Northern Institute for Cancer Research

Paediatric Pharmacology

Paediatric Pharmacology

About

We conduct a wide range of clinical pharmacology studies across various phases of clinical trials in childhood cancer. We work in close collaboration with academic groups and the CRUK Centre for Drug Development.

Research Leader

Gareth Veal

About

We have over 15 years of experience in conducting clinical pharmacology trials in paediatric oncology settings. 

We run studies in early phase trials. This provides essential pharmacokinetic outputs for the interpretation of clinical data. 

We also run studies designed to optimise the dosing of currently used anticancer drugs in paediatric patient populations.

Staff members at a Research Nurse training day.

Childhood cancer studies

We are the principal national centre for clinical pharmacology studies in childhood cancer in the UK. 

Our trials commonly involve pharmacokinetic, pharmacodynamic and pharmacogenetic aspects.

We perform stand-alone national pharmacology studies. These are sponsored by the Newcastle upon Tyne Hospitals NHS Foundation Trust.

We also run studies as part of larger national and European trials. These are run through the Birmingham CRUK Clinical Trials Unit. 

Several studies have directly impacted on the treatment of children with cancer. They've helped personalise treatment based on therapeutic drug monitoring approaches. 

Results from recent trials have led to changes to dosing regimens. They've also led to the development of new national treatment guidelines for specific drugs based on a pharmacological rationale. 

As part of our role in running national clinical pharmacology trials, we provide training to research nurses across the UK. This ensures that studies are conducted to the same high standards at all clinical centres. This helps to guarantee high quality scientific data.

Facilities

We work within purpose-built clinical pharmacology laboratories within the Paul O’Gorman Building. All our clinical trial work is carried out according to Good Clinical Laboratory Practice regulations.

Our chromatography laboratory has:

  • High Performance Liquid Chromatography
  • Liquid Chromatography-Mass Spectrometry
  • Atomic Absorption Spectrometry

These systems to allow the quantification of a range of anticancer drugs.

We've developed validated assays for over 100 drugs and metabolites. These include both well-established chemotherapeutics and drugs currently in early phase development.

Publications

Veal GJ, Cole M, Chinnaswamy G, Sludden J, Jamieson D, Errington J, Malik G, Hill CR, Chamberlain T, Boddy AV. Cyclophosphamide pharmacokinetics and pharmacogenetics in children with B-cell non-Hodgkin’s lymphoma. Eur J Cancer 2016 55: 56-64.

Jackson RK, Irving JAE, Veal GJ. Personalisation of dexamethasone therapy in childhood acute lymphoblastic leukaemia. Br J Haem 2016 173: 13-24.

Walsh C, Bonner JJ, Johnson TN, Neuhoff S, Ghazaly EA, Gribben JG, Boddy AV, Veal GJ. Development of a physiologically based pharmacokinetic model of actinomycin D in children with cancer. Br J Clin Pharmacol 2016 81: 989-998.

Errington J, Malik G, Evans J, Baston J, Parry A, Price L, Johnstone H, Peters S, Oram V, Howe K, Whiteley E, Tunnacliffe J, Veal GJ. Investigating the experiences of childhood cancer patients and parents participating in optional non-therapeutic clinical research studies in the UK – a qualitative study. Ped Blood Cancer 2016 63: 1193-1197.

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.

Moreno L, Marshall LV, Pearson AD, Morland B, Elliott M, Campbell-Hewson Q, Makin G, Halford SE, Acton G, Ross P, Kazmi-Stokes S, Lock V, Rodriguez A, Lyons  JF, Boddy AV, Griffin MJ, Yule M, Hargrave D. A phase I trial of AT9283 (a selective inhibitor of aurora kinases) in children and adolescents with solid tumors: a Cancer Research UK study. Clin Cancer Res 2015 21: 267-273.

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.

Hill CR, Cole M, Errington J, Malik G, Boddy AV, Veal GJ. Characterisation of the clinical pharmacokinetics of actinomycin D and the influence of ABCB1 pharmacogenetic variation on actinomycin D disposition in children with cancer. Clin Pharmacokinet 2014 53: 741-751.
  
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: 469-479.

Veal GJ, Nguyen L, Paci A, Riggi M, Amiel M, Valteau-Couanet D, Brock P, Ladenstein R, Vassal G. Busulfan pharmacokinetics following intravenous and oral dosing regimens in children receiving high-dose myeloablative chemotherapy for high-risk neuroblastoma as part of the HR-NBL-1/SIOPEN trial. Eur J Cancer 2012 48: 3063-3072.

Jarvis IWH, Meczes EL, Thomas HD, Edmonson RJ, Veal GJ, Boddy AV, Ottley CJ, Pearson DG, Tilby MJ.  Therapy-induced carboplatin-DNA adduct levels in human ovarian tumours in relation to assessment of adduct measurement in mouse tissues. Biochem Pharmacol 2012 83:69-77.

Chinnaswamy G, Errington J, Foot A, Boddy AV, Veal GJ, Cole M. Pharmacokinetics of cyclophosphamide and its metabolites in paediatric patients receiving high-dose myeloablative therapy. Eur J Cancer 2011 47: 1556-1563.

Israels T, Damen CWN, Cole M, van Geloven N, Boddy AV, Caron HN, Beijnen JH, Molyneux EM and Veal GJ. Malnourished Malawian patients presenting with large Wilms tumours have a decreased vincristine clearance rate. Eur J Cancer 2010 46: 1841-1847.

Staff

Gareth Veal

Edward Amankwatia
Philip Berry
Jennifer Bonner
Lulu Cvetkovic
Julie Errington
Melanie Griffin
Claire Hutton
David Jamieson
Julieann Sludden

Postgraduate students:

Rosanna Jackson
Suriyon Uitrakul
Chris Walsh