Renal function-based versus standard dosing of pemetrexed: a randomized controlled trial

Nikki de Rouw; René J Boosman; Jacobus A Burgers; Alwin D R Huitema; Anne-Marie C Dingemans; Hieronymus J Derijks; David M Burger; Berber Piet; Lizza E L Hendriks; Bonne Biesma; Melinda A Pruis; Daphne W Dumoulin; Sander Croes; Ron H J Mathijssen; Michel M van den Heuvel; Rob Ter Heine

doi:10.1007/s00280-022-04489-1

Renal function-based versus standard dosing of pemetrexed: a randomized controlled trial

Nikki de Rouw, René J Boosman^*, Jacobus A Burgers, Alwin D R Huitema, Anne-Marie C Dingemans, Hieronymus J Derijks, David M Burger, Berber Piet, Lizza E L Hendriks, Bonne Biesma, Melinda A Pruis, Daphne W Dumoulin, Sander Croes, Ron H J Mathijssen, Michel M van den Heuvel, Rob Ter Heine

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

PURPOSE: Pemetrexed is a chemotherapeutic drug in the treatment of non-small cell lung cancer and mesothelioma. Optimized dosing of pemetrexed based on renal function instead of body surface area (BSA) is hypothesized to reduce pharmacokinetic variability in systemic exposure and could therefore improve treatment outcomes. The aim of this study is to compare optimized dosing to standard BSA-based dosing.

METHODS: A multicenter randomized (1:1) controlled trial was performed to assess superiority of optimized dosing versus BSA-based dosing in patients who were eligible for pemetrexed-based chemotherapy. The individual exposure to pemetrexed in terms of area under the concentration-time curve (AUC) was determined. The fraction of patients attaining to a predefined typical target AUC (164 mg × h/L ± 25%) was calculated.

RESULTS: A total of 81 patients were included. Target attainment was not statistically significant different between both arms (89% vs. 84% (p = 0.505)). The AUC of pemetrexed was similar between the optimized dosing arm (n = 37) and the standard of care arm (n = 44) (155 mg × h/L vs 160 mg × h/L (p = 0.436).

CONCLUSION: We could not show superiority of optimized dosing of pemetrexed in patients with an adequate renal function does not show added value on the attainment of a pharmacokinetic endpoint, safety, nor QoL compared to standard of care dosing.

CLINICAL TRIAL NUMBER: Clinicaltrials.gov identifier: NCT03655821.

Original language	English
Pages (from-to)	33-42
Number of pages	10
Journal	Cancer Chemotherapy and Pharmacology
Volume	91
Issue number	1
Early online date	21 Nov 2022
DOIs	https://doi.org/10.1007/s00280-022-04489-1
Publication status	Published - Jan 2023

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de Rouw, N., Boosman, R. J., Burgers, J. A., Huitema, A. D. R., Dingemans, A.-M. C., Derijks, H. J., Burger, D. M., Piet, B., Hendriks, L. E. L., Biesma, B., Pruis, M. A., Dumoulin, D. W., Croes, S., Mathijssen, R. H. J., van den Heuvel, M. M., & Ter Heine, R. (2023). Renal function-based versus standard dosing of pemetrexed: a randomized controlled trial. Cancer Chemotherapy and Pharmacology, 91(1), 33-42. https://doi.org/10.1007/s00280-022-04489-1

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title = "Renal function-based versus standard dosing of pemetrexed: a randomized controlled trial",

abstract = "PURPOSE: Pemetrexed is a chemotherapeutic drug in the treatment of non-small cell lung cancer and mesothelioma. Optimized dosing of pemetrexed based on renal function instead of body surface area (BSA) is hypothesized to reduce pharmacokinetic variability in systemic exposure and could therefore improve treatment outcomes. The aim of this study is to compare optimized dosing to standard BSA-based dosing.METHODS: A multicenter randomized (1:1) controlled trial was performed to assess superiority of optimized dosing versus BSA-based dosing in patients who were eligible for pemetrexed-based chemotherapy. The individual exposure to pemetrexed in terms of area under the concentration-time curve (AUC) was determined. The fraction of patients attaining to a predefined typical target AUC (164 mg × h/L ± 25%) was calculated.RESULTS: A total of 81 patients were included. Target attainment was not statistically significant different between both arms (89% vs. 84% (p = 0.505)). The AUC of pemetrexed was similar between the optimized dosing arm (n = 37) and the standard of care arm (n = 44) (155 mg × h/L vs 160 mg × h/L (p = 0.436).CONCLUSION: We could not show superiority of optimized dosing of pemetrexed in patients with an adequate renal function does not show added value on the attainment of a pharmacokinetic endpoint, safety, nor QoL compared to standard of care dosing.CLINICAL TRIAL NUMBER: Clinicaltrials.gov identifier: NCT03655821.",

author = "{de Rouw}, Nikki and Boosman, {Ren{\'e} J} and Burgers, {Jacobus A} and Huitema, {Alwin D R} and Dingemans, {Anne-Marie C} and Derijks, {Hieronymus J} and Burger, {David M} and Berber Piet and Hendriks, {Lizza E L} and Bonne Biesma and Pruis, {Melinda A} and Dumoulin, {Daphne W} and Sander Croes and Mathijssen, {Ron H J} and {van den Heuvel}, {Michel M} and {Ter Heine}, Rob",

note = "{\textcopyright} 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.",

year = "2023",

month = jan,

doi = "10.1007/s00280-022-04489-1",

language = "English",

volume = "91",

pages = "33--42",

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publisher = "Springer Verlag",

