Continuous or repeated prolonged cisplatin infusions in children: a prospective study on ototoxicity, platinum concentrations, and standard serum parameters.
BACKGROUND
To overcome the ototoxicity of cisplatin, single bolus infusions were replaced by repeated prolonged infusions of lower doses or by continuous infusions at still lower infusion rates. However, considering ototoxicity little is, in fact, known about the tolerance of repeated prolonged or continuous infusion in children.


METHODS
Auditory function was monitored along with plasma concentrations of free and total platinum (Pt), and with standard serum parameters (sodium, potassium, calcium, magnesium, phosphate, chloride, and creatinine) in 24 children receiving cisplatin by continuous infusion for the treatment of neuroblastoma and osteosarcoma or by repeated 1 or 6 hr infusions for the treatment of germ cell tumors.


RESULTS
Hearing deteriorated in 10/15 osteosarcoma patients, 2/3 neuroblastoma patients, and 1/6 patients with germ cell tumors. Ototoxicity occurred after cumulative doses between 120 and 360 mg/m(2) cisplatin. In osteosarcoma patients, ototoxicity was associated with a comparatively higher mean plasma concentration of free Pt. However, Pt plasma concentrations did not discriminate between patients with or without ototoxicity. In patients experiencing ototoxicity serum creatinine increased by 45% compared to pre-treatment levels (mean). Serum creatinine increased by 26% in patients without ototoxicity (P < 0.05, Mann-Whitney Rank sum test). Despite standardized hydration, discrete but significant changes of potassium, sodium, magnesium, and phosphate were observed during and/or after cisplatin infusion, which, however, did not discriminate between patients with and without ototoxicity.


CONCLUSIONS
While continuous cisplatin infusions are less nephrotoxic than repeated prolonged infusions, we observed considerable ototoxicity in patients treated with continuous cisplatin infusions, which necessitates further evaluations on the tolerance of continuous cisplatin infusions in children.
Lanvers-Kaminsky
C
C
Department of Paediatric Haematology and Oncology, University Children's Hospital, Albert-Schweitzer Street 33, Muenster, Germany. lanvers@uni-muenster.de
Krefeld
B
B
Dinnesen
A G
AG
Deuster
D
D
Seifert
E
E
Würthwein
G
G
Jaehde
U
U
Pieck
A C
AC
Boos
J
J
D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy; D009447:Neuroblastoma / Q000188:drug therapy; D012516:Osteosarcoma / Q000188:drug therapy; D010984:Platinum / Q000097:blood; D011446:Prospective Studies
D000970:Antineoplastic Agents; D010984:Platinum; D002945:Cisplatin