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Review
. 2024 Oct 2;150(10):441.
doi: 10.1007/s00432-024-05945-6.

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

Stefan S Bielack #  1 , Carole Soussain #  2 , Christopher P Fox #  3 , Caroline Houillier #  4 , Thais Murciano #  5 , Wendy Osborne #  6 , Pier Luigi Zinzani #  7   8 , Carmelo Rizzari #  9   10 , Stefan Schwartz #  11
Affiliations
Review

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

Stefan S Bielack et al. J Cancer Res Clin Oncol. .

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.

Keywords: Carboxypeptidases; Consensus; Delayed methotrexate elimination; Glucarpidase; Methotrexate pharmacokinetics; Methotrexate toxicity.

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Conflict of interest statement

Stefan S. Bielack has participated in advisory boards for Eisa, MAP Biopharma, Roche and Y-mAbs Therapeutics; and, has acted as a consultant for SERB S.A.S.Christopher P. Fox has provided consultancy/participated in advisory boards for AbbVie, AstraZeneca, Atarabio, BMS, GenMab, Gilead/Kite, Incyte, Janssen, Lilly, Morphosys, Ono, Roche, SERB, SOBI and Takeda; has contributed to remunerated educational activities for AbbVie, Kite/Gilead, Incyte, Janssen, Roche and Takeda; has received travel support from Kite/Gilead and Roche; and, has received research funding from BeiGene.Thais Murciano has received speaker fees from Alexion Farma, Amgen and Novartis; has received support for meeting attendance from Novartis; and, has contributed to advisory boards for Amgen, BTG Pharmaceuticals, Novartis and Sobi.Wendy Osborne has contributed to advisory boards from AbbVie, AstraZeneca, Autolus, Beigene, Incyte, Janssen, Kite Gilead, Kyowa Kirin, MSD, Novartis, Roche, Servier, Sobi, Syneos and Takeda; has received speaker fees from AbbVie, AstraZeneca, Incyte, Janssen, Kite Gilead, Kyowa Kirin, Novartis, Pfizer, Roche and Takeda; has received support for meeting attendance from Kite Gilead, Novartis, Roche and Takeda; and, has participated on a data monitoring safety committee for Syneos.Pier Luigi Zinzani has provided consultancy to EUSA Pharma, MSD and Novartis; has participated in speakers’ bureau for AstraZeneca, Beigene, BMS, Celltrion, EUSA Pharma, Gilead, Incyte, Janssen-Cilag, Kyowa Kirin, MSD, Novartis, Roche, Servier and Takeda; and, has contributed to advisory boards for ADC Therapeutics, AstraZeneca, Beigene, BMS, Celltrion, EUSA Pharma, Gilead, Incyte, Janssen-Cilag, Kyowa Kirin, MSD, Novartis, Roche, Sandoz, Secura Bio, Servier and Takeda.Carmelo Rizzari has received honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events, as well as for participating on advisory boards, from Amgen, BTG Specialty Pharmaceuticals, Clinigen and Jazz Pharmaceuticals. Stefan Schwartz has received a study research grant from BTG Specialty Pharmaceuticals; has received speaker honoraria from Amgen and CSi Hamburg; and, has contributed to advisory boards for Amgen, Pfizer and SERB S.A.S.Carole Soussain and Caroline Houillier declare no further conflicts of interest.

References

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