Methotrexate elimination and toxicity: MTHFR 677C>T polymorphism in patients with primary CNS lymphoma treated with high-dose methotrexate.

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  • Additional Information
    • Source:
      Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 8307268 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1099-1069 (Electronic) Linking ISSN: 02780232 NLM ISO Abbreviation: Hematol Oncol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Oxford, England : Wiley-Blackwell, c1983-
    • Subject Terms:
      Antimetabolites, Antineoplastic/*toxicity ; Central Nervous System Neoplasms/*complications ; Methotrexate/*toxicity ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; Polymorphism, Genetic/*genetics; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antimetabolites, Antineoplastic/adverse effects ; Central Nervous System Neoplasms/drug therapy ; Female ; Humans ; Male ; Methotrexate/adverse effects ; Middle Aged ; Young Adult
    • Abstract:
      The genetic association of the methylenetetrahydrofolate reductase gene (MTHFR) 677C>T polymorphism with methotrexate (MTX)-associated toxicity has been evaluated and conflicting results have been reported. The substantial heterogeneity of the studied population was suggested to be a possible explanation because ethnicity, MTX dose, coadministered chemotherapeutic agents, and folinate rescue dosage regimen could alter the MTX toxicity profile. The patient population was homogenized by limiting the cancer type to primary central nervous system lymphoma and chemotherapy protocol to a high-dose MTX monotherapy regimen. A total of 111 patients with 402 chemotherapy courses were analyzed. MTHFR 677C>T polymorphism was identified as an independent predictive marker for MTX-associated hematologic toxicity (odds ratio, 2.60; 95% confidence interval, 1.32-5.09; P = .0055). Clinically significant nephrotoxicity occurred in patients without delayed elimination, suggesting roles for factors other than serum MTX levels. MTX-induced hepatotoxicity and oral mucositis occurred independently of plasma MTX levels.
      (Copyright © 2016 John Wiley & Sons, Ltd.)
    • Contributed Indexing:
      Keywords: MTHFR 677C>T polymorphism; high-dose methotrexate; toxicity
    • Accession Number:
      0 (Antimetabolites, Antineoplastic)
      EC 1.5.1.20 (MTHFR protein, human)
      EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
      YL5FZ2Y5U1 (Methotrexate)
    • Publication Date:
      Date Created: 20161027 Date Completed: 20180104 Latest Revision: 20220321
    • Publication Date:
      20231215
    • Accession Number:
      10.1002/hon.2363
    • Accession Number:
      27781293