Difference between revisions of "CNS lymphoma"
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====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 2 & 3 | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 2 & 3 | ||
− | *[[Methotrexate (MTX)]] 500 mg/m<sup>2</sup> IV over 15 minutes, then 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1 (total dose per cycle: 3500 mg/m<sup>2</sup>) | + | *[[Methotrexate (MTX)]] 500 mg/m<sup>2</sup> IV over 15 minutes, then 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1 (total dose per cycle: 3500 mg/m<sup>2</sup>) |
+ | ====Targeted therapy==== | ||
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -5 & 0 | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -5 & 0 | ||
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*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 2 & 3 | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 2 & 3 | ||
*[[Thiotepa (Thioplex)]] 30 mg/m<sup>2</sup> IV over 30 minutes once on day 4 | *[[Thiotepa (Thioplex)]] 30 mg/m<sup>2</sup> IV over 30 minutes once on day 4 | ||
+ | ====Targeted therapy==== | ||
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -5 & 0 | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -5 & 0 | ||
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**CrCl greater than 60 mL/min/1.73m<sup>2</sup>: 8000 mg/m<sup>2</sup> IV over 6 hours once on day 1 | **CrCl greater than 60 mL/min/1.73m<sup>2</sup>: 8000 mg/m<sup>2</sup> IV over 6 hours once on day 1 | ||
**CrCl less than 60 mL/min/1.73m<sup>2</sup>: 4000 mg/m<sup>2</sup> IV over 6 hours once on day 1 | **CrCl less than 60 mL/min/1.73m<sup>2</sup>: 4000 mg/m<sup>2</sup> IV over 6 hours once on day 1 | ||
+ | ====Targeted therapy==== | ||
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 8 | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 8 | ||
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**Cycles 2 & 4: 100 mg/m<sup>2</sup> PO once per day on days 8 to 12 | **Cycles 2 & 4: 100 mg/m<sup>2</sup> PO once per day on days 8 to 12 | ||
**Other weeks: omitted | **Other weeks: omitted | ||
+ | ====Targeted therapy==== | ||
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once, 3 days prior to first dose of MTX | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once, 3 days prior to first dose of MTX | ||
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**Cycles 1, 3, 5, 7: 150 mg/m<sup>2</sup> PO once per day on days 7 to 11 | **Cycles 1, 3, 5, 7: 150 mg/m<sup>2</sup> PO once per day on days 7 to 11 | ||
**Cycles 2, 4, 6: omitted | **Cycles 2, 4, 6: omitted | ||
+ | ====Targeted therapy==== | ||
*[[Rituximab (Rituxan)]] as follows: | *[[Rituximab (Rituxan)]] as follows: | ||
**B-cell PCNSL, Cycles 1 to 6: 375 mg/m<sup>2</sup> IV once on day 3 | **B-cell PCNSL, Cycles 1 to 6: 375 mg/m<sup>2</sup> IV once on day 3 | ||
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''This protocol is meant for patients aged 66-75 years.'' | ''This protocol is meant for patients aged 66-75 years.'' | ||
− | ==== | + | ====A cycles==== |
+ | ====Targeted therapy==== | ||
*[[Rituximab (Rituxan)]] as follows: | *[[Rituximab (Rituxan)]] as follows: | ||
**Cycle A1: 375 mg/m<sup>2</sup> IV once on day 1 | **Cycle A1: 375 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once on day 1 | *[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Ifosfamide (Ifex)]] as follows: | *[[Ifosfamide (Ifex)]] as follows: | ||
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''This protocol is meant for patients aged 18 to 65 years.'' | ''This protocol is meant for patients aged 18 to 65 years.'' | ||
− | ==== | + | ====A cycles==== |
+ | ====Targeted therapy==== | ||
*[[Rituximab (Rituxan)]] as follows: | *[[Rituximab (Rituxan)]] as follows: | ||
**Cycle A1: 375 mg/m<sup>2</sup> IV once on day 1 | **Cycle A1: 375 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 5000 mg/m<sup>2</sup> IV once on day 1 | *[[Methotrexate (MTX)]] 5000 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Ifosfamide (Ifex)]] 800 mg/m<sup>2</sup> IV once per day on days 2 to 5 | *[[Ifosfamide (Ifex)]] 800 mg/m<sup>2</sup> IV once per day on days 2 to 5 | ||
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|} | |} | ||
''Note: this regimen should not be confused with the other R-MCP (rituximab, mitoxantrone, cyclophosphamide, prednisone) used in indolent lymphomas.'' | ''Note: this regimen should not be confused with the other R-MCP (rituximab, mitoxantrone, cyclophosphamide, prednisone) used in indolent lymphomas.'' | ||
+ | ====Targeted therapy==== | ||
+ | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 90 minutes once per day on days -6, 1, 15, 29 | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day on days 2, 16, 30 | *[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day on days 2, 16, 30 | ||
*[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 2 | *[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 2 | ||
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|- | |- | ||
|} | |} | ||
− | ==== | + | ====Targeted therapy==== |
*[[Rituximab (Rituxan)]] as follows: | *[[Rituximab (Rituxan)]] as follows: | ||
**Cycle 1: 375 mg/m<sup>2</sup> IV over 90 minutes once per day on days -6, 1, 15, 29 | **Cycle 1: 375 mg/m<sup>2</sup> IV over 90 minutes once per day on days -6, 1, 15, 29 | ||
**Cycles 2 & 3: 375 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 15, 29 | **Cycles 2 & 3: 375 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 15, 29 | ||
+ | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day on on days 2, 16, 30 | *[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day on on days 2, 16, 30 | ||
*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 2 to 11 | *[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 2 to 11 | ||
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|- | |- | ||
|} | |} | ||
+ | ====Targeted therapy==== | ||
+ | *[[Rituximab (Rituxan)]] 500 mg/m<sup>2</sup> IV over 5 hours once on day 1 | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Methotrexate (MTX)]] 3500 mg/m<sup>2</sup> IV over 2 hours once on day 2 | *[[Methotrexate (MTX)]] 3500 mg/m<sup>2</sup> IV over 2 hours once on day 2 | ||
*[[Procarbazine (Matulane)]] as follows: | *[[Procarbazine (Matulane)]] as follows: | ||
Line 1,813: | Line 1,825: | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | ====Targeted therapy==== |
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | ||
Line 1,860: | Line 1,872: | ||
|} | |} | ||
''This is the dose used in stage 2 of this two-stage protocol.'' | ''This is the dose used in stage 2 of this two-stage protocol.'' | ||
− | ==== | + | ====Targeted therapy==== |
*[[Temsirolimus (Torisel)]] 75 mg IV once per day on days 1, 8, 15, 22 | *[[Temsirolimus (Torisel)]] 75 mg IV once per day on days 1, 8, 15, 22 | ||
Revision as of 20:45, 31 July 2020
Section editors | |||
---|---|---|---|
Seema Nagpal, MD Stanford University Palo Alto, CA |
J.C. Villasboas Bisneto, MD Mayo Clinic Rochester, MN |
42 regimens on this page
60 variants on this page
|
Guidelines
BSH
- 2018: Fox et al. Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma
EANO
- 2015: Hoang-Xuan et al. Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology
ESH
- 2019: Fox et al. Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma
ESMO
- 2016: Vitolo et al. Extranodal diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
GEL/TAMO
- 2016: Peñalver et al. Guidelines for diagnosis, prevention and management of central nervous system involvement in diffuse large B-cell lymphoma patients by the Spanish Lymphoma Group (GELTAMO)
NCCN
CNS prophylaxis, systemic therapy
HiDAC
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HiDAC: High Dose Ara-C (Cytarabine)
Regimen
Study | Evidence |
---|---|
Holte et al. 2013 (CRY-04) | Phase II |
Note: IT treatment was not part of prophylaxis, except that Methotrexate (MTX) 15 mg IT was allowed at time of diagnostic LP.