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de Rouw, N, Boosman, RJ, Burgers, JA, Huitema, ADR, Dingemans, A-MC, Derijks, HJ, Burger, DM, Piet, B, Hendriks, LEL, Biesma, B, Pruis, MA, Dumoulin, DW, Croes, S, Mathijssen, RHJ, van den Heuvel, MM & Ter Heine, R 2023, 'Renal function-based versus standard dosing of pemetrexed: a randomized controlled trial', Cancer Chemotherapy and Pharmacology, vol. 91, no. 1, pp. 33-42. https://doi.org/10.1007/s00280-022-04489-1

TY - JOUR

T1 - Renal function-based versus standard dosing of pemetrexed

T2 - a randomized controlled trial

AU - de Rouw, Nikki

AU - Boosman, René J

AU - Burgers, Jacobus A

AU - Huitema, Alwin D R

AU - Dingemans, Anne-Marie C

AU - Derijks, Hieronymus J

AU - Burger, David M

AU - Piet, Berber

AU - Hendriks, Lizza E L

AU - Biesma, Bonne

AU - Pruis, Melinda A

AU - Dumoulin, Daphne W

AU - Croes, Sander

AU - Mathijssen, Ron H J

AU - van den Heuvel, Michel M

AU - Ter Heine, Rob

PY - 2023/1

Y1 - 2023/1

N2 - PURPOSE: Pemetrexed is a chemotherapeutic drug in the treatment of non-small cell lung cancer and mesothelioma. Optimized dosing of pemetrexed based on renal function instead of body surface area (BSA) is hypothesized to reduce pharmacokinetic variability in systemic exposure and could therefore improve treatment outcomes. The aim of this study is to compare optimized dosing to standard BSA-based dosing.METHODS: A multicenter randomized (1:1) controlled trial was performed to assess superiority of optimized dosing versus BSA-based dosing in patients who were eligible for pemetrexed-based chemotherapy. The individual exposure to pemetrexed in terms of area under the concentration-time curve (AUC) was determined. The fraction of patients attaining to a predefined typical target AUC (164 mg × h/L ± 25%) was calculated.RESULTS: A total of 81 patients were included. Target attainment was not statistically significant different between both arms (89% vs. 84% (p = 0.505)). The AUC of pemetrexed was similar between the optimized dosing arm (n = 37) and the standard of care arm (n = 44) (155 mg × h/L vs 160 mg × h/L (p = 0.436).CONCLUSION: We could not show superiority of optimized dosing of pemetrexed in patients with an adequate renal function does not show added value on the attainment of a pharmacokinetic endpoint, safety, nor QoL compared to standard of care dosing.CLINICAL TRIAL NUMBER: Clinicaltrials.gov identifier: NCT03655821.

AB - PURPOSE: Pemetrexed is a chemotherapeutic drug in the treatment of non-small cell lung cancer and mesothelioma. Optimized dosing of pemetrexed based on renal function instead of body surface area (BSA) is hypothesized to reduce pharmacokinetic variability in systemic exposure and could therefore improve treatment outcomes. The aim of this study is to compare optimized dosing to standard BSA-based dosing.METHODS: A multicenter randomized (1:1) controlled trial was performed to assess superiority of optimized dosing versus BSA-based dosing in patients who were eligible for pemetrexed-based chemotherapy. The individual exposure to pemetrexed in terms of area under the concentration-time curve (AUC) was determined. The fraction of patients attaining to a predefined typical target AUC (164 mg × h/L ± 25%) was calculated.RESULTS: A total of 81 patients were included. Target attainment was not statistically significant different between both arms (89% vs. 84% (p = 0.505)). The AUC of pemetrexed was similar between the optimized dosing arm (n = 37) and the standard of care arm (n = 44) (155 mg × h/L vs 160 mg × h/L (p = 0.436).CONCLUSION: We could not show superiority of optimized dosing of pemetrexed in patients with an adequate renal function does not show added value on the attainment of a pharmacokinetic endpoint, safety, nor QoL compared to standard of care dosing.CLINICAL TRIAL NUMBER: Clinicaltrials.gov identifier: NCT03655821.

U2 - 10.1007/s00280-022-04489-1

DO - 10.1007/s00280-022-04489-1

M3 - Article

C2 - 36413252

SN - 0344-5704

VL - 91

SP - 33

EP - 42

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

IS - 1

ER -