Ewing sarcoma is a bone cancer that can be diagnosed at any age but is most commonly seen in teenagers. Current survival rates are highest in younger children and progressively fall with age, with potentially serious side-effects commonly associated with treatment. Routine tests do not accurately predict who will be cured or will experience increased side effects, which may be related to differences in drug exposures observed in different patient age groups.
The current study will investigate what happens to the key drugs administered to Ewing sarcoma patients following administration, how they are broken down and cleared from the body and what factors are important in determining response and toxicity. This will provide information on how much drug individual patients should be given to ensure they receive the appropriate dose that is effective without leading to excessive toxicity. Through an improved understanding of the clinical pharmacology of these drugs we will look to improve treatment strategies for future patients. This may be particularly important for teenagers and young adults, who may handle drugs differently than younger children. Clinical samples including those for measuring drug levels, investigating genetic differences, and developing toxicity biomarker assays are available for analysis from a clinical trial involving >120 Ewing sarcoma patients. These samples have been collected over a 6-year period and provide a rich source of clinical data for analysis.
Results from the studies carried out will be used to propose changes to dosing regimens for patients of different age groups (infants and younger children, teenagers and adolescents, adults) based on a clear pharmacological rationale. We anticipate the findings will have a significant impact on the future treatment of teenagers and young adults, a currently under-represented population in clinical trials, diagnosed with Ewing sarcoma and other cancers. This will provide an incentive for future clinical pharmacology studies to look at taking forward similar approaches for additional widely used anticancer drugs.
Photograph of the Newcastle Cancer Centre Pharmacology Group (NCCPG) at Newcastle University