{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T02:23:14Z","timestamp":1785810194558,"version":"3.56.0"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:p>Pemetrexed is a cornerstone in chemo(immunotherapy) of non\u2010small cell lung cancer and mesothelioma; however, it is contraindicated in patients with renal impairment due to severe toxicity concerns. Therefore, a large proportion of patients is withheld from effective chemo(immunotherapy). We performed an intra\u2010patient 3\u2009+\u20093 dose escalation renal impairment study (eGFR &lt;\u200945\u2009mL\/min). The pemetrexed dose was calculated based on renal function to reach a target AUC, and patients received oral folinic acid prophylaxis 45\u2009mg four times daily on Days 2\u201315 of each cycle. Endpoints included safety (incidence of hematological and non\u2010hematological toxicity, treatment delays) and pharmacokinetics in line with regulatory guidance for renal impairment trials. Six patients with an estimated glomerular filtration rate (eGFR) between 26 and 41\u2009mL\/min were included. All patients were successfully escalated to the full dose. Adverse event patterns and pharmacokinetics were comparable to those in patients with normal renal function. Grade I\/II anemia occurred in five patients (already present at baseline). One occurrence of grade IV neutropenia was observed, which resolved without intervention. Moreover, in three patients, a 1\u2010week treatment delay occurred. Treatment resulted in a response in four patients (<jats:italic>n<\/jats:italic>\u2009=\u20091 complete response, <jats:italic>n<\/jats:italic>\u2009=\u20092 partial response, <jats:italic>n<\/jats:italic>\u2009=\u20091 stable disease). Pemetrexed can be safely administered in patients with impaired renal function when the dose is calculated based on renal function and folinic acid prophylaxis is administered, thereby enabling an effective treatment modality for patients that, thus far, could not be treated.<\/jats:p>","DOI":"10.1002\/cpt.3735","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T07:24:07Z","timestamp":1748330647000},"page":"715-722","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Folinic Acid Prophylaxis and Dose Adjustments Enable Safe Treatment with Pemetrexed in Patients with Renal Impairment"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1991-0552","authenticated-orcid":false,"given":"Nikki","family":"de Rouw","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy Amphia Hospital  Breda The Netherlands"},{"name":"Department of Pharmacy, Pharmacology &amp; Toxicology Research Institute for Medical Innovation, Radboudumc  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1225-4740","authenticated-orcid":false,"given":"Leila\u2010Sophie","family":"Otten","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmacology &amp; Toxicology Research Institute for Medical Innovation, Radboudumc  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5321-0816","authenticated-orcid":false,"given":"Mart P.","family":"Kicken","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmacology &amp; Toxicology Research Institute for Medical Innovation, Radboudumc  Nijmegen The Netherlands"},{"name":"Department of Clinical Pharmacy Catharina Hospital  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9069-3597","authenticated-orcid":false,"given":"Berber","family":"Piet","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases Research Institute for Medical Innovation, Radboudumc  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5386-170X","authenticated-orcid":false,"given":"Bonne","family":"Biesma","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases Jeroen Bosch Hospital's  Hertogenbosch The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3223-1255","authenticated-orcid":false,"given":"Bianca","family":"van Veggel","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases Jeroen Bosch Hospital's  Hertogenbosch The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8487-9344","authenticated-orcid":false,"given":"Christi M.J.","family":"Steendam","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases Catharina Hospital  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3086-1591","authenticated-orcid":false,"given":"Ben","family":"van den Borne","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases Catharina Hospital  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3521-2535","authenticated-orcid":false,"given":"Lizza E.L.","family":"Hendriks","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases GROW\u2010School for Oncology and Reproduction, Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5799-1415","authenticated-orcid":false,"given":"Sander","family":"Croes","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy &amp; Toxicology CARIM\u2010School for Cardiovascular Disease, Maastricht University Medical Centre  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6105-182X","authenticated-orcid":false,"given":"Anne\u2010Marie C.","family":"Dingemans","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Erasmus MC Cancer Institute, University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5578-7902","authenticated-orcid":false,"given":"Daphne W.","family":"Dumoulin","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Erasmus MC Cancer Institute, University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5667-5697","authenticated-orcid":false,"given":"Ron H.J.","family":"Mathijssen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0218-8436","authenticated-orcid":false,"given":"Jacobus A.","family":"Burgers","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology Antoni Van Leeuwenhoek\u2010The Netherlands Cancer Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1939-4639","authenticated-orcid":false,"given":"Alwin D.R.","family":"Huitema","sequence":"additional","affiliation":[{"name":"Department of Pharmacy &amp; Pharmacology Antoni Van Leeuwenhoek\u2010The Netherlands Cancer Institute  Amsterdam The Netherlands"},{"name":"Department of Clinical Pharmacy Utrecht University Medical Center, Utrecht University  Utrecht The Netherlands"},{"name":"Department of Pharmacology Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1658-3100","authenticated-orcid":false,"given":"Hieronymus J.","family":"Derijks","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Jeroen Bosch Hospital  S\u2010Hertogenbosch The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4389-6420","authenticated-orcid":false,"given":"Maarten J.","family":"Deenen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Catharina Hospital  Eindhoven The Netherlands"},{"name":"Department of Clinical Pharmacy and Toxicology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6372-2153","authenticated-orcid":false,"given":"Michel M.","family":"van den Heuvel","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases Research Institute for Medical Innovation, Radboudumc  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2185-8201","authenticated-orcid":false,"given":"Rob","family":"ter Heine","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmacology &amp; Toxicology Research Institute for Medical Innovation, Radboudumc  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801005"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-008-9123-5"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.00.9720"},{"key":"e_1_2_10_4_1","unstructured":"Eli\u2010Lilly.Alimta \u2013 summary of product characteristics<https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/alimta\u2010epar\u2010product\u2010information_en.pdf>. (2009) Accessed July 24 2024."},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33721"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-021-01135-2"},{"key":"e_1_2_10_7_1","unstructured":"EMA.Guideline on the evaluation of the pharmacokinetics of medicinal products in patients with decreased renal function<https:\/\/www.ema.europa.eu\/en\/evaluation\u2010pharmacokinetics\u2010medicinal\u2010products\u2010patients\u2010decreased\u2010renal\u2010function\u2010scientific\u2010guideline>. (2015) Accessed July 24 2024."},{"key":"e_1_2_10_8_1","unstructured":"FDA.Pharmacokinetics in Patients with Impaired Renal Function \u2013 Study Design Data Analysis and Impact on Dosing \u2013 Guidance for Industry<https:\/\/www.fda.gov\/media\/78573\/download>. 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