Document Type

Article

Publication Date

3-13-2025

Identifier

DOI: 10.1007/s00280-025-04749-w; PMCID: PMC11903593

Abstract

PURPOSE: Folinic acid (FA) rescue protocols to counter the adverse effects of high-dose methotrexate (HDMTX) vary widely, and the risk of over-rescue and potential adverse effects of excessive FA (e.g., hypercalcemia) are under-recognized issues when providing augmented rescue in cases of delayed methotrexate elimination (DME). This opinion summary defines over-rescue, describes its potential adverse impacts, highlights the risk of hypercalcemia associated with excessive FA dosing in patients with acute kidney injury (AKI) from HDMTX, and provides recommendations to improve safety and efficacy of FA rescue in patients receiving HDMTX.

METHODS: A multidisciplinary panel of experts with clinical experience in HDMTX treatment convened in three roundtable meetings to coalesce expert opinion and best published evidence on the pharmacology and clinical effects and interactions of FA and HDMTX.

RESULTS: The type of FA (calcium folinate, calcium levofolinate, sodium levofolinate), dose, and frequency of FA administration may be factors for over-rescue and the development of hypercalcemia due to their respective pharmacokinetic characteristics, especially in cases of DME requiring augmented FA rescue.

CONCLUSION: Clinicians are reminded of the possibility of over-rescue with FA and its impact on subsequent HDMTX courses, types of FA available and their durations of action, and avoid providing too frequent doses. In the setting of AKI and DME requiring high doses of FA, use of sodium levofolinate or calcium levofolinate may be considered to reduce the risk of hypercalcemia associated with calcium folinate.

Journal Title

Cancer chemotherapy and pharmacology

Volume

95

Issue

1

First Page

41

Last Page

41

MeSH Keywords

Humans; Methotrexate; Leucovorin; Hypercalcemia; Acute Kidney Injury; Antimetabolites, Antineoplastic; Dose-Response Relationship, Drug

PubMed ID

40075030

Keywords

Delayed methotrexate elimination; Folinic acid; High-dose methotrexate; Hypercalcemia; Levofolinate; Over-rescue

Comments

RETRACTED ARTICLE:

The Editor-in-Chief has retracted this article because Fig. 1 and its legend contained data that was published without the owner’s permission or the patient’s consent. Figure 1 has now been removed. Jesper Heldrup, Stefan Schwartz, Etienne Chatelut, Miriam Hwang do not agree to this retraction. Archie Bleyer did not state explicitly whether they agree ot this retraction. Brooke Bernhardt agrees to this retraction. Laura Ramsey, Lauren Schaff, Carolina Ten, Martin Guscott and Scott Howard did not respond to correspondence from the Editor about this retraction.

Retraction Note Available Here:

https://link.springer.com/article/10.1007/s00280-025-04798-1

This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Publisher's Link: https://link.springer.com/article/10.1007/s00280-025-04749-w

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