Preceding treatment
- R-CHOEP-14 x 8
Chemotherapy
- Cytarabine (Ara-C) 3000 mg/m2 IV twice per day on days 1 & 2 (total dose: 12,000 mg/m2)
- Dose reduced to 2000 mg/m2 for patients aged 60 to 65 years
21-day course
Subsequent treatment
References
- CRY-04: Holte H, Leppä S, Björkholm M, Fluge O, Jyrkkiö S, Delabie J, Sundström C, Karjalainen-Lindsberg ML, Erlanson M, Kolstad A, Fosså A, Ostenstad B, Löfvenberg E, Nordström M, Janes R, Pedersen LM, Anderson H, Jerkeman M, Eriksson M; Nordic Lymphoma Group. Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study. Ann Oncol. 2013 May;24(5):1385-92. Epub 2012 Dec 17. link to original article contains verified protocol PubMed NCT01502982
Methotrexate monotherapy
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Regimen
Study | Evidence |
---|---|
Holte et al. 2013 (CRY-04) | Phase II |
Note: IT treatment was not part of prophylaxis, except that Methotrexate (MTX) 15 mg IT was allowed at time of diagnostic LP.
Preceding treatment
Chemotherapy
- Methotrexate (MTX) 3000 mg/m2 IV continuous infusion over 24 hours, started on day 1
Supportive medications
- Folinic acid (Leucovorin) (dose/frequency not specified) starting at 36 hours
One course
References
- CRY-04: Holte H, Leppä S, Björkholm M, Fluge O, Jyrkkiö S, Delabie J, Sundström C, Karjalainen-Lindsberg ML, Erlanson M, Kolstad A, Fosså A, Ostenstad B, Löfvenberg E, Nordström M, Janes R, Pedersen LM, Anderson H, Jerkeman M, Eriksson M; Nordic Lymphoma Group. Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study. Ann Oncol. 2013 May;24(5):1385-92. Epub 2012 Dec 17. link to original article contains verified protocol PubMed NCT01502982
CNS treatment, local therapy
IT Cytarabine monotherapy
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Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Glantz et al. 1999 | Phase III (C) | IT liposomal cytarabine | Inferior ORR |
Chemotherapy, CNS
- Cytarabine (Ara-C) 50 mg IT once per day on days 1, 4, 8, 11, 15, 18, 22, 25
4-week course
Subsequent treatment
- Further therapy was given to responders; see text for details
References
- Glantz MJ, LaFollette S, Jaeckle KA, Shapiro W, Swinnen L, Rozental JR, Phuphanich S, Rogers LR, Gutheil JC, Batchelor T, Lyter D, Chamberlain M, Maria BL, Schiffer C, Bashir R, Thomas D, Cowens W, Howell SB. Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol. 1999 Oct;17(10):3110-6. link to original article contains verified protocol PubMed
IT Cytarabine liposomal monotherapy
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Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Glantz et al. 1999 | Phase III (E-switch-ic) | IT cytarabine | Superior ORR |
Chemotherapy, CNS
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 1
14-day cycle for 2 cycles
Subsequent treatment
- Further therapy was given to responders; see text for details
References
- Glantz MJ, LaFollette S, Jaeckle KA, Shapiro W, Swinnen L, Rozental JR, Phuphanich S, Rogers LR, Gutheil JC, Batchelor T, Lyter D, Chamberlain M, Maria BL, Schiffer C, Bashir R, Thomas D, Cowens W, Howell SB. Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol. 1999 Oct;17(10):3110-6. link to original article contains verified protocol PubMed
Upfront therapy, randomized data
CYM
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CYM: CYtarabine & Methotrexate
Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Ferreri et al. 2009 (IELSG20) | Randomized Phase II, >20 per arm (E-esc) | High-dose MTX | Seems to have superior CR rate |
Ferreri et al. 2016 (IELSG32) | Randomized Phase II (C) | 1. Cytarabine, Methotrexate, Rituximab | Did not meet primary endpoint of CR rate |
2. MATRix | Inferior CR rate |
Chemotherapy
- Cytarabine (Ara-C) 2000 mg/m2 IV over 60 minutes every 12 hours on days 2 & 3
- Methotrexate (MTX) 500 mg/m2 IV over 15 minutes, then 3000 mg/m2 IV over 3 hours once on day 1 (total dose per cycle: 3500 mg/m2)
Supportive medications
- As described in Ferreri et al. 2016:
- Levoleucovorin (Fusilev) 15 mg/m2 IV every 6 hours for 12 doses, beginning 24 hours after the start of Methotrexate (MTX)
- Modifications if MTX level is high 48 hours after the end of the infusion; see paper for details
21-day cycle for 4 cycles
Subsequent treatment
- IELSG20: Whole brain irradiation, within 4 weeks
- IELSG32: Whole brain irradiation versus Carmustine & Thiotepa with auto HSCT
References
- IELSG20: 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. 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
- IELSG32: Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosée PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Rudà R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gørløv JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016 May;3(5):e217-27. Epub 2016 Apr 6. link to original article contains verified protocol PubMed
Cytarabine, Methotrexate, Rituximab
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R-HD-MTX/ARA-C: Rituximab, High-Dose MethoTreXate, ARA-C (Cytarabine)
Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Ferreri et al. 2015 (SCNSL1) | Phase II | ||
Ferreri et al. 2016 (IELSG32) | Randomized Phase II (E-esc) | 1. Cytarabine & Methotrexate | Did not meet primary endpoint of CR rate |
2. MATRix | Seems to have inferior CR rate |
Note: SCNSL1 was intended for secondary CNS lymphoma, whereas IELSG32 was intended for primary CNS lymphoma.
