Difference between revisions of "CNS lymphoma"

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===Regimen===
 
===Regimen===
−
Level of Evidence:
 
 
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*[[Procarbazine (Matulane)]] 60 mg/m2 PO once per day on days 1 to 7
 
*[[Procarbazine (Matulane)]] 60 mg/m2 PO once per day 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
 
*[[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
+
Intrathecal component:
−
*[[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
+
*[[Methotrexate (MTX)]] 15 mg IT (admixed with [[Cytarabine (Cytosar)]]) once on days 1, 5, 10, 15
 +
*[[Cytarabine (Cytosar)]] 40 mg IT (admixed with [[Methotrexate (MTX)]]) once on days 1, 5, 10, 15
 +
 
 +
Supportive medications:
 +
*[[Folinic acid (Leucovorin)]] 25 mg PO every 6 hours for 3 days, initiated 24 hours after IV [[Methotrexate (MTX)]] administrations, and 10 mg PO every 6 hours for 2 days after IT [[Methotrexate (MTX)]] administrations
  
 
'''45 days, those with PR or CR proceed to:'''
 
'''45 days, those with PR or CR proceed to:'''
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*[[Lomustine (Ceenu)]] 40 mg/m2 PO once on day 1
 
*[[Lomustine (Ceenu)]] 40 mg/m2 PO once on day 1
 
*[[Procarbazine (Matulane)]] 60 mg/m2 PO once per day on days 1 to 7
 
*[[Procarbazine (Matulane)]] 60 mg/m2 PO once per day 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
+
Intrathecal component:
−
*[[Folinic acid (Leucovorin)]] 25 mg PO every 6 hours for 3 days, initiated 24 hours after IV MTX administration
+
*[[Methotrexate (MTX)]] 15 mg IT (admixed with [[Cytarabine (Cytosar)]]) once on day 1
 +
*[[Cytarabine (Cytosar)]] 40 mg IT (admixed with [[Methotrexate (MTX)]]) once on day 1
 +
 
 +
Supportive medications:
 +
*[[Folinic acid (Leucovorin)]] 25 mg PO every 6 hours for 3 days, initiated 24 hours after IV [[Methotrexate (MTX)]] administration
  
 
'''6-week cycles x 5 cycles'''
 
'''6-week cycles x 5 cycles'''
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===Regimen #1, Batchelor et al. 2003===
 
===Regimen #1, Batchelor et al. 2003===
−
Level of Evidence:
 
 
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===Regimen #2, Ferreri et al. 2009===
 
===Regimen #2, Ferreri et al. 2009===
−
Level of Evidence:
 
 
<span  
 
<span  
 
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style="background:#00CD00;
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===Regimen #3, Herrlinger et al. 2005 (NOA-03)===
 
===Regimen #3, Herrlinger et al. 2005 (NOA-03)===
−
Level of Evidence:
 
 
<span  
 
<span  
 
style="background:#EEEE00;
 
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==High-Dose Methotrexate & Cytarabine==
 
==High-Dose Methotrexate & Cytarabine==
−
===Regime, Ferreri et al. 2009===
+
===Regimen, Ferreri et al. 2009===
−
Level of Evidence:
 
 
<span  
 
<span  
 
style="background:#00CD00;
 
style="background:#00CD00;
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===Regimen, DeAngelis et al. 2002 (RTOG 93-10)===
 
===Regimen, DeAngelis et al. 2002 (RTOG 93-10)===
−
Level of Evidence:
 
 
<span  
 
<span  
 
style="background:#EEEE00;
 
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*[[Methotrexate (MTX)]] 2500 mg/m2 IV once over 2 to 3 hours on day 1
 
*[[Methotrexate (MTX)]] 2500 mg/m2 IV once over 2 to 3 hours on day 1
−
*[[Folinic acid (Leucovorin)]] 20 mg PO every 6 hours x 12 doses, beginning 24 hours after IV MTX administration
+
*[[Procarbazine (Matulane)]] 100 mg/m2 PO once per day on days 1 to 7 of odd cycles (1, 3, 5)
 
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (capped at 2.8 mg) IV on day 1
 
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (capped at 2.8 mg) IV on day 1
−
*[[Procarbazine (Matulane)]] 100 mg/m2 PO once per day on days 1 to 7 of odd cycles (1, 3, 5)
 
−
 
−
*[[Methotrexate (MTX)]] 12 mg IT (via Ommaya) once one week after IV MTX administration
 
