When is therapeutic drug monitoring (TDM) of pediatric antineoplastic drugs recommended?
I wrote about TDM in pediatric oncology for
CLN back in 2015 (
1). Since then, the indications for the use of TDM haven’t changed. It is still most useful for drugs that have a narrow therapeutic index, the potential for serious or life-threatening toxicity, or that exhibit substantial intra- and/or inter-patient pharmacokinetic variability. Except for a few cytotoxic drugs such as methotrexate, busulfan, and thiopurines, the use of TDM remains modest for most antineoplastics in the United States.
What has changed in the last 10 years is that guidelines and practical recommendations have been published on the TDM of busulfan, a drug for which monitoring is essential to guide therapy. Additionally, evidence has accumulated supporting the use of TDM for several oral targeted antineoplastic drugs.
Have other new guidelines on this topic come out?
The International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) published consensus guidelines in 2021 that include therapeutic range recommendations for imatinib therapy. Imatinib is a tyrosine kinase inhibitor used for chronic myeloid leukemia. It can also be used to treat Philadelphia chromosome-positive acute lymphoblastic leukemia in children.
In 2018, the IATDMCT also published recommendations supporting the use of TDM of the fluoropyrimidine 5-fluorouracil (5-FU), which is used in pediatrics to treat hepatoblastoma and nasopharyngeal carcinomas. In early 2025, the National Comprehensive Cancer Network updated its clinical guidelines to recommend considering testing dihydropyrimidine dehydrogenase (DPD, the enzyme coded by the
DPYD gene) before initiating treatment with 5-FU. Patients who are DPD-enzyme deficient are at risk of life-threatening toxicity.
Lastly, although not specifically about TDM, the Clinical Pharmacogenetics Implementation Consortium published updated guidelines in 2018 for thiopurine dosing based on
TPMT and
NUDT15 genotypes. Patients who are poor metabolizers for these genes require a 90% dose reduction of mercaptopurines to prevent fatal myelosuppression.
What barriers continue to limit more widespread adoption of TDM for pediatric oncology?
Incomplete understanding of drug pharmacokinetics — especially in pediatrics — is a big barrier. There is a definite need for additional research in this area.
Another barrier is the difficulty of performing TDM. Not all labs have access to advanced analytical techniques such as liquid chromatography-tandem mass spectrometry. However, these techniques have seen more widespread adoption over the last 10 years, and we should continue to see advances that make this technology accessible to more labs.
What other key points should labs keep in mind?
It’s important to realize that TDM is a multidisciplinary exercise and that you don't do this work on your own. You must collaborate with your oncologists, your pharmacists, and your nursing teams. You must coordinate proper specimen logistics, from collection timing to test availability. You also need to be involved in how these results are going to be interpreted, leading to dose adjustment recommendations.
Just as importantly, don't try to do TDM for everything all at once. Pick the most impactful drugs for your patient population and become a TDM champion for those specific drugs.
References
- Molinelli AR. The role of therapeutic drug monitoring in pediatric cancer chemotherapy. CLN 2015; https://myadlm.org/cln/articles/2015/november/the-role-of-therapeutic-drug-monitoring-in-pediatric-cancer-chemotherapy
Alejandro R. Molinelli, PhD, NRCC-CC, is director of the clinical pharmacokinetics laboratory at St. Jude Children’s Research Hospital in Memphis, Tennessee. +Email: [email protected]
Read the full November-December issue of CLN here.
