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How a new, online clinical support tool is helping cancer patients

Data science and a free, web-based tool are making it easier to monitor and predict delayed methotrexate clearance.

Methotrexate (MTX) is used to fight a range of cancers in adults and children, including osteosarcoma, acute lymphoblastic leukemia, and several types of lymphoma.

Yet like any number of other life-saving therapies, it can also create complications in certain patients: when administered in high doses, those with some degree of renal failure can’t clear MTX fast enough, which in turn can cause severe toxicity. To complicate matters, MTX itself can cause kidney injury, leading to the delay of its own elimination from the body.

It’s an issue our antidote, Voraxaze (glucarpidase), can help solve. But because it happens so infrequently, it can be difficult for physicians, nurses and pharmacists to know when to administer this rescue medication. Delayed MTX elimination can be an oncologic emergency, but it is defined as occurring only when MTX concentrations are greater than 2 standard deviations of the mean MTX excretion curve specific for the MTX dose; this is not a measure that is readily ascertained from clinical experience. Clinicians also need to account for serum creatine levels (an indicator of kidney function), certain demographic information, and when the sample of MTX concentration was taken.

The bottom line? It’s an understandably difficult calculation to make for healthcare professionals, most of whom have likely not dealt with MTX toxicity before. How can we make MTX pharmacokinetics (PK) easier?

That’s where a new, web-based clinical decision support tool comes in.

Supported by an unrestricted grant from BTG Specialty Pharmaceuticals, a team from the Cincinnati Children’s Hospital Medical Center Department of Pharmacology – led by Dr. Laura Ramsey – created to help monitor and predict delayed MTX clearance.

In a nutshell, here’s how it works: a clinician inputs the age, gender, height, and weight of the patient, the MTX dose and infusion duration, and at least one MTX plasma concentration measurement and one serum creatine measurement. From there, the tool will display the concentration vs. time curve (i.e. the PK curve) for that individual patient, overlaid upon the population-predicted curve for that dose. In doing so, it quickly provides model-informed guidance on the patient’s need for Voraxase, as well as an estimate of when the patient may reach the MTX concentration threshold necessary for hospital discharge.

Aside from its real-time, individualized guidance, the site is just another example of how novel data science is making its way into medicine. The model used to develop, for instance, was based on 31,672 MTX plasma concentrations from 772 patients.

The web-based tool is free and open source. No patient data is stored upon use, however, it does allow clinicians to save data to their local device for future reference. A PDF of the patient’s PK curve can be downloaded, printed or saved.

Complications from high doses of MTX may be relatively rare – yet it’s this very rarity that can make it difficult to diagnose and know how to effectively treat. Fortunately this new, easy-to-use website has the potential to make all the difference. 

A sample concentration vs time curve of an adult lymphoma patient with delayed elimination created by the tool.

A sample concentration vs time curve of an adult lymphoma patient with delayed elimination created by the tool.

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Serious Hypersensitivity Reactions

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