Northern Institute for Cancer Research

Therapeutic Drug Monitoring for the Treatment of C

Therapeutic Drug Monitoring for the Treatment of Childhood Cancer Patients

The utility of therapeutic drug monitoring (TDM) relates to the measurement of drug levels in biological samples to individualise patient treatment through adaptation of drug dose. This is conducted with a view to improving drug efficacy and/or reducing toxicity. Over several years our group have identified childhood cancer patient subpopulations who clearly benefit from TDM treatment approaches with specific commonly used chemotherapeutics. These patients include pre-term infants and neonates, anephric patients and patients receiving high dose chemotherapy. Clinical pharmacology studies carried out by our group have not only resulted in benefits to patients actively participating in clinical trials and TDM studies conducted at the clinician’s request, but have also resulted in changes to dosing guidelines implemented across Europe and the introduction of national treatment guidelines stipulating the use of TDM dosing. A particular focus of these studies has been on the commonly used anticancer drug carboplatin, with the treatment of patients frequently adjusted based on individual patient exposure to achieve target drug exposures. This approach to treatment has resulted in several key publications, the development and adoption of national treatment guidelines for carboplatin in neonates and infants and funding from the NIHR to expand this work out as a national programme from 2018.

Publications

Thomas F, Veal GJ, El Balkhi S, Lafont T, Picard N, Brugieres L, Chatelut E, Piguet C. Therapeutic drug monitoring and dose adaptation of cisplatin in a newborn with hepatoblastoma: a case report. Cancer Chemother Pharmacol 2018 82: 361-365

Veal GJ, Errington J, Sastry J, Chisholm J, Brock P, Morgenstern D, Pritchard-Jones K, Chowdhury T. Adaptive dosing of anticancer drugs in neonates – facilitating evidence-based dosing regimens. Cancer Chemother Pharmacol 2016 77: 685-692

Veal GJ, Errington J, Hayden J, Hobin D, Murphy D, Dommett RM, Tweddle DA, Jenkinson H, Picton S. Carboplatin therapeutic monitoring in preterm and full-term neonates. Eur J Cancer 2015 51: 2022-2030

Bardin C, Veal G, Paci A, Chatelut E, Astier A, Leveque D, Widmer N, Beijnen J. Therapeutic drug monitoring in cancer – Are we missing a trick? Eur J Cancer 2014 50: 2005-2009

Veal GJ, Errington J, Rowbotham SE, Illingworth NA, Malik G, Cole M, Daly AK, Pearson ADJ, Boddy AV. Adaptive dosing approaches to the individualization of 13-cis-retinoic acid (isotretinoin) treatment for children with high-risk neuroblastoma. Clin Cancer Res 2013 19: 469-479Carbo TDM

CCLG guidelines