Preceding treatment
- SCNSL1: R-CHOP x 1
Chemotherapy
- Cytarabine (Ara-C) 2000 mg/m2 IV over 60 minutes every 12 hours on days 2 & 3
- Methotrexate (MTX) 500 mg/m2 IV over 15 minutes, then 3000 mg/m2 IV over 3 hours once on day 1 (total dose per cycle: 3500 mg/m2)
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days -5 & 0
CNS therapy
- SCNSL1: Cytarabine liposomal (DepoCyt)
Supportive medications
- Levoleucovorin (Fusilev) 15 mg/m2 IV every 6 hours for 12 doses, beginning 24 hours after the start of Methotrexate (MTX)
- Modifications if MTX level is high 48 hours after the end of the infusion; see paper for details
21-day cycle for 4 cycles
Subsequent treatment
- SCNSL1: Intensification phase (see paper for details)
- IELSG 32: Whole brain irradiation versus Carmustine & Thiotepa with auto HSCT
References
- SCNSL1: Ferreri AJ, Donadoni G, Cabras MG, Patti C, Mian M, Zambello R, Tarella C, Di Nicola M, D'Arco AM, Doa G, Bruno-Ventre M, Assanelli A, Foppoli M, Citterio G, Fanni A, Mulè A, Caligaris-Cappio F, Ciceri F. High doses of antimetabolites followed by high-dose sequential chemoimmunotherapy and autologous stem-cell transplantation in patients with systemic B-cell lymphoma and secondary CNS involvement: Final results of a multicenter phase II trial. J Clin Oncol. 2015 Nov 20;33(33):3903-10. Epub 2015 Aug 17. link to original article PubMed
- IELSG32: Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosée PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Rudà R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gørløv JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016 May;3(5):e217-27. Epub 2016 Apr 6. link to original article contains verified protocol PubMed
MATRix
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MATRix: Methotrexate, Ara-C (Cytarabine), Thiotepa, Rituximab
Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Ferreri et al. 2016 (IELSG32) | Randomized Phase II (E-esc) | 1. Cytarabine & Methotrexate | Superior CR rate |
2. Cytarabine, Methotrexate, Rituximab | Seems to have superior CR rate |
Chemotherapy
- Methotrexate (MTX) 500 mg/m2 IV over 15 minutes, then 3000 mg/m2 IV over 3 hours once on day 1 (total dose per cycle: 3500 mg/m2)
- Cytarabine (Ara-C) 2000 mg/m2 IV over 60 minutes every 12 hours on days 2 & 3
- Thiotepa (Thioplex) 30 mg/m2 IV over 30 minutes once on day 4
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days -5 & 0
Supportive medications
- Levoleucovorin (Fusilev) 15 mg/m2 IV every 6 hours for 12 doses, beginning 24 hours after the start of Methotrexate (MTX)
- Modifications if MTX level is high 48 hours after the end of the infusion; see paper for details
21-day cycle for 4 cycles
Subsequent treatment
References
- IELSG32: Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosée PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Rudà R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gørløv JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016 May;3(5):e217-27. Epub 2016 Apr 6. link to original article contains verified protocol PubMed
MBVP
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MBVP: Methotrexate, BCNU (Carmustine), Vumon (Teniposide), Prednisone
Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Bromberg et al. 2019 (HOVON 105/ALLG NHL 24) | Phase III (C) | R-MBVP | Did not meet primary endpoint of EFS |
Chemotherapy
- Methotrexate (MTX) 3000 mg/m2 IV once per day on days 1 & 15
- Carmustine (BCNU) 100 mg/m2 IV once on day 4
- Teniposide (Vumon) 100 mg/m2 IV once per day on days 2 & 3
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
28-day cycle for 2 cycles
Subsequent treatment
- Responders, all ages: HiDAC consolidation
- Patients younger than 60 also received: low-dose WBRT
References
- HOVON 105/ALLG NHL 24: Bromberg JEC, Issa S, Bakunina K, Minnema MC, Seute T, Durian M, Cull G, Schouten HC, Stevens WBC, Zijlstra JM, Baars JW, Nijland M, Mason KD, Beeker A, van den Bent MJ, Beijert M, Gonzales M, de Jong D, Doorduijn JK; HOVON; ALLG. Rituximab in patients with primary CNS lymphoma (HOVON 105/ALLG NHL 24): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2019 Feb;20(2):216-228. Epub 2019 Jan 7. link to original article contains protocol PubMed
Methotrexate monotherapy
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Regimen variant #1, 3500 mg/m2
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Ferreri et al. 2009 (IELSG20) | Randomized Phase II (C) | High-dose MTX & Cytarabine | Seems to have inferior CR rate |
Chemotherapy
- Methotrexate (MTX) 500 mg/m2 IV over 15 minutes, then 3000 mg/m2 IV over 3 hours once on day 1 (total dose per cycle: 3500 mg/m2)
21-day cycle for 4 cycles
Subsequent treatment
- Whole brain irradiation, within 4 weeks
Regimen variant #2, 4000 mg/m2
Study | Years of enrollment | Evidence |
---|---|---|
Thiel et al. 2010 (G-PCNSL-SG-1) | 2000-2009 | Non-randomized portion of RCT |
All patients received the same induction regimen; however, the induction regimen was changed after 2006 to high-dose MTX & ifosfamide.
Chemotherapy
- Methotrexate (MTX) 4000 mg/m2 IV over 4 hours once on day 1
14-day cycle for 6 cycles
Subsequent treatment
- Patients with CR: whole-brain irradiation versus no further treatment
- Patients with less than CR in the WB-XRT arm: salvage whole-brain irradiation
- Patients with less than CR in the no-WB-XRT: salvage HiDAC
Regimen variant #3, 8000 mg/m2
Study | Evidence |
---|---|
Herrlinger et al. 2005 (NOA-03) | Phase II |
This was considered a negative trial by the authors and is included here for historical purposes.
Chemotherapy
- Methotrexate (MTX) 8000 mg/m2 IV over 4 hours once on day 1
14-day cycle for 6 cycles
Subsequent treatment
- Patients intolerant of MTX or not achieving CR after 6 cycles: salvage whole-brain irradiation versus PCV; see article for details
Regimen variant #4, 8000 mg/m2 with renal adjustment
Study | Evidence |
---|---|
Batchelor et al. 2003 (NABTT 96-07) | Phase II |
Chemotherapy
- Methotrexate (MTX) 8000 mg/m2 IV over 4 hours once on day 1
- The full dose of 8000 mg/m2 was only given if CrCl was at least 100 mL/min/1.73m2. For CrCl less than 100 mL/min/1.73m2, the dose was reduced by the percentage reduction below 100. For example, a CrCl of 50 mL/min/1.73m2 would mandate a 50% dose reduction.
14-day cycle until CR or a maximum of 8 cycles
Subsequent treatment
- Patients achieving CR received two more cycles at the same dose and frequency, then methotrexate maintenance
Regimen variant #5, 12,000 mg/m2
Study | Evidence |
---|---|
Montemurro et al. 2007 (OSHO-53) | Phase II |
This dosing was intended for patients greater than 60 years old.
Chemotherapy
- Methotrexate (MTX) 6000 mg/m2 IV over 4 hours once per day on days 1 & 10
20-day course
Subsequent treatment
- Responders (CR or PR): Bu/TT, then autologous hematopoietic stem cell transplant
Regimen variant #6, 16,000 mg/m2
Study | Evidence |
---|---|
Montemurro et al. 2007 (OSHO-53) | Phase II |
This dosing was intended for patients less than 60 years old.
