Dr. Carl Panetta


Date: March 22, 2022 @ 4:00PM

Speaker: Dr. Carl Panetta

Affiliation: St. Jude Children’s Research Hospital

Title: Study Design and Therapeutic Drug Monitoring in Pediatric Cancer: A Modeling and Simulation Approach

Abstract: Modeling and simulation is a useful tool for understanding the effects of drug exposure on efficacy and toxicity. It is especially helpful in rare diseases and underrepresented populations such as pediatrics where randomized clinical trials are often challenging to run. Modeling and simulation allow us to effectively leverage the limited data available in these studies to evaluate and compare multiple treatment options in silico in a matter of hours whereas formal randomized clinical trials can only address a few questions and take many years to run. While modeling and simulation is not a replacement for randomized clinical trials, it is a tool that can guide us to more effective trial designs. We have used modeling and simulation approaches to help develop effective treatment strategies for several pediatric cancer therapies including asparaginase and methotrexate in pediatric acute lymphoblastic leukemia and sorafenib in pediatric hepatocellular carcinoma. In the case of asparaginase, modeling and simulation has guided our understanding of how different formulations, doses, and schedules of asparaginase affect the depletion of CSF asparagine—the primary therapeutic endpoint of asparaginase. For methotrexate, modeling and simulation has been used to develop a better understanding of how the folate pathway, the target of methotrexate, is affected by treatment. Finally, for sorafenib, modeling and simulation has helped us design and validate a therapeutic drug monitoring approach that is predicted to reduce the rate of the dose limiting toxicity hand-foot skin reaction while maintaining efficacy. Each of these examples are currently being used in the treatment of pediatric cancer patients to help improve efficacy and reduce toxicity.