Abstract
IntroductionAdministration 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. MethodsCarboplatin 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 8year period. Carboplatin was administered over 3days with therapeutic drug monitoring utilised to target cumulative AUC values of 5.2–7.8mg/mlmin. ResultsAUC 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 7.1ml/min and from 7.2 to 16.5ml/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. ConclusionThe 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.
Highlights
Administration of the most appropriate dose of chemotherapy to neonates is challenging and frequently not standardised based on any scientific rationale
Patients were aged between 3 days and 3 weeks old or gestational ages of 52 weeks, 35 weeks and 36 weeks for preterm neonates, and had been diagnosed with retinoblastoma or low risk neuroblastoma, one stage 4s with massive hepatomegaly and respiratory compromise and one localised, unresectable without segmental chromosomal abnormalities presenting with spinal cord compression
Carboplatin doses were modified in real-time based on the daily area under the plasma concentration–time curve (AUC) values observed in seven patients
Summary
The treatment of cancer in very young children represents a major clinical challenge. A key challenge in this area is the limited amount of data available concerning anticancer drug disposition in the neonatal patient population For those drugs where studies have been reported, clearance values have frequently been shown to differ markedly from those seen in older children and adults [6]. In the current study we report on the wider clinical utility of carboplatin therapeutic drug monitoring in nine preterm and full-term neonates being treated for retinoblastoma and low risk neuroblastoma within the first weeks of life Publication of these data in a small but significant patient population allow us to provide clear guidance for clinicians which will positively impact on the future treatment of preterm and full-term neonates with carboplatin. This is clearly an important issue considering a recent report that younger children are at an increased risk of experiencing ototoxicity following treatment with carboplatin [18]
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