharmacokinetics in young children with brain tumors.

Abstract

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.

• Authors: M E Tonda, R L Heideman, W P Petros, H S Friedman, D J Murry, J H Rodman
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 38 Issue 5 Pg. 395-400 ( 1996) ISSN: 0344-5704 [Print] Germany
• PMID: 8765431 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Etoposide
• Cyclophosphamide
• Carboplatin

Topics

• Adolescent
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, pharmacokinetics, therapeutic use)
• Brain Neoplasms (drug therapy)
• Carboplatin (administration & dosage, pharmacokinetics)
• Child
• Child, Preschool
• Cyclophosphamide (administration & dosage)
• Etoposide (administration & dosage)
• Glomerular Filtration Rate (drug effects)
• Hematologic Diseases (chemically induced)
• Humans
• Prospective Studies
• Reproducibility of Results
• Statistics, Nonparametric