Abstract 1618: Carboplatin therapeutic monitoring in preterm and full-term neonates
Authors: Veal Gareth J. , Errington Julie , Hayden James , Hobin David , Murphy Dermot , Dommett Rachel A. , Tweddle Deborah A. , Jenkinson Helen , Picton Susan 
Published: August 2015

Background: Administration of the most appropriate dose of chemotherapy to neonates with cancer is particularly challenging and in many cases is not standardized based on any scientific rationale. We report on the clinical utility of carboplatin therapeutic drug monitoring in preterm and full-term neonates within the first month of life and use the data generated to provide guidance for the treatment of future patients.

Patients and methods: Carboplatin therapeutic monitoring was performed to achieve target drug exposures (AUC values) in nine preterm and full-term neonates diagnosed with retinoblastoma or neuroblastoma over an 8 year period. Carboplatin was administered over 3 days of treatment with therapeutic drug monitoring utilized to target AUC values of 5.2 - 7.8mg/ml.min.

Results: AUC values achieved following therapeutic monitoring were within 15% of the target value 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 the initial mg/kg dosing schedule implemented. Carboplatin clearance values determined across three consecutive courses of chemotherapy in two patients increased from 3.4 to 7.1ml/min and 7.2 to 16.5 ml/min, representing increases of 210% and 230% over periods of 7 and 8 weeks respectively. Complete remission was observed in all seven patients treated for retinoblastoma and in one patient with neuroblastoma, with no renal toxicity reported and only one patient experiencing ototoxicity.

Conclusion: The study highlights the benefits of utilising therapeutic drug monitoring to achieve cumulative target carboplatin AUC values in preterm and full-term neonates treated within the first few weeks of life, particularly in view of the marked increases in drug clearance observed over consecutive courses of chemotherapy. Reducing the likelihood of sensorineural hearing loss may be particularly relevant in the case of neonates with retinoblastoma, where it is likely to have an even greater impact on the quality of life of a child who may also have some degree of visual impairment. In the absence of therapeutic drug monitoring, body-weight based dosing is recommended, with dosing guidance provided for both approaches to inform the treatment of future patients.

Acknowledgements: Work supported by Cancer Research UK, the North of England Children's Cancer Research Fund and the Experimental Cancer Medicine Centre Network.

Citation Format: Gareth J. Veal, Julie Errington, James Hayden, David Hobin, Dermot Murphy, Rachel A. Dommett, Deborah A. Tweddle, Helen Jenkinson, Susan Picton. Carboplatin therapeutic monitoring in preterm and full-term neonates. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1618. doi:10.1158/1538-7445.AM2015-1618