CNS lymphoma

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EORTC-BTG Protocol 26952

Induction phase

• Methotrexate (MTX) 1000 mg/m2 IV on days 1, 10, 20
• Lomustine (Ceenu) 40 mg/m2 PO on day 1
• Procarbazine (Matulane) 60 mg/m2 PO daily on days 1 through 7
• Methylprednisolone (Solumedrol) 120 mg/m2 PO/IV every other day from days 1 through 20, and 60 mg/m2 days 20 through 45
• Methotrexate (MTX) 15 mg IT (admixed with cytarabine) on days 1, 5, 10, 15
• Cytarabine (Cytosar) 40 mg IT (admixed with methotrexate) on days 1, 5, 10, 15
• Folinic acid (Leucovorin) 25 mg PO every 6 hours for 3 days, initiated 24 hours after IV MTX administrations, and 10 mg PO every 6 hours for 2 days after IT MTX administrations

45 days, those with PR or CR proceed to:

Maintenance phase

• Methotrexate (MTX) 1000 mg/m2 IV on day 1
• Lomustine (Ceenu) 40 mg/m2 PO on day 1
• Procarbazine (Matulane) 60 mg/m2 PO daily on days 1 through 7
• Methotrexate (MTX) 15 mg IT (admixed with cytarabine) on day 1
• Cytarabine (Cytosar) 40 mg IT (admixed with methotrexate) on day 1
• Folinic acid (Leucovorin) 25 mg PO every 6 hours for 3 days, initiated 24 hours after IV MTX administration

6-week cycles x 5 cycles

References

1. Hoang-Xuan K, Taillandier L, Chinot O, Soubeyran P, Bogdhan U, Hildebrand J, Frenay M, De Beule N, Delattre JY, Baron B; European Organization for Research and Treatment of Cancer Brain Tumor Group. Chemotherapy alone as initial treatment for primary CNS lymphoma in patients older than 60 years: a multicenter phase II study (26952) of the European Organization for Research and Treatment of Cancer Brain Tumor Group. J Clin Oncol. 2003 Jul 15;21(14):2726-31. link to original article contains verified protocol PubMed

High-dose Methotrexate (MTX) & Ifosfamide

Regimen

• Methotrexate (MTX) 4000 mg/m2 IV over 4 hours on day 1
• Ifosfamide (Ifex) 1500-2000 mg/m2 IV over 3 hours on days 3-5
• Mesna (Mesnex) for prophylaxis of hemorrhagic cystitis
• Folinic acid (Leucovorin) rescue starting 24 hours after start of methotrexate infusion
• Sodium bicarbonate via IV fluid or PO routes used for urine alkalinization to maintain urine pH of at least 8
• Check methotrexate levels 24, 48, and 72 hours after completion of methotrexate infusion.

Methotrexate (MTX) dose adjusted for creatinine clearances <100 mL/min according to the following formula:

• Dose of methotrexate = (creatinine clearance/100) x 4000 mg/m2; the paper did not specify what method was used for calculating creatinine clearance. Patients with creatinine clearance <50 mL/min were excluded from the study.

up to 8 cycles (reference did not list timing/criteria to be used for next cycle of therapy)

• Example orders for High-dose Methotrexate (MTX) & Ifosfamide in lymphoma

References

1. Fischer L, Korfel A, Kiewe P, Neumann M, Jahnke K, Thiel E. Systemic high-dose methotrexate plus ifosfamide is highly effective for central nervous system (CNS) involvement of lymphoma. Ann Hematol. 2009 Feb;88(2):133-9. Epub 2008 Aug 5. link to original article contains verified protocol PubMed