Effect of SLCO Polymorphisms on High-Dose Methotrexate Clearance in Pediatric Oncology Patients
Methotrexate is a chemotherapy agent commonly used in pediatric oncology. 'High-dose' methotrexate is used to treat pediatric cancers such as acute lymphoblastic leukemia, non-Hodgkin lymphoma and osteosarcoma. While high-dose methotrexate is effective in treating these cancers (and others), it has many potential side effects which can be serious. Patients who receive high-dose methotrexate require close monitoring in the hospital until the drug is cleared from their system; the speed at which this happens can be different from one person to the next. If a person's body eliminates the drug too slowly, they may have more side effects, but if they eliminate it too quickly, the drug may not work as well to treat their cancer. We want to understand the role that genes (DNA) play in determining how quickly a person's body clears methotrexate and whether or not these differences influences side effects from this medication. Genes form an 'instruction manual' for the body and some genes tell the body how to eliminate methotrexate.
We will perform an initial research study at Vanderbilt followed by a larger study involving four academic children's hospitals. We will use the information from this research for personalized care for each patient based on their genetics to maximize the effectiveness of their chemotherapy while minimizing side effects.