Therapeutic monitoring of carboplatin dosing in a premature infant with retinoblastoma.
BACKGROUND
Carboplatin dosing based on renal function and therapeutic monitoring have been previously shown to be beneficial in the treatment of children with cancer. However, the applicability of such approaches to the treatment of premature or newborn infants, where kidney function may change markedly with advancing gestational and postnatal age, is unknown. Diagnosis of retinoblastoma in a preterm infant provided a rare opportunity to carry out adaptive carboplatin dosing in a patient with immature renal function.


METHODS
A preterm female infant born at a gestational age of 32 weeks was diagnosed with bilateral retinoblastoma at 35 weeks. Carboplatin treatment with real-time pharmacokinetic monitoring was initiated on day 26 of life at an initial dose of 6.6 mg/kg. Plasma samples were obtained at specified time points and carboplatin levels quantified by atomic absorption spectrometry. Additional doses of carboplatin were determined by pharmacokinetic monitoring based on the achievement of carboplatin AUC values of 5.2-7.8 mg/ml min on three courses of treatment. Increased carboplatin doses administered on successive courses of treatment reflected a greater than twofold increase in drug clearance, from 3.4-7.1 ml/min over a 7-week period. Pharmacokinetically-guided carboplatin dosing led to the attainment of AUCs within 10% of target values on each course of treatment. The patient completed five courses of carboplatin with both tumours defined as inactive after this treatment period.


CONCLUSIONS
Data obtained from studying this patient suggests that adaptive carboplatin monitoring represents a feasible and beneficial clinical approach in preterm infants or neonates.
Picton
S V
SV
Paediatric Oncology Unit, St James's Hospital, Leeds, UK.
Keeble
J
J
Holden
V
V
Errington
J
J
Boddy
A V
AV
Veal
G J
GJ
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007677:Kidney Function Tests; D008657:Metabolic Clearance Rate; D019572:Retinal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012175:Retinoblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014018:Tissue Distribution; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D016190:Carboplatin