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

Research output: Contribution to journalArticlepeer-review


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: identifier: NCT03655821
Original languageEnglish
Pages (from-to)33-42
JournalCancer Chemotherapy and Pharmacology
Issue number1
Publication statusPublished - Jan 2023


  • Estimated glomerular filtration rate
  • Non-small cell lung cancer
  • Pemetrexed
  • Pharmacokinetics
  • Precision dosing
  • Humans
  • Lung Neoplasms/drug therapy
  • Carcinoma, Non-Small-Cell Lung/drug therapy
  • Antineoplastic Combined Chemotherapy Protocols
  • Quality of Life
  • Kidney/metabolism


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