Chemotherapy
- Methotrexate (MTX) 8000 mg/m2 IV over 4 hours once per day on days 1 & 10
20-day course
Subsequent treatment
- Responders (CR or PR): Bu/TT, then autologous hematopoietic stem cell transplant
References
- NABTT 96-07: 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
- NOA-03: 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 content property of HemOnc.org
- OSHO-53: Montemurro M, Kiefer T, Schüler F, Al-Ali HK, Wolf HH, Herbst R, Haas A, Helke K, Theilig A, Lotze C, Hirt C, Niederwieser D, Schwenke M, Krüger WH, Dölken G. Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study. Ann Oncol. 2007 Apr;18(4):665-71. Epub 2006 Dec 21. link to original article contains verified protocol PubMed
- IELSG20: 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. 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
- G-PCNSL-SG-1: Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, Röth A, Hertenstein B, von Toll T, Hundsberger T, Mergenthaler HG, Leithäuser M, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Plasswilm L, Nägele T, Pietsch T, Bamberg M, Weller M. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010 Nov;11(11):1036-47. Epub 2010 Oct 20. link to original article contains verified protocol PubMed
- Update: Korfel A, Thiel E, Martus P, Möhle R, Griesinger F, Rauch M, Röth A, Hertenstein B, Fischer T, Hundsberger T, Mergenthaler HG, Junghanß C, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Roth P, Bamberg M, Pietsch T, Weller M. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma. Neurology. 2015 Mar 24;84(12):1242-8. Epub 2015 Feb 25. link to original article PubMed
Upfront therapy, non-randomized or retrospective data
Lomustine, Methotrexate, Procarbazine
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MCP: Methotrexate, CCNU (Lomustine), Procarbazine
Regimen
Study | Evidence |
---|---|
Illerhaus et al. 2008a | Phase II |
Chemotherapy
- Lomustine (CCNU) 110 mg/m2 PO once on day 1
- Methotrexate (MTX) 3000 mg/m2 IV over 4 hours once per day on days 1, 15, 30
- Procarbazine (Matulane) 60 mg/m2 PO once per day on days 1 to 10
Supportive medications
- Folinic acid (Leucovorin) 15 mg/m2 (route not specified) every 6 hours beginning 24 hours after start of Methotrexate (MTX) infusion, continued until clearance
45-day cycle for up to 3 cycles
References
- Illerhaus G, Marks R, Müller F, Ihorst G, Feuerhake F, Deckert M, Ostertag C, Finke J. High-dose methotrexate combined with procarbazine and CCNU for primary CNS lymphoma in the elderly: results of a prospective pilot and phase II study. Ann Oncol. 2009 Feb;20(2):319-25. Epub 2008 Oct 26. link to original article contains verified protocol PubMed
Lomustine, Methotrexate, Procarbazine, Methylprednisolone
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Regimen
Study | Evidence |
---|---|
Hoang-Xuan et al. 2003 (EORTC 26952) | Phase II |
This was the first prospective phase II trial evaluating chemotherapy alone in older patients with PCNSL.
Chemotherapy
- Methotrexate (MTX) 1000 mg/m2 IV once per day on days 1, 10, 20
- Lomustine (CCNU) 40 mg/m2 PO once on day 1
- Procarbazine (Matulane) 60 mg/m2 PO once per day on days 1 to 7
- Methylprednisolone (Solumedrol) as follows:
- Days 1 to 20: 120 mg/m2 IV or PO every other day
- Days 20 to 45: 60 mg/m2 IV or PO every other day
Intrathecal chemotherapy
- Methotrexate (MTX) 15 mg IT (admixed with Cytarabine (Ara-C)) once per day on days 1, 5, 10, 15
- Cytarabine (Ara-C) 40 mg IT (admixed with Methotrexate (MTX)) once per day 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-day course
Subsequent treatment
- Patients achieving PR or CR: Lomustine, methotrexate, procarbazine maintenance
References
- EORTC 26952: Hoang-Xuan K, Taillandier L, Chinot O, Soubeyran P, Bogdhan U, Hildebrand J, Frenay M, De Beule N, Delattre JY, Baron B; EORTC 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 Organisation 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
Methotrexate, then Cytarabine
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Protocol
Study | Evidence |
---|---|
Abrey et al. 2003 | Phase II |
Chemotherapy, part 1
- Methotrexate (MTX) 3500 mg/m2 (maximum dose of 7000 mg) IV over 2 hours once on day 1
Supportive medications
- Folinic acid (Leucovorin) 25 mg PO every 6 hours, beginning 24 hours after start of Methotrexate (MTX), continued for 12 doses or until serum MTX level less than 100 nmol/L
14-day cycle for 5 cycles
Patients proceed to part two 72 hours after 5th dose of MTX or once the 5th dose MTX level has cleared:
Chemotherapy, part 2
- Cytarabine (Ara-C) 3000 mg/m2 IV once per day on days 1 & 2
Supportive medications
- Filgrastim (Neupogen) as follows:
- Cycle 1: 10 mcg/kg SC once per day, starting on day 4 and continued until stem cell collection complete
- Cycle 2: 5 mcg/kg SC once per day continued for 2 weeks or until ANC greater than 3000/uL
1-month cycle for 2 cycles (Stem cell collection took place after the first cycle)
Subsequent treatment
References
- Abrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P, Paleologos N, Correa DD, Anderson ND, Caron D, Zelenetz A, Nimer SD, DeAngelis LM. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. J Clin Oncol. 2003 Nov 15;21(22):4151-6. link to original article contains verified protocol PubMed
Methotrexate, then Cytarabine & Thiotepa
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Protocol variant #1
Study | Years of enrollment | Evidence |
---|---|---|
Illerhaus et al. 2006 | 1998-2003 | Phase II |
Chemotherapy, part 1
- Methotrexate (MTX) 8000 mg/m2 IV over 4 hours once per day on days 1, 10, 20
Supportive medications
- Folinic acid (Leucovorin) 15 mg/m2 every 6 hours, beginning 24 hours after start of Methotrexate (MTX), continuing until clearance
28-day course
Patients with CR, PR, or SD "with clinical improvement" after the 2nd dose of MTX proceeded to:
Chemotherapy, stem cell mobilization
- Cytarabine (Ara-C) 3000 mg/m2 IV over 3 hours once per day on days 30 & 31
- Thiotepa (Thioplex) 40 mg/m2 (route not specified) once on day 31
20-day course
Subsequent treatment
Protocol variant #2
Study | Evidence |
---|---|
Illerhaus et al. 2008 | Pilot, <20 patients |
Chemotherapy, part 1
- Methotrexate (MTX) 8000 mg/m2 IV over 4 hours once on day 1
Supportive medications
- Folinic acid (Leucovorin) 15 mg/m2 every 6 hours, beginning 24 hours after start of Methotrexate (MTX), continuing until clearance
10-day cycle for 2 to 4 cycles, followed by:
Chemotherapy, part 2
- Cytarabine (Ara-C) 3000 mg/m2 IV once per day on days 1 & 2
- Thiotepa (Thioplex) 40 mg/m2 (route not specified) once on day 2
21-day cycle for 2 cycles (Stem cells are mobilized and collected after the first cycle)
Subsequent treatment
References
- Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G, Frickhofen N, Feuerhake F, Volk B, Finke J. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3865-70. Epub 2006 Jul 24. link to original article contains verified protocol PubMed
- Update: Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study. Ann Oncol. 2012 Oct;23(10):2670-5. Epub 2012 Apr 3. Erratum in: Ann Oncol. 2015 Mar;26(3):608-11. link to original article PubMed
- Illerhaus G, Müller F, Feuerhake F, Schäfer AO, Ostertag C, Finke J. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica. 2008 Jan;93(1):147-8. link to original article contains verified protocol PubMed
- Update: Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study. Ann Oncol. 2012 Oct;23(10):2670-5. Epub 2012 Apr 3. Erratum in: Ann Oncol. 2015 Mar;26(3):608-11. link to original article PubMed
Methotrexate & Rituximab
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Regimen
Study | Evidence |
---|---|
Chamberlain et al. 2010 | Phase II |
Note: the bounds as described in the paper do not account for the situation where CrCl = 60 mL/min/1.73m2.
