Methotrexate Management in Chemotherapy

Introduction to Methotrexate Management

• The National Comprehensive Cancer Network recommends both leucovorin rescue and urine alkalinization as essential strategies for reducing methotrexate levels and preventing toxicity during high-dose methotrexate chemotherapy regimens 1

Leucovorin Rescue Effect on Methotrexate Levels

• Leucovorin (folinic acid) rescue is mandatory when administering high-dose methotrexate (3-8 g/m²) to prevent life-threatening toxicity by providing reduced folates that bypass methotrexate's inhibition of dihydrofolate reductase 2, 1

Monitoring and Adjusting Therapy

• If methotrexate levels remain high despite standard measures, treatment with carboxypeptidase G2 should be considered 1
• For patients with prolonged high levels of methotrexate who require additional cycles, methylene-tetrahydrofolate reductase (MTHFR) genotyping is recommended to identify individuals at increased risk of toxicity 1