CNS lymphoma

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Untreated

EORTC-BTG Protocol 26952

Regimen

Level of Evidence: Phase II

Induction phase

• Methotrexate (MTX) 1000 mg/m2 IV once on days 1, 10, 20
• Lomustine (Ceenu) 40 mg/m2 PO once on day 1
• Procarbazine (Matulane) 60 mg/m2 PO daily on days 1 to 7
• Methylprednisolone (Solumedrol) 120 mg/m2 PO/IV every other day from days 1 to 20, and 60 mg/m2 days 20 to 45
• Methotrexate (MTX) 15 mg IT (admixed with cytarabine) once on days 1, 5, 10, 15
• Cytarabine (Cytosar) 40 mg IT (admixed with methotrexate) once 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 once on day 1
• Lomustine (Ceenu) 40 mg/m2 PO once on day 1
• Procarbazine (Matulane) 60 mg/m2 PO once daily on days 1 to 7
• Methotrexate (MTX) 15 mg IT (admixed with cytarabine) once on day 1
• Cytarabine (Cytosar) 40 mg IT (admixed with methotrexate) once 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

MT-R

Regimen, Rubenstein, et al. 2013 (CALGB 50202)

Level of Evidence: Phase II

Induction phase

• Methotrexate (MTX) 8000 mg/m2 IV once over 4 hours on day 1
  • Given for a total of 7 doses.
• Folinic acid (Leucovorin) 100 mg/m2 IV every 6 hours, start on day 2, continue until MTX level <0.05
• Rituximab (Rituxan) 375 mg/m2 IV once on day 3
  • Rituximab omitted for T-cell PCNSL and given for a total of 6 doses in all others.
• Temozolomide (Temodar) 150 mg/m2 PO once per day on days 7 to 11 (odd cycles only)

14-day cycles x 8 cycles

Patients achieving CR or CRu were given one additional cycle of methotrexate & temozolomide, followed by consolidation therapy:

Consolidation

• Etoposide (Vepesid) 40 mg/kg IV continuous infusion over 96 hours, days 1 to 4
• Cytarabine (Cytosar) 2 gm/m2 IV Q12H over 2 hours × 8 doses, days 1 to 4

One course

References

1. Rubenstein JL, Hsi ED, Johnson JL, Jung SH, Nakashima MO, Grant B, Cheson BD, Kaplan LD. Intensive Chemotherapy and Immunotherapy in Patients With Newly Diagnosed Primary CNS Lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol. 2013 Jul 1. [Epub ahead of print] link to original article contains verified protocol PubMed

Relapsed/refractory

High-dose Methotrexate (MTX) & Ifosfamide

Regimen

Level of Evidence: Retrospective

• Methotrexate (MTX) 4000 mg/m2 IV over 4 hours once on day 1
• Ifosfamide (Ifex) 1500-2000 mg/m2 IV over 3 hours once daily on days 3 to 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