The interest of therapeutic and pharmacological drug monitoring of methotrexate: A systematic review

Semin Oncol. 2025 Apr;52(2):152342. doi: 10.1016/j.seminoncol.2025.152342. Epub 2025 Apr 16.

Abstract

Methotrexate (MTX) is largely prescribed for cancers, particularly hematological malignancies. To reduce its toxicity, therapeutic drug monitoring (TDM) is highly recommended. This review aimed to assess knowledge on methotrexate monitoring and compare strategies for managing its toxicities. We searched several databases for articles that met the selection criteria. All articles were screened and data on analytical methods, results, and toxicities were extracted. Thirty articles were included in this review, consisting mainly of single-center studies. MTX monitoring studies have been conducted in various countries. Patient demographics covered children and adults, with one study focusing on elderly patients. MTX doses varied primarily between high-dose regimens. Sample collection times were varied. Various techniques were used to quantify MTX levels. This review highlights the diversity of study designs, patient populations, dosing regimens, and analytical techniques, emphasizing the need for standardized protocols and further research to optimize MTX treatment, ensuring both efficacy and safety.

Keywords: Hematological malignancies; Methotrexate; Therapeutic drug monitoring; Toxicity.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Antimetabolites, Antineoplastic* / administration & dosage
  • Antimetabolites, Antineoplastic* / adverse effects
  • Antimetabolites, Antineoplastic* / pharmacokinetics
  • Antimetabolites, Antineoplastic* / therapeutic use
  • Drug Monitoring* / methods
  • Humans
  • Methotrexate* / administration & dosage
  • Methotrexate* / adverse effects
  • Methotrexate* / pharmacokinetics
  • Methotrexate* / therapeutic use
  • Neoplasms* / drug therapy

Substances

  • Methotrexate
  • Antimetabolites, Antineoplastic