A European consensus recommendation on the management of delayed methotrexate elimination: supportive measures, leucovorin rescue and glucarpidase treatment.

Christopher P Fox, Carmelo Rizzari, Stefan Schwartz, Pier Luigi Zinzani, Stefan S Bielack, Carole Soussain, Caroline Houillier, Thais Murciano, Wendy Osborne

Journal: Journal of cancer research and clinical oncology 2024;150(10):441

PMID: 39356310

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Abstract

High-dose methotrexate (HDMTX) is used in the treatment of a range of adult and childhood cancers. Although HDMTX can provide effective anti-tumor activity with an acceptable safety profile for most patients, delayed methotrexate elimination (DME) develops in a minority of patients receiving HDMTX and may be accompanied by renal dysfunction and potentially life-threatening toxicity. A panel of European physicians with experience in the use of HDMTX as well as of glucarpidase convened to develop a series of consensus statements to provide practical guidance on the prevention and treatment of DME, including the use of glucarpidase. Robust implementation of supportive measures including hyperhydration and urine alkalinization emerged as critical in order to reduce the risk of DME with HDMTX treatment, with leucovorin rescue critical in reducing the risk of DME complications. Early recognition of DME is important to promptly implement appropriate treatment including, intensified hydration, high-dose leucovorin and, when appropriate, glucarpidase.

Address: Paediatrics 5 (Oncology, Haematology, Immunology), Klinikum Stuttgart - Olgahospital, Stuttgart Cancer Centre, Stuttgart, Germany.; Service d'Hématologie, Institut Curie, Paris, France.; School of Medicine, University of Nottingham, Nottingham, UK.; Department of Neurooncology, IHU, ICM, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, France.; Pediatric Oncology and Hematology Service, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.; Department of Haematology, Newcastle Upon Tyne NHS Foundation Trust, and Newcastle University, Newcastle Upon Tyne, UK.; Istituto di Ematologia "Seràgnoli", IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.; Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy.; Department of Pediatrics, Foundation IRCCS San Gerardo dei Tintori, Monza, Italy.; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.; Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität and Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany. [email protected].

DOI: 10.1007/s00432-024-05945-6

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MeSH Terms: Humans, Methotrexate, gamma-Glutamyl Hydrolase, Leucovorin, Antimetabolites, Antineoplastic, Consensus, Europe, Neoplasms, Recombinant Proteins