−
*[[Folinic acid (Leucovorin)]] 10 mg PO every 6 hours x 8 doses, beginning the evening of IT MTX administration
 
  
−
'''14-day cycles x 5 cycles, accompanied by:'''
+
Intrathecal component:
 +
*[[Methotrexate (MTX)]] 12 mg IT (via Ommaya) once one week after IV [[Methotrexate (MTX)]] administration
 +
*[[Folinic acid (Leucovorin)]] 10 mg PO every 6 hours x 8 doses, beginning the evening of IT [[Methotrexate (MTX)]] administration
  
−
*[[Dexamethasone (Decadron)]] 16 mg PO once per day x 7 days, then 12 mg PO once per day x 7 days, then 8 mg PO once per day x 7 days, then 6 mg PO once per day x 7 days, then 4 mg PO once per day x 7 days, then 2 mg PO once per day x 7 days
+
Supportive medications:
 +
*[[Folinic acid (Leucovorin)]] 20 mg PO every 6 hours x 12 doses, beginning 24 hours after IV [[Methotrexate (MTX)]] administration
 +
*[[Dexamethasone (Decadron)]] 16 mg PO once per day x 7 days, then 12 mg PO once per day x 7 days, then 8 mg PO once per day x 7 days, then 6 mg PO once per day x 7 days, then 4 mg PO once per day x 7 days, then 2 mg PO once per day x 7 days (starts with first cycle)
  
−
'''Followed by:'''
+
'''14-day cycles x 5 cycles, followed by:'''
  
 
*Whole-brain irradiation to 45 Gy in 1.80-Gy fractions or to 36 Gy in 1.20-Gy twice-daily fractions
 
*Whole-brain irradiation to 45 Gy in 1.80-Gy fractions or to 36 Gy in 1.20-Gy twice-daily fractions
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===Regimen, Rubenstein et al. 2013 (CALGB 50202)===
 
===Regimen, Rubenstein et al. 2013 (CALGB 50202)===
−
Level of Evidence:
 
 
<span  
 
<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
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*[[Methotrexate (MTX)]] 8000 mg/m2 IV once over 4 hours on day 1
 
*[[Methotrexate (MTX)]] 8000 mg/m2 IV once over 4 hours on day 1
 
**''Given for a total of 7 doses.''
 
**''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
+
*[[Temozolomide (Temodar)]] 150 mg/m2 PO once per day on days 7 to 11 (odd cycles only)
 
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 3
 
*[[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.''
 
**''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)
+
 
 +
Supportive medications:
 +
*[[Folinic acid (Leucovorin)]] 100 mg/m2 IV every 6 hours, start on day 2, continue until MTX level <0.05
  
 
'''14-day cycles x 8 cycles'''
 
'''14-day cycles x 8 cycles'''
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===Regimen, Shah et al. 2007===
 
===Regimen, Shah et al. 2007===
−
Level of Evidence:
 
 
<span  
 
<span  
 
style="background:#EEEE00;
 
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*[[Rituximab (Rituxan)]] 500 mg/m2 IV once over 5 hours on day 1
 
*[[Rituximab (Rituxan)]] 500 mg/m2 IV once over 5 hours on day 1
 
*[[Methotrexate (MTX)]] 3500 mg/m2 IV once over 2 hours on day 2
 
*[[Methotrexate (MTX)]] 3500 mg/m2 IV once over 2 hours on day 2
−
*[[Folinic acid (Leucovorin)]] 20 to 25 mg every 6 hours for at least 72 hours or until serum MTX level < 1e-8 mg/dL, beginning 24 hours after IV MTX administration
+
*[[Procarbazine (Matulane)]] 100 mg/m2 PO once per day on days 1 to 7 of odd cycles
 
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (capped at 2.8 mg) IV on day 2
 
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (capped at 2.8 mg) IV on day 2
−
*[[Procarbazine (Matulane)]] 100 mg/m2 PO once per day on days 1 to 7 of odd cycles
 
  
 +
Intrathecal component:
 
*[[Methotrexate (MTX)]] 12 mg IT (via Ommaya) once sometime between day 5 and 12 (for patients with positive CSF cytology)
 
*[[Methotrexate (MTX)]] 12 mg IT (via Ommaya) once sometime between day 5 and 12 (for patients with positive CSF cytology)
 +
 +
Supportive medications:
 +
*[[Folinic acid (Leucovorin)]] 20 to 25 mg every 6 hours for at least 72 hours or until serum MTX level < 1e-8 mg/dL, beginning 24 hours after IV [[Methotrexate (MTX)]] administration
  