Chemotherapy
- Methotrexate (MTX) as follows:
- CrCl greater than 60 mL/min/1.73m2: 8000 mg/m2 IV over 6 hours once on day 1
- CrCl less than 60 mL/min/1.73m2: 4000 mg/m2 IV over 6 hours once on day 1
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 8
14-day cycle for 4 to 6 cycles
Subsequent treatment
- Patients with PR/CR: High-dose methotrexate consolidation
References
- Chamberlain MC, Johnston SK. High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma. Neuro Oncol. 2010 Jul;12(7):736-44. link to original article contains verified protocol link to PMC article PubMed
MPV
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MPV: Methotrexate, Procarbazine, Vincristine
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Abrey et al. 2000 | Non-randomized | |
DeAngelis et al. 2002 (RTOG 93-10) | 1993-NR | Phase II |
Chemotherapy
- Methotrexate (MTX) 2500 mg/m2 IV over 2 to 3 hours once on day 1
- Procarbazine (Matulane) as follows:
- Cycles 1, 3, 5: 100 mg/m2 PO once per day on days 1 to 7
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2.8 mg) IV once on day 1
Intrathecal chemotherapy
- Methotrexate (MTX) 12 mg IT once on day 8 (via Ommaya reservoir)
Supportive medications
- Folinic acid (Leucovorin) as follows:
- 20 mg PO every 6 hours for 12 doses, beginning on day 2; 24 hours after IV Methotrexate (MTX) administration
- 10 mg PO every 6 hours for 8 doses, beginning on day 8, on the evening of IT Methotrexate (MTX) administration
- Dexamethasone (Decadron) as follows:
- Cycle 1: 16 mg PO once per day on days 1 to 7, then 12 mg PO once per day on days 8 to 14
- Cycle 2: 8 mg PO once per day on days 1 to 7, then 6 mg PO once per day on days 8 to 14
- Cycle 3: 4 mg PO once per day on days 1 to 7, then 2 mg PO once per day on days 8 to 14
14-day cycle for 5 cycles
Subsequent treatment
References
- Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol. 2000 Sep;18(17):3144-50. link to original article contains verified protocol PubMed
- Update: Gavrilovic IT, Hormigo A, Yahalom J, DeAngelis LM, Abrey LE. Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2006 Oct 1;24(28):4570-4. link to original article PubMed
- RTOG 93-10: DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ; Radiation Therapy Oncology Group; SWOG. 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
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MT-R: Methotrexate, Temozolomide, Rituximab
Regimen variant #1
Study | Evidence |
---|---|
Glass et al. 2016 (RTOG 0227) | Phase I/II |
This is the MTD of this phase I/II trial; it appears that only a single dose of rituximab was given.
Chemotherapy
- Methotrexate (MTX) 3500 mg/m2 IV once on day 1
- Temozolomide (Temodar) as follows:
- Cycles 2 & 4: 100 mg/m2 PO once per day on days 8 to 12
- Other weeks: omitted
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once, 3 days prior to first dose of MTX
Supportive medications
- Folinic acid (Leucovorin) 25 mg IV every 6 hours, starting 24 hours after Methotrexate (MTX), continue until MTX level less than 100 nmol/L
14-day cycle for 5 cycles
Subsequent treatment
Regimen variant #2
Study | Evidence |
---|---|
Rubenstein et al. 2013 (CALGB 50202) | Phase II |
Chemotherapy
- Methotrexate (MTX) 8000 mg/m2 IV over 4 hours once on day 1
- Temozolomide (Temodar) as follows:
- Cycles 1, 3, 5, 7: 150 mg/m2 PO once per day on days 7 to 11
- Cycles 2, 4, 6: omitted
Targeted therapy
- Rituximab (Rituxan) as follows:
- B-cell PCNSL, Cycles 1 to 6: 375 mg/m2 IV once on day 3
- T-cell PCNSL: omitted
Supportive medications
- Folinic acid (Leucovorin) 100 mg/m2 IV every 6 hours, start on day 2, continue until MTX level less than 50 nmol/L
14-day cycle for 7 cycles
Subsequent treatment
- Patients achieving CR or CRu were given one additional cycle of methotrexate & temozolomide, then CYVE consolidation
References
- 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 link to PMC article PubMed
- Glass J, Won M, Schultz CJ, Brat D, Bartlett NL, Suh JH, Werner-Wasik M, Fisher BJ, Liepman MK, Augspurger M, Bokstein F, Bovi JA, Solhjem MC, Mehta MP. Phase I and II study of induction chemotherapy with methotrexate, rituximab, and temozolomide, followed by whole-brain radiotherapy and postirradiation temozolomide for primary CNS lymphoma: NRG Oncology RTOG 0227. J Clin Oncol. 2016 May 10;34(14):1620-5. Epub 2016 Mar 28. link to original article contains verified protocol link to PMC article PubMed
MVBP
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MVBP: Methotrexate, VP16 (Etoposide), BCNU (Carmustine), MethylPrednisolone
Regimen
Study | Evidence |
---|---|
Colombat et al. 2006 | Phase II |
Chemotherapy
- Methotrexate (MTX) 3000 mg/m2 IV once per day on days 1 & 15
- Etoposide (Vepesid) 100 mg/m2 IV once on day 2
- Carmustine (BCNU) 100 mg/m2 IV once on day 3
- Methylprednisolone (Solumedrol) 60 mg/m2 (route not specified) once per day on days 1 to 5
Supportive medications
- Folinic acid (Leucovorin) details not specified
2 courses (length not specified), separated by 21 days
Intrathecal chemotherapy
- Methotrexate (MTX) 20 mg IT (admixed with Cytarabine (Ara-C) and Methylprednisolone (Solumedrol))
- Cytarabine (Ara-C) 50 mg IT (admixed with Methotrexate (MTX) and Methylprednisolone (Solumedrol))
- Methylprednisolone (Solumedrol) 40 mg IT (admixed with Cytarabine (Ara-C) and Methotrexate (MTX))
6 doses total (timing not specified)
Subsequent treatment
- Responding patients (CR or PR): cytarabine & ifosfamide for stem cell mobilization, then BEAM, then autologous hematopoietic stem cell transplant
- Non-responders: Salvage CYVE
References
- Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broët S, Linassier C, Lamy T; GOELAMS. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. link to original article contains verified protocol PubMed
Nordic Regimen, older patients
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Protocol
Study | Evidence |
---|---|
Pulczynski et al. 2015 (NLGPCNSL) | Phase II |
This protocol is meant for patients aged 66-75 years.
