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Formation of platinum-DNA adducts in pediatric patients receiving carboplatin
M E Tonda1, D J Murry, J H Rodman
1Pharmaceutical Sciences Department, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Study Objective:
To determine the extent of platinum-DNA (Pt-DNA) adduct formation in peripheral white blood cells of children with cancer.
Design:
Prospective study.
Setting:
Pediatric research hospital.
Patients:
Twenty-seven children receiving carboplatin as part of therapy as defined by clinical research protocols.
Interventions:
Patients received various dosages of carboplatin over 1, 3, or 24 hours as a primary component of combination chemotherapy for pediatric solid tumors, brain tumors, or large cell lymphoma.
Measurements And Main Results:
The Pt-DNA adducts were detectable in 10 (37%) of 27 patients. The median value was 3.4 fmol Pt/micrograms DNA (range 1.7-31.2 fmol) in patients with measurable values.
Conclusion:
The Pt-DNA adducts were detected less frequently in pediatric patients than reported in adults. Variables that influenced their detection were higher carboplatin dosages or systemic exposure and short (1-3 hrs) versus prolonged (24 hrs) infusions.