 
'''14-day cycles x 5 to 7 cycles, followed in 3 to 5 weeks by:'''
 
'''14-day cycles x 5 to 7 cycles, followed in 3 to 5 weeks by:'''
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=Relapsed/refractory=
 
=Relapsed/refractory=
  
−
==High-dose Methotrexate (MTX) & Ifosfamide==
+
==High-dose Methotrexate & Ifosfamide==
 
===Regimen===
 
===Regimen===
−
Level of Evidence:
 
 
<span  
 
<span  
 
style="background:#ff0000;
 
style="background:#ff0000;
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*[[Methotrexate (MTX)]] 4000 mg/m2 IV over 4 hours once on day 1
 
*[[Methotrexate (MTX)]] 4000 mg/m2 IV over 4 hours once on day 1
 
*[[Ifosfamide (Ifex)]] 1500 to 2000 mg/m2 IV over 3 hours once per day on days 3 to 5
 
*[[Ifosfamide (Ifex)]] 1500 to 2000 mg/m2 IV over 3 hours once per day on days 3 to 5
 +
 +
Supportive medications:
 
*[[Mesna (Mesnex)]] for prophylaxis of hemorrhagic cystitis
 
*[[Mesna (Mesnex)]] for prophylaxis of hemorrhagic cystitis
−
*[[Folinic acid (Leucovorin)]] rescue starting 24 hours after start of methotrexate infusion
+
*[[Folinic acid (Leucovorin)]] rescue starting 24 hours after start of [[Methotrexate (MTX)]] infusion
 
*Sodium bicarbonate via IV fluid or PO routes used for urine alkalinization to maintain urine pH of at least 8
 
*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.
+
**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:
 
[[Methotrexate (MTX)]] dose adjusted for creatinine clearances <100 mL/min according to the following formula:

Revision as of 21:30, 17 November 2013

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Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.


Untreated

EORTC-BTG Protocol 26952

Regimen

Phase II

Induction phase

Intrathecal component:

Supportive medications:

45 days, those with PR or CR proceed to:

Maintenance phase

Intrathecal component:

Supportive medications:

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

Regimen #1, Batchelor et al. 2003

Phase II

The full dose of 8000 mg/m2 was only given if CrCl was at least 100. For CrCl less than 100, the dose was reduced by the percentage reduction below 100. For example, a CrCl of 50 would mandate a 50% dose reduction.

Induction phase

14-day cycles until CR or a maximum of 8 cycles

Patients achieving CR proceeded to consolidation:

Consolidation

14-day cycles x 2 cycles, then:

Maintenance

28-day cycles x 11 cycles

Regimen #2, Ferreri et al. 2009

Randomized Phase II, >20 per arm

  • Methotrexate (MTX) 3500 mg/m2 IV once on day 1: first 500 mg/m2 given over 15 minutes, remaining 3000 mg/m2 given over 3 hours

21-day cycles x 4 cycles, followed within 4 weeks by:

  • Whole-brain irradiation 36 Gy (any response) or 40 Gy (stable or progressive disease) plus 9 Gy boost to the tumor bed

Regimen #3, Herrlinger et al. 2005 (NOA-03)

Phase II

This was considered a negative trial by the authors and is included here for historical purposes.

14-day cycles x 6 cycles

Patients intolerant of MTX or not achieving CR after 6 cycles were randomized to WBRT or PCV; see article for details.

References

  1. Batchelor T, Carson K, O'Neill A, Grossman SA, Alavi J, New P, Hochberg F, Priet R. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07. J Clin Oncol. 2003 Mar 15;21(6):1044-9. link to original article contains verified protocol PubMed
  2. Herrlinger U, Küker W, Uhl M, Blaicher HP, Karnath HO, Kanz L, Bamberg M, Weller M; Neuro-Oncology Working Group of the German Society. NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report. Ann Neurol. 2005 Jun;57(6):843-7. link to original article contains verified protocol PubMed
  3. Ferreri AJ, Reni M, Foppoli M, Martelli M, Pangalis GA, Frezzato M, Cabras MG, Fabbri A, Corazzelli G, Ilariucci F, Rossi G, Soffietti R, Stelitano C, Vallisa D, Zaja F, Zoppegno L, Aondio GM, Avvisati G, Balzarotti M, Brandes AA, Fajardo J, Gomez H, Guarini A, Pinotti G, Rigacci L, Uhlmann C, Picozzi P, Vezzulli P, Ponzoni M, Zucca E, Caligaris-Cappio F, Cavalli F; International Extranodal Lymphoma Study Group (IELSG). High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet. 2009 Oct 31;374(9700):1512-20. Epub 2009 Sep 18. link to original article contains verified protocol PubMed

