Formation of platinum-DNA adducts in pediatric patients receiving carboplatin

Pharmacotherapy. Jul-Aug 1996;16(4):631-7.

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/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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / therapeutic use
  • Carboplatin / blood
  • Carboplatin / metabolism*
  • Carboplatin / therapeutic use
  • Child
  • Child, Preschool
  • Cisplatin / metabolism
  • DNA Adducts / metabolism*
  • Female
  • Humans
  • Infant
  • Leukocytes / chemistry
  • Leukocytes / metabolism*
  • Male
  • Neoplasms / drug therapy
  • Platinum / metabolism*
  • Prospective Studies

Substances

  • Antineoplastic Agents
  • DNA Adducts
  • cisplatin-DNA adduct
  • Platinum
  • Carboplatin
  • Cisplatin