Background: In high-dose methotrexate (HD-MTX) therapy, delayed elimination of MTX from plasma leads to severe adverse effects. However, the risk factors for the delayed elimination of plasma MTX are still unclear.
Objective: The purpose of this study was to investigate the factors related to the delayed MTX elimination in HD-MTX monotherapy.
Methods: This retrospective study was performed on patients who received HD-MTX monotherapy between April 2009 and March 2019 at the Hiroshima University Hospital. Patients were divided into a "Normal" and a "Delayed" group according to their MTX plasma concentration at 48 or 72 hours after administration. Patient characteristics, dose of HD-MTX, MTX plasma concentration, and adverse effects were analyzed and compared between the 2 groups.
Results: A total of 74 patients were included in this study. Logistic analysis of patient baseline characteristics was performed to identify risk factors for delayed MTX elimination. Serum albumin (ALB) was detected as a risk factor. Univariate and multivariate analysis revealed that low ALB level (<3.7 g/dL) and type of cancer were associated with delayed MTX elimination (univariate analysis: odds ratio [OR] = 6.00, = 0.004, and OR = 4.33, = 0.039, respectively; multivariate analysis: adjusted OR [AOR] = 6.45, = 0.006, and AOR = 8.11, = 0.018, respectively). Adverse effects were not significantly different between the 2 groups, excluding renal impairment.
Conclusions And Relevance: Our study showed that low ALB is a risk factor for delayed MTX elimination in HD-MTX monotherapy. Pharmacokinetic analysis is needed to establish the dose of HD-MTX in patients with a low ALB level.
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