High-Dose Methotrexate & Cytarabine

Regimen, Ferreri et al. 2009

Randomized Phase II, >20 per arm

21-day cycles x 4 cycles, followed within 4 weeks by:

  • Whole-brain irradiation 36 Gy (any response) or 40 Gy (stable or progressive disease) plus 9 Gy boost to the tumor bed

References

  1. Ferreri AJ, Reni M, Foppoli M, Martelli M, Pangalis GA, Frezzato M, Cabras MG, Fabbri A, Corazzelli G, Ilariucci F, Rossi G, Soffietti R, Stelitano C, Vallisa D, Zaja F, Zoppegno L, Aondio GM, Avvisati G, Balzarotti M, Brandes AA, Fajardo J, Gomez H, Guarini A, Pinotti G, Rigacci L, Uhlmann C, Picozzi P, Vezzulli P, Ponzoni M, Zucca E, Caligaris-Cappio F, Cavalli F; International Extranodal Lymphoma Study Group (IELSG). High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet. 2009 Oct 31;374(9700):1512-20. Epub 2009 Sep 18. link to original article contains verified protocol PubMed

MPV

MPV: Methotrexate, Procarbazine, Vincristine

Regimen, DeAngelis et al. 2002 (RTOG 93-10)

Phase II

Intrathecal component:

Supportive medications:

  • Folinic acid (Leucovorin) 20 mg PO every 6 hours x 12 doses, beginning 24 hours after IV Methotrexate (MTX) administration
  • Dexamethasone (Decadron) 16 mg PO once per day x 7 days, then 12 mg PO once per day x 7 days, then 8 mg PO once per day x 7 days, then 6 mg PO once per day x 7 days, then 4 mg PO once per day x 7 days, then 2 mg PO once per day x 7 days (starts with first cycle)

14-day cycles x 5 cycles, followed by:

  • Whole-brain irradiation to 45 Gy in 1.80-Gy fractions or to 36 Gy in 1.20-Gy twice-daily fractions

References

  1. DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ; Radiation Therapy Oncology Group Study 93-10. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol. 2002 Dec 15;20(24):4643-8. link to original article contains verified protocol PubMed

MT-R

MT-R: Methotrexate, Temozolomide, Rituximab

Regimen, Rubenstein et al. 2013 (CALGB 50202)

Phase II

Induction phase

  • Methotrexate (MTX) 8000 mg/m2 IV once over 4 hours on day 1
    • Given for a total of 7 doses.
  • Temozolomide (Temodar) 150 mg/m2 PO once per day on days 7 to 11 (odd cycles only)
  • 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.

Supportive medications:

14-day cycles x 8 cycles

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

Consolidation

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 Sep 1;31(25):3061-8. Epub 2013 Apr 8 link to original article contains verified protocol PubMed

R-MPV

R-MPV: Rituximab, Methotrexate, Procarbazine, Vincristine

Regimen, Shah et al. 2007

Phase II

Intrathecal component:

  • Methotrexate (MTX) 12 mg IT (via Ommaya) once sometime between day 5 and 12 (for patients with positive CSF cytology)

Supportive medications:

14-day cycles x 5 to 7 cycles, followed in 3 to 5 weeks by:

  • Complete responders: Whole-brain irradiation to 23.4 Gy in 1.80-Gy fractions
  • All others: Whole-brain irradiation to 45 Gy in 1.80-Gy fractions

References

  1. Shah GD, Yahalom J, Correa DD, Lai RK, Raizer JJ, Schiff D, LaRocca R, Grant B, DeAngelis LM, Abrey LE. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2007 Oct 20;25(30):4730-5. Erratum in: J Clin Oncol. 2008 Jan 10;26(2):340. link to original article contains verified protocol PubMed

Relapsed/refractory

High-dose Methotrexate & Ifosfamide

Regimen

Retrospective

Supportive medications:

  • Mesna (Mesnex) for prophylaxis of hemorrhagic cystitis
  • Folinic acid (Leucovorin) rescue starting 24 hours after start of Methotrexate (MTX) 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)

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
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