Carboplatin therapeutic monitoring in preterm and full-term neonates.
INTRODUCTION
Administration of the most appropriate dose of chemotherapy to neonates is particularly challenging and frequently not standardised based on any scientific rationale. We report the clinical utility of carboplatin therapeutic drug monitoring in preterm and full-term neonates within the first month of life.


METHODS
Carboplatin therapeutic monitoring was performed to achieve target drug exposures area under the plasma concentration-time curve (AUC values) in nine preterm and full-term neonates diagnosed with retinoblastoma or neuroblastoma treated over an 8 year period. Carboplatin was administered over 3 days with therapeutic drug monitoring utilised to target cumulative AUC values of 5.2-7.8 mg/ml min.


RESULTS
AUC values achieved were within 15% of target values for the individual courses of treatment in all but one patient (12/13 courses of treatment), with dose modifications of up to 215% required to achieve target AUC values, based on initial mg/kg dosing schedules. Carboplatin clearance determined across three consecutive chemotherapy courses in two patients increased from 3.4 to 7.1 ml/min and from 7.2 to 16.5 ml/min, representing increases of 210-230% over several weeks of treatment. Complete remission was observed in 8/9 patients, with no renal toxicity reported and only one patient experiencing ototoxicity.


CONCLUSION
The study highlights the benefits of utilising therapeutic drug monitoring to achieve target carboplatin AUC values in preterm and full-term neonates treated within the first few weeks of life, particularly in view of marked increases in drug clearance observed over consecutive chemotherapy courses. In the absence of therapeutic drug monitoring, body-weight based dosing is recommended, with dosing guidance provided for both approaches to inform future treatment.
['Veal|Gareth J|GJ|', 'Errington|Julie|J|', 'Hayden|James|J|', 'Hobin|David|D|', 'Murphy|Dermot|D|', 'Dommett|Rachel M|RM|', 'Tweddle|Deborah A|DA|', 'Jenkinson|Helen|H|', 'Picton|Susan|S|']
D000970:Antineoplastic Agents D019540:Area Under Curve D016190:Carboplatin D004334:Drug Administration Schedule D016903:Drug Monitoring D005865:Gestational Age D006801:Humans D007231:Infant, Newborn D007234:Infant, Premature D009447:Neuroblastoma D011237:Predictive Value of Tests D012074:Remission Induction D012175:Retinoblastoma D047929:Term Birth D016896:Treatment Outcome
Carboplatin Neonates Chemotherapy Therapeutic drug monitoring Retinoblastoma Neuroblastoma