A cycles
Targeted therapy
- Rituximab (Rituxan) as follows:
- Cycle A1: 375 mg/m2 IV once on day 1
Chemotherapy
- Methotrexate (MTX) 3000 mg/m2 IV once on day 1
- Ifosfamide (Ifex) as follows:
- Cycle A1: 800 mg/m2 IV once per day on days 2 to 5
- Dexamethasone (Decadron) 10 mg/m2/day PO on days 2 to 5
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 2
Chemotherapy, B cycles
- Methotrexate (MTX) 5000 mg/m2 IV once on day 1
- Dexamethasone (Decadron) 10 mg/m2/day PO on days 2 to 5
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 2
- Cyclophosphamide (Cytoxan) 150 mg/m2 IV once per day on days 2 to 6
Chemotherapy, C cycles
- Dexamethasone (Decadron) 20 mg/m2/day PO on days 3 to 7
- Cytarabine (Ara-C) 1000 mg/m2 IV every 12 hours on days 1 & 2
- Vindesine (Eldisine) 5 mg IV once on day 1
21-day cycle for 6 cycles (A1, then B1, then C1, then A2, then B2, then C2)
Subsequent treatment
References
- NLGPCNSL: Pulczynski EJ, Kuittinen O, Erlanson M, Hagberg H, Fosså A, Eriksson M, Nordstrøm M, Østenstad B, Fluge Ø, Leppä S, Fiirgaard B, Bersvendsen H, Fagerli UM; Nordic Lymphoma Group. Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by the Nordic Lymphoma Group. Haematologica. 2015 Apr;100(4):534-40. Epub 2014 Dec 5. link to original article contains verified protocol in supplement link to PMC article PubMed
Nordic Regimen, younger patients
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Protocol
Study | Evidence |
---|---|
Pulczynski et al. 2015 (NLGPCNSL) | Phase II |
This protocol is meant for patients aged 18 to 65 years.
A cycles
Targeted therapy
- Rituximab (Rituxan) as follows:
- Cycle A1: 375 mg/m2 IV once on day 1
Chemotherapy
- Methotrexate (MTX) 5000 mg/m2 IV once on day 1
- Ifosfamide (Ifex) 800 mg/m2 IV once per day on days 2 to 5
- Dexamethasone (Decadron) 10 mg/m2/day PO on days 2 to 5
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 2
Chemotherapy, B cycles
- Methotrexate (MTX) 5000 mg/m2 IV once on day 1
- Dexamethasone (Decadron) 10 mg/m2/day PO on days 2 to 5
- Vincristine (Oncovin) 2 mg IV once on day 1
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 2
- Cyclophosphamide (Cytoxan) 200 mg/m2 IV once per day on days 2 to 5
Chemotherapy, C cycles
- Dexamethasone (Decadron) 20 mg/m2/day PO on days 3 to 7
- Cytarabine (Ara-C) 1500 mg/m2 IV every 12 hours on days 1 & 2
- Vindesine (Eldisine) 5 mg IV once on day 1
21-day cycle for 6 cycles (A1, then B1, then C1, then A2, then B2, then C2)
References
- NLGPCNSL: Pulczynski EJ, Kuittinen O, Erlanson M, Hagberg H, Fosså A, Eriksson M, Nordstrøm M, Østenstad B, Fluge Ø, Leppä S, Fiirgaard B, Bersvendsen H, Fagerli UM; Nordic Lymphoma Group. Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by the Nordic Lymphoma Group. Haematologica. 2015 Apr;100(4):534-40. Epub 2014 Dec 5. link to original article contains verified protocol in supplement link to PMC article PubMed
R-MCP (CCNU)
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R-MCP: Rituximab, Methotrexate, CCNU (Lomustine), Procarbazine
Regimen
Study | Evidence |
---|---|
Fritsch et al. 2011 | Phase II |
Note: this regimen should not be confused with the other R-MCP (rituximab, mitoxantrone, cyclophosphamide, prednisone) used in indolent lymphomas.
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV over 90 minutes once per day on days -6, 1, 15, 29
Chemotherapy
- Methotrexate (MTX) 3000 mg/m2 IV over 4 hours once per day on days 2, 16, 30
- Lomustine (CCNU) 110 mg/m2 PO once on day 2
- Procarbazine (Matulane) 60 mg/m2 PO once per day on days 2 to 11
Supportive medications
- Folinic acid (Leucovorin) (dose/route not specified) every 6 hours beginning 24 hours after start of MTX infusion, continued for 3 days or until clearance
43-day cycle for up to 3 cycles
References
- Fritsch K, Kasenda B, Hader C, Nikkhah G, Prinz M, Haug V, Haug S, Ihorst G, Finke J, Illerhaus G. Immunochemotherapy with rituximab, methotrexate, procarbazine, and lomustine for primary CNS lymphoma (PCNSL) in the elderly. Ann Oncol. 2011 Sep;22(9):2080-5. Epub 2011 Feb 8. link to original article contains verified protocol PubMed
R-MP
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R-MP: Rituximab, Methotrexate, Procarbazine
Regimen
Study | Evidence |
---|---|
Fritsch et al. 2016 (PRIMAIN) | Phase II |
Targeted therapy
- Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m2 IV over 90 minutes once per day on days -6, 1, 15, 29
- Cycles 2 & 3: 375 mg/m2 IV over 90 minutes once per day on days 1, 15, 29
Chemotherapy
- Methotrexate (MTX) 3000 mg/m2 IV over 4 hours once per day on on days 2, 16, 30
- Procarbazine (Matulane) 60 mg/m2 PO once per day on days 2 to 11
42-day cycle for 3 cycles
Subsequent treatment
References
- Fritsch K, Kasenda B, Schorb E, Hau P, Bloehdorn J, Möhle R, Löw S, Binder M, Atta J, Keller U, Wolf HH, Krause SW, Heß G, Naumann R, Sasse S, Hirt C, Lamprecht M, Martens U, Morgner A, Panse J, Frickhofen N, Röth A, Hader C, Deckert M, Fricker H, Ihorst G, Finke J, Illerhaus G. High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study). Leukemia. 2017 Apr;31(4):846-852. Epub 2016 Nov 15. link to original article contains verified protocol link to PMC article PubMed
R-MPV
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R-MPV: Rituximab, Methotrexate, Procarbazine, Vincristine
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Shah et al. 2007 | 2002-2005 | Phase II |
Omuro et al. 2015 (MSK 04-129) | Phase II |
Targeted therapy
- Rituximab (Rituxan) 500 mg/m2 IV over 5 hours once on day 1
Chemotherapy
- Methotrexate (MTX) 3500 mg/m2 IV over 2 hours once on day 2
- Procarbazine (Matulane) as follows:
- Odd cycles: 100 mg/m2 PO once per day on days 1 to 7
- Even cycles: omitted
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2.8 mg) IV once on day 2
Intrathecal chemotherapy
- (only described in the Shah et al. 2007 trial)
- 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 less than 100 nmol/L, beginning 24 hours after IV Methotrexate (MTX) administration
14-day cycle for 5 to 7 cycles
Subsequent treatment
- Shah et al. 2007: followed in 3 to 5 weeks by whole-brain irradiation
- Omuro et al. 2015: Bu/TT/Cy, then autologous hematopoietic stem cell transplant, after 5 cycles if CR achieved, or after 7 cycles for PR/CR at that time
References
- 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
- Update: Morris PG, Correa DD, Yahalom J, Raizer JJ, Schiff D, Grant B, Grimm S, Lai RK, Reiner AS, Panageas K, Karimi S, Curry R, Shah G, Abrey LE, DeAngelis LM, Omuro A. Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: final results and long-term outcome. J Clin Oncol. 2013 Nov 1;31(31):3971-9. Epub 2013 Oct 7. link to original article PubMed
- MSK 04-129: Omuro A, Correa DD, DeAngelis LM, Moskowitz CH, Matasar MJ, Kaley TJ, Gavrilovic IT, Nolan C, Pentsova E, Grommes CC, Panageas KS, Baser RE, Faivre G, Abrey LE, Sauter CS. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 2015 Feb 26;125(9):1403-10. Epub 2015 Jan 7. link to original article contains verified protocol link to PMC article PubMed
Consolidation and/or maintenance after upfront therapy
BCNU/TT, then auto HSCT
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BCNU/TT: BCNU (Carmustine), ThioTepa
Regimen variant #1
Study | Years of enrollment | Evidence |
---|---|---|
Illerhaus et al. 2006 | 1998-2003 | Phase II |
Note that the day count starts from the very beginning of treatment.
