Formation of Platinum‐DNA Adducts in Pediatric Patients Receiving Carboplatin

Abstract

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/μg 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.