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Individualized PEGasparaginase dosing guideline
10 protocol, which had a fixed PEGasparaginase dose of 2,500 IU/m2. The asparaginase-related toxicity in both protocols, however, was similar and there was no correla- tion between asparaginase activity levels.28
Based on the popPK model, dosing guidelines were developed taking into account the effect of the treatment phase on PEGasparaginase CL. Next, dose adjustments based on both week and trough levels were suggested tar- geting 100-250 IU/L or the higher range of 250-400 IU/L. These dosing guidelines, however, should first be validat- ed clinically. In addition, the effect of increasing the dose in case of an infection on PEGasparaginase activity levels should be analyzed.
In conclusion, 18% of the inter- and 8% of the intra- patient variability in CL of PEGasparaginase, normalized for BSA, can be explained by i) treatment phase showing a higher CL during induction treatment (protocol 1A) and ii) the occurrence of an infection, which increases the CL. With the popPK model developed in this study,
PEGasparaginase treatment may be individualized further, taking into account these covariates and the dosing guide- lines provided.
Disclosures
RK has non conflicts of interest to declare; RP and IMvdS has received research support and consultancy fees from Jazz Pharmaceuticals and Medac and RM has received travel grants from Shire and Bayer.
Contributions
RK collected the data, performed the analysis, interpreted the data and wrote the manuscript; RM performed the analysis, interpreted the data and wrote the manuscript; RP and IMvdS designed the research, interpreted the data and wrote the manu- script.
Funding
This work was supported by the KiKa foundation.
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