High-dose methotrexate

Frequently used to treat acute lymphoblastic leukemia, CNS lymphoma, osteosarcoma and leptomeningeal cancer.

2-10% of patients experience grade 2 risk greater methotrexate nephrotoxicity.

Grade 3-4 toxicity related to nephrotoxicity varies from 0.6% in osteosarcoma to as high as 4-5% in elderly patients with primary CNS lymphoma.

Precipitation of methotrexate in renal tubules accounts for renal toxicity and this is due to prolonged exposure to toxic blood levels of methotrexate.

Patients must have a GFR greater than 60 mL/min and vigorous intravenous hydration and urine alkalinization to maintain urine pH above 7.

Alkalinizing regimen:Intravenous fluids with 100 meq sodium bicarbonate/L +20 meq KCL/L at 125 mL/hr x 4 hours pre-methotrexate, Plus oral sodium bicarbonate 3000 mg PO q 4 hours until methotrexate level 0.05 micromol/L If pH of urine is less than 7, continue alkalinizing regimen until urine ph greater than or equal to 7 before initiating methotrexate.

Methotrexate up to 8000 mg/m2 day 1 in 1 Liter NS over 4 hours and starting 24 hours after the start of methotrexate 25 mg leucovorin q 6 hours, with the first 4 doses Iv and than POUntil methotrexate level .05 µmol/L.


Post hydration: IV fluids with 100 mEq sodium bicarbonate/L +20 mEq KCl/L at 125 mL/hour for 48 hours after methotrexate.

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