N de Rouw1, R J Boosman2, H van de Bruinhorst3, B Biesma4, M M van den Heuvel5, D M Burger6, L B Hilbrands7, R Ter Heine6, H J Derijks8. 1. Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Pharmacy, Nijmegen, The Netherlands; Jeroen Bosch Hospital, Department of Pharmacy, 's-Hertogenbosch, The Netherlands. Electronic address: Nikki.derouw@radboudumc.nl. 2. Antoni van Leeuwenhoek - The Netherlands Cancer Institute, Department of Pharmacy & Pharmacology, Amsterdam, The Netherlands. 3. Utrecht University, School of Pharmacy, Utrecht, The Netherlands. 4. Jeroen Bosch Hospital, Department of Pulmonology, 's-Hertogenbosch, The Netherlands. 5. Radboud University Medical Center, Department of Pulmonology, Nijmegen, The Netherlands. 6. Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Pharmacy, Nijmegen, The Netherlands. 7. Radboud University Medical Center, Department of Nephrology, Nijmegen, The Netherlands. 8. Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Pharmacy, Nijmegen, The Netherlands; Jeroen Bosch Hospital, Department of Pharmacy, 's-Hertogenbosch, The Netherlands.
Abstract
INTRODUCTION: Pemetrexed is a pharmacotherapeutic cornerstone in the treatment of non-small cell lung cancer. As it is primarily eliminated by renal excretion, adequate renal function is essential to prevent toxic exposure. There is growing evidence for the nephrotoxic potential of pemetrexed, which even becomes a greater issue now combined immuno-chemotherapy prolongs survival. Therefore, the aim of this study was to describe the incidence of nephrotoxicity and related treatment consequences during pemetrexed-based treatment. METHODS: A retrospective cohort study was conducted in the Jeroen Bosch Hospital, Den Bosch, the Netherlands. All patients that received at least 1 cycle of pemetrexed based therapy were included in the dataset. The primary outcome was defined as a ≥25 % reduction in eGFR. Additionally, the treatment consequences of decreased renal function were assessed. Logistic regression was used to identify risk factors for nephrotoxicity during treatment with pemetrexed. RESULTS: Of the 359 patients included in this analysis, 21 % patients had a clinically relevant decline in renal function after treatment and 8.1 % of patients discontinued treatment due to nephrotoxicity. Cumulative dose (≥10 cycles of pemetrexed based therapy) was identified as a risk factor for the primary outcome measure (adjusted OR 5.66 (CI 1.73-18.54)). CONCLUSION: This study shows that patients on pemetrexed-based treatment are at risk of developing renal impairment. Risk significantly increases with prolonged treatment. Renal impairment is expected to become an even greater issue now that pemetrexed-based immuno-chemotherapy results in longer survival and thus longer treatment duration.
INTRODUCTION:Pemetrexed is a pharmacotherapeutic cornerstone in the treatment of non-small cell lung cancer. As it is primarily eliminated by renal excretion, adequate renal function is essential to prevent toxic exposure. There is growing evidence for the nephrotoxic potential of pemetrexed, which even becomes a greater issue now combined immuno-chemotherapy prolongs survival. Therefore, the aim of this study was to describe the incidence of nephrotoxicity and related treatment consequences during pemetrexed-based treatment. METHODS: A retrospective cohort study was conducted in the Jeroen Bosch Hospital, Den Bosch, the Netherlands. All patients that received at least 1 cycle of pemetrexed based therapy were included in the dataset. The primary outcome was defined as a ≥25 % reduction in eGFR. Additionally, the treatment consequences of decreased renal function were assessed. Logistic regression was used to identify risk factors for nephrotoxicity during treatment with pemetrexed. RESULTS: Of the 359 patients included in this analysis, 21 % patients had a clinically relevant decline in renal function after treatment and 8.1 % of patients discontinued treatment due to nephrotoxicity. Cumulative dose (≥10 cycles of pemetrexed based therapy) was identified as a risk factor for the primary outcome measure (adjusted OR 5.66 (CI 1.73-18.54)). CONCLUSION: This study shows that patients on pemetrexed-based treatment are at risk of developing renal impairment. Risk significantly increases with prolonged treatment. Renal impairment is expected to become an even greater issue now that pemetrexed-based immuno-chemotherapy results in longer survival and thus longer treatment duration.
Authors: Nikki de Rouw; Berber Piet; Hieronymus J Derijks; Michel M van den Heuvel; Rob Ter Heine Journal: Drug Saf Date: 2021-11-06 Impact factor: 5.606
Authors: Nikki de Rouw; Merel de Boer; René J Boosman; Michel M van den Heuvel; David M Burger; Joris E Lieverse; Hieronymus J Derijks; Geert W J Frederix; Rob Ter Heine Journal: Clin Pharmacol Ther Date: 2022-02-21 Impact factor: 6.903