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Early and excessive leucovorin rescue in the prevention of toxicities after intermediate-dose methotrexate: A cross-sectional study

Redouane Amine Cherif, Lyèce Yargui, Malika Nawel Bouaicha, Hanane Boukrous, Mahdia Saidi, Yamina Ouarhlent.


Background: Due to the lack of methotrexate (MTX) therapeutic monitoring in some hospitals, clinicians often resort to fixed and higher leucovorin (LCV) doses after intermediate-dose MTX (IDMTX) infusion to prevent toxicities’ occurrence. A decision that can lead to the inhibition of MTX action or even helps cancer cells to regenerate.

Aims and Objectives: In view of the risks incurred by patients, a study was carried out to determine whether an early and excessive LCV rescue really avoids the occurrence of toxicities after IDMTX infusion and if not, identify the main encountered adverse effects by a clinical and biological monitoring.

Materials and Methods: A cross-sectional study was conducted from November 2014 to February 2016 with a monitoring of clinical data, methotrexatemias, concentrations of biochemical parameters, and a complete blood count. Analyses were performed before the start of the infusion and 24, 48, and 72 h after.

Results: A total of 15 patients were recruited for a total of 23 infusions of MTX at 3 g/m² over 4 h followed by an early and excessive LCV rescue, starting at the 6th h with a cumulative dose of 320 mg/m². Concentrations of MTX lower than 0.05 μmol/L were observed after 72 h in 19 infusions and after 48 h in 11. Six patients experienced toxicities with significantly higher MTX concentrations compared to patients who had no adverse effects.

Conclusion: Despite the early and excessive LCV rescue used during the study, toxicities sometimes fatal, still took place. It is therefore recommended a methotrexatemia monitoring for at least 72 h and an evaluation of the creatinine clearance with neutrophils and lymphocytes numeration whatever the modalities of the rescue.

Key words: Intermediate-dose Methotrexate; Leucovorin; Therapeutic Drug Monitoring

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