Early Urinary Potassium Level Predicts High-dose Methotrexate Elimination Delay in Primary Central Nervous System Lymphoma

Anticancer Res. 2024 Oct;44(10):4427-4433. doi: 10.21873/anticanres.17272.

Abstract

Background/aim: Treatment of primary central nervous system lymphoma (PCNSL) includes high dose methotrexate-based polychemotherapy (HD-MTX). This study aimed to identify early predictive factors of methotrexate (MTX) delayed elimination.

Patients and methods: We prospectively included all patients with newly-diagnosed PCNSL. Daily serum and urinary creatinine and ionogram were collected. We generated two independent cohorts: a training cohort (TC) and a confirmatory cohort (CC).

Results: We included for analysis 64 cures of HD-MTX (20 patients) in the TC and 59 cures (22 patients) in the CC. Median elimination time of MTX was 95 h and 96 h in the TC and CC, respectively. In multivariate analysis, older age (p=0.004), low Karnofsky Performance Status (p=0.036) and high urinary K+ (p=0.001) were associated with delayed MTX elimination. An optimal cutoff for urinary K+ was defined. In the CC, we confirmed that high urinary K+ (p=0.004) remained associated with delayed MTX elimination.

Conclusion: High urinary K+ may be predictive of delayed MTX elimination in primary central nervous system lymphoma. Its relevance as a decision-making factor needs to be validated in additional prospective studies.

Keywords: PCNSL; Primary central nervous system lymphoma; biomarker; high-dose methotrexate; toxicity.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Central Nervous System Neoplasms* / drug therapy
  • Central Nervous System Neoplasms* / urine
  • Female
  • Humans
  • Lymphoma* / drug therapy
  • Lymphoma* / urine
  • Male
  • Methotrexate* / administration & dosage
  • Methotrexate* / therapeutic use
  • Methotrexate* / urine
  • Middle Aged
  • Potassium* / blood
  • Potassium* / urine
  • Prospective Studies

Substances

  • Methotrexate
  • Potassium
  • Antimetabolites, Antineoplastic