Preceding treatment
Chemotherapy
- Carmustine (BCNU) 400 mg/m2 IV once on day 50
- Thiotepa (Thioplex) 5 mg/kg (route not specified) once per day on days 51 & 52
Supportive medications
- Granulocyte colony-stimulating factor starting on day 61, continued until WBC greater than 1 x 109/L for 3 days
- "Standard supportive measures were taken according to institutional guidelines."
Stem cells re-infused on day 56
Subsequent treatment
Regimen variant #2
Study | Evidence |
---|---|
Illerhaus et al. 2008 | Pilot, <20 patients |
Preceding treatment
Chemotherapy
- Carmustine (BCNU) 400 mg/m2 IV once on day 1
- Thiotepa (Thioplex) 5 mg/kg (route not specified) twice per day on days 2 & 3
Stem cells re-infused on day 7
References
- Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G, Frickhofen N, Feuerhake F, Volk B, Finke J. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3865-70. Epub 2006 Jul 24. link to original article contains verified protocol PubMed
- Update: Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study. Ann Oncol. 2012 Oct;23(10):2670-5. Epub 2012 Apr 3. Erratum in: Ann Oncol. 2015 Mar;26(3):608-11. link to original article PubMed
- Illerhaus G, Müller F, Feuerhake F, Schäfer AO, Ostertag C, Finke J. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica. 2008 Jan;93(1):147-8. link to original article contains verified protocol PubMed
- Update: Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study. Ann Oncol. 2012 Oct;23(10):2670-5. Epub 2012 Apr 3. Erratum in: Ann Oncol. 2015 Mar;26(3):608-11. link to original article PubMed
- IELSG32: Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosée PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Rudà R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gørløv JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016 May;3(5):e217-27. Epub 2016 Apr 6. link to original article contains verified protocol PubMed
- Update: Ferreri AJM, Cwynarski K, Pulczynski E, Fox CP, Schorb E, La Rosée P, Binder M, Fabbri A, Torri V, Minacapelli E, Falautano M, Ilariucci F, Ambrosetti A, Roth A, Hemmaway C, Johnson P, Linton KM, Pukrop T, Sønderskov Gørløv J, Balzarotti M, Hess G, Keller U, Stilgenbauer S, Panse J, Tucci A, Orsucci L, Pisani F, Levis A, Krause SW, Schmoll HJ, Hertenstein B, Rummel M, Smith J, Pfreundschuh M, Cabras G, Angrilli F, Ponzoni M, Deckert M, Politi LS, Finke J, Reni M, Cavalli F, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group. Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial. Lancet Haematol. 2017 Nov;4(11):e510-e523. Epub 2017 Oct 17. link to original article PubMed
BEAM, then auto HSCT
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BEAM: BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen variant #1
Study | Evidence |
---|---|
Colombat et al. 2006 | Phase II |
Preceding treatment
- MVBP x 2
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day 1
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days 2 to 5
- Cytarabine (Ara-C) 100 mg/m2 IV every 12 hours on days 2 to 5
- Melphalan (Alkeran) 140 mg/m2 IV once on day 6
Day of transplant is not specified
Subsequent treatment
Regimen variant #2
Study | Evidence |
---|---|
Abrey et al. 2003 | Phase II |
Preceding treatment
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -7
- Etoposide (Vepesid) 100 mg/m2 IV every 12 hours on days -6 to -3
- Cytarabine (Ara-C) 200 mg/m2 IV every 12 hours on days -6 to -3
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
Supportive medications
- Filgrastim (Neupogen) 5 mcg/kg SC every 12 hours, starting on day +1 and continued until ANC greater than 1000/uL for 3 days or greater than 10,000/uL for 1 day
Stem cells reinfused on day 0
References
- Abrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P, Paleologos N, Correa DD, Anderson ND, Caron D, Zelenetz A, Nimer SD, DeAngelis LM. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. J Clin Oncol. 2003 Nov 15;21(22):4151-6. link to original article contains verified protocol PubMed
- Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broët S, Linassier C, Lamy T; GOELAMS. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. link to original article contains verified protocol PubMed
Bu/TT, then auto HSCT
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Bu/TT: Busulfan, ThioTepa
Regimen
Study | Evidence |
---|---|
Montemurro et al. 2007 (OSHO-53) | Phase II |
Preceding treatment
Chemotherapy
- Busulfan (Myleran) 4 mg/kg PO four times per day on days -8 to -5
- Thiotepa (Thioplex) 5 mg/kg IV once per day on days -4 & -3
Stem cell re-infusion occurs on day 0
References
- OSHO-53: Montemurro M, Kiefer T, Schüler F, Al-Ali HK, Wolf HH, Herbst R, Haas A, Helke K, Theilig A, Lotze C, Hirt C, Niederwieser D, Schwenke M, Krüger WH, Dölken G. Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study. Ann Oncol. 2007 Apr;18(4):665-71. Epub 2006 Dec 21. link to original article contains verified protocol PubMed
Bu/TT/Cy, then auto HSCT
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Bu/TT/Cy: Busulfan, ThioTepa, Cyclophosphamide
Regimen
Study | Evidence |
---|---|
Omuro et al. 2015 (MSK 04-129) | Phase II |
Preceding treatment
Chemotherapy
- Busulfan (Myleran) 3.2 mg/kg IV once per day on days -6, -5, and -4
- Thiotepa (Thioplex) 250 mg/m2 IV once per day on days -9, -8, and -7
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 and -2
Stem cell re-infusion occurs on day 0
References
- MSK 04-129: Omuro A, Correa DD, DeAngelis LM, Moskowitz CH, Matasar MJ, Kaley TJ, Gavrilovic IT, Nolan C, Pentsova E, Grommes CC, Panageas KS, Baser RE, Faivre G, Abrey LE, Sauter CS. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 2015 Feb 26;125(9):1403-10. Epub 2015 Jan 7. link to original article contains verified protocol link to PMC article PubMed
HiDAC
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HiDAC: High Dose Ara-C (Cytarabine)
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Abrey et al. 2000 | Non-randomized | |
DeAngelis et al. 2002 (RTOG 93-10) | 1993-NR | Phase II |
Time interval of cycles is not explicitly described and is derived from Table 1 in DeAngelis et al. 2002.
