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 journalArticleAcademicpeer-review

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

Original languageEnglish
Pages (from-to)33-42
Number of pages10
JournalCancer Chemotherapy and Pharmacology
Volume91
Issue number1
DOIs
Publication statusE-pub ahead of print - 21 Nov 2022

Bibliographical note

Funding Information:
Our research was funded by ZonMw (project number: 848016010).

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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