Formation of platinum-DNA adducts in pediatric patients receiving carboplatin.
OBJECTIVE
To determine the extent of platinum-DNA (Pt-DNA) adduct formation in peripheral white blood cells of children with cancer.


METHODS
Prospective study.


METHODS
Pediatric research hospital.


METHODS
Twenty-seven children receiving carboplatin as part of therapy as defined by clinical research protocols.


METHODS
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.


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.


CONCLUSIONS
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.
Tonda
M E
ME
Pharmaceutical Sciences Department, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Murry
D J
DJ
Rodman
J H
JH
D000328:Adult; D000970:Antineoplastic Agents / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D016190:Carboplatin / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007962:Leukocytes / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D009369:Neoplasms / Q000188:drug therapy; D010984:Platinum / Q000378:metabolism*; D011446:Prospective Studies
D000970:Antineoplastic Agents; D018736:DNA Adducts; C057270:cisplatin-DNA adduct; D010984:Platinum; D016190:Carboplatin; D002945:Cisplatin