Regardless of whether an anti-cancer drug is in development or has been used in the clinic for over 50 years, the current approaches used to select a drug dosage for infants often lead to increased risk of morbidity and poor tumour control. This current dosing paradigm, which has grown out of an absence of data, normalizes adult dosages according to age, body weight or body surface area. However, the continued use of such practices in infants is contrary to current knowledge that maturation and development affect drug disposition and exposure-response relationships. This is particularly pertinent to infants with brain tumours. Contemporary treatment for infants with brain tumours has used craniospinal irradiation (CSI) to substitute or delay intensive chemotherapy to avoid the long-term morbidity associated with CSI. For many of the drugs used in these studies, the evaluation of the PK and PD has been inadequate, suffering from low numbers of subjects and heterogeneous populations. Therefore, it is crucial that comprehensive PK and PD studies are conducted of drugs used to treat infants with brain tumours as well as to study the pharmacologic response (e.g., toxicity, efficacy and long-term effects) to these drugs in a large controlled population.
Clinton Stewart, PharmD
Member, Pharmaceutical Department
St. Jude Children’s Research Hospital, Memphis, TN
Dr. Clinton Stewart completed his Doctor of Pharmacy at the University of Tennessee Health Science Center, Memphis. After completing a postdoctoral fellowship at St. Jude under the mentorship of Dr. William E. Evans, Dr. Stewart joined the University of Tennessee College of Pharmacy faculty as an assistant professor and was promoted to associate professor. In 1991, he joined the St. Jude faculty as an assistant member (equivalent of assistant professor) and has moved through the ranks to full member (equivalent of full professor).
He is an active member of the American Society of Clinical Oncology and the American Association of Cancer Research. His research efforts are focused in the area of pediatric clinical pharmacology, addressing clinically relevant problems of cancer therapeutics in infants and children. Current research efforts include the use of preclinical models to enhance design of clinical trials of new agents in children with cancer, and the use of pharmacokinetics (PK) and pharmacodynamics (PD) to optimize drug exposure in children with cancer. Dr. Stewart has authored or co-authored more than 275 peer-reviewed articles and book chapters. He is presently the co-chair of the Pharmacology Committee of the National Institutes of Health-funded Pediatric Brain Tumor Consortium.