Preceding treatment
- Whole-brain irradiation x 45 Gy
Chemotherapy
- Cytarabine (Ara-C) 3000 mg/m2 IV over 3 hours once per day on days 1 & 2
21-day cycle for 2 cycles
References
- Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol. 2000 Sep;18(17):3144-50. link to original article contains verified protocol PubMed
- Update: Gavrilovic IT, Hormigo A, Yahalom J, DeAngelis LM, Abrey LE. Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2006 Oct 1;24(28):4570-4. link to original article PubMed
- RTOG 93-10: DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ; Radiation Therapy Oncology Group; SWOG. 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
CYVE
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CYVE: CYtarabine & VEpesid (Etoposide)
EA: Etoposide & Ara-C (Cytarabine)
Regimen
Study | Evidence |
---|---|
Rubenstein et al. 2013 (CALGB 50202) | Phase II |
Preceding treatment
Chemotherapy
- Cytarabine (Ara-C) 2000 mg/m2 IV over 2 hours every 12 hours on days 1 to 4 (total dose: 16,000 mg/m2)
- Etoposide (Vepesid) 10 mg/kg/day IV continuous infusion over 96 hours, started on day 1 (total dose: 40 mg/kg)
4-day course
References
- CALGB 50202: 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 link to PMC article PubMed
Lomustine, Methotrexate, Procarbazine
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Regimen
Study | Evidence |
---|---|
Hoang-Xuan et al. 2003 (EORTC 26952) | Phase II |
Preceding treatment
Chemotherapy
- Methotrexate (MTX) 1000 mg/m2 IV once on day 1
- Lomustine (CCNU) 40 mg/m2 PO once on day 1
- Procarbazine (Matulane) 60 mg/m2 PO once per day on days 1 to 7
Intrathecal component
- Methotrexate (MTX) 15 mg IT (admixed with Cytarabine (Ara-C)) once on day 1
- Cytarabine (Ara-C) 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
42-day cycle for 5 cycles
References
- Hoang-Xuan K, Taillandier L, Chinot O, Soubeyran P, Bogdhan U, Hildebrand J, Frenay M, De Beule N, Delattre JY, Baron B; EORTC 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 Organisation 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
Methotrexate monotherapy
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Regimen variant #1
Study | Evidence |
---|---|
Chamberlain et al. 2010 | Phase II |
Note: the bounds as described in the paper do not account for the situation where CrCl = 60 mL/min/1.73m2.
Preceding treatment
Chemotherapy
- Methotrexate (MTX) as follows:
- CrCl greater than 60 mL/min/1.73m2: 8000 mg/m2 IV over 6 hours once on day 1
- CrCl less than 60 mL/min/1.73m2: 4000 mg/m2 IV over 6 hours once on day 1
28-day cycle for 4 cycles
Regimen variant #2
Study | Evidence |
---|---|
Batchelor et al. 2003 (NABTT 96-07) | Phase II |
Preceding treatment
Chemotherapy
- Methotrexate (MTX) 8000 mg/m2 IV over 4 hours once on day 1
- The full dose of 8000 mg/m2 was only given if CrCl was at least 100 mL/min/1.73m2. For CrCl less than 100 mL/min/1.73m2, the dose was reduced by the percentage reduction below 100. For example, a CrCl of 50 mL/min/1.73m2 would mandate a 50% dose reduction.
28-day cycle for 11 cycles
References
- 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
- Chamberlain MC, Johnston SK. High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma. Neuro Oncol. 2010 Jul;12(7):736-44. link to original article contains verified protocol link to PMC article PubMed
Procarbazine monotherapy
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Regimen
Study | Evidence |
---|---|
Fritsch et al. 2016 (PRIMAIN) | Phase II |
Preceding treatment
- R-MP x 3
Chemotherapy
- Procarbazine (Matulane) 100 mg PO once per day on days 1 to 5
28-day cycle for 6 cycles
References
- Fritsch K, Kasenda B, Schorb E, Hau P, Bloehdorn J, Möhle R, Löw S, Binder M, Atta J, Keller U, Wolf HH, Krause SW, Heß G, Naumann R, Sasse S, Hirt C, Lamprecht M, Martens U, Morgner A, Panse J, Frickhofen N, Röth A, Hader C, Deckert M, Fricker H, Ihorst G, Finke J, Illerhaus G. High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study). Leukemia. 2017 Apr;31(4):846-852. Epub 2016 Nov 15. link to original article contains verified protocol link to PMC article PubMed
Temozolomide monotherapy
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Regimen variant #1
Study | Evidence |
---|---|
Glass et al. 2016 (RTOG 0227) | Phase I/II |
Preceding treatment
Chemotherapy
- Temozolomide (Temodar) as follows:
- Week 14: 200 mg/m2 PO once per day for 5 days (150 mg/m2 allowed)
- Weeks 18, 22, 26, 30, 34, 38, 42, 46, 50: 200 mg/m2 PO once per day for 5 days
- Other weeks: omitted
Regimen variant #2
Study | Evidence |
---|---|
Pulczynski et al. 2015 (NLGPCNSL) | Phase II |
Preceding treatment
Chemotherapy
- Temozolomide (Temodar) 150 mg/m2/day PO on days 1 to 5
28-day cycle for up to 13 cycles (1 year)
References
- NLGPCNSL: Pulczynski EJ, Kuittinen O, Erlanson M, Hagberg H, Fosså A, Eriksson M, Nordstrøm M, Østenstad B, Fluge Ø, Leppä S, Fiirgaard B, Bersvendsen H, Fagerli UM; Nordic Lymphoma Group. Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by the Nordic Lymphoma Group. Haematologica. 2015 Apr;100(4):534-40. Epub 2014 Dec 5. link to original article contains verified protocol in supplement link to PMC article PubMed
- Glass J, Won M, Schultz CJ, Brat D, Bartlett NL, Suh JH, Werner-Wasik M, Fisher BJ, Liepman MK, Augspurger M, Bokstein F, Bovi JA, Solhjem MC, Mehta MP. Phase I and II study of induction chemotherapy with methotrexate, rituximab, and temozolomide, followed by whole-brain radiotherapy and postirradiation temozolomide for primary CNS lymphoma: NRG Oncology RTOG 0227. J Clin Oncol. 2016 May 10;34(14):1620-5. Epub 2016 Mar 28. link to original article contains verified protocol link to PMC article PubMed
Whole brain irradiation
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WBRT: Whole-Brain Radiation Therapy
Regimen variant #1, 23.4 Gy
Study | Years of enrollment | Evidence |
---|---|---|
Shah et al. 2007 | 2002-2005 | Phase II |
Preceding treatment
- R-MPV x 5 to 7 cycles, with complete response
Radiotherapy
- Whole-brain irradiation to 23.4 Gy in 1.80-Gy fractions
Regimen variant #2, 30 Gy
Study | Evidence |
---|---|
Colombat et al. 2006 | Phase II |
Preceding treatment
- BEAM, then autologous hematopoietic stem cell transplant, with complete response
Radiotherapy
- Whole-brain irradiation to 30 Gy in 1.80-Gy fractions
Regimen variant #3, 30 Gy + 10 Gy boost
Study | Evidence |
---|---|
Colombat et al. 2006 | Phase II |
Preceding treatment
- BEAM, then autologous hematopoietic stem cell transplant, with partial response
Radiotherapy
- Whole-brain irradiation to 30 Gy in 1.80-Gy fractions plus 10 Gy boost to the tumor bed
Regimen variant #4, 36 Gy
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Glass et al. 2016 (RTOG 0227) | Phase I/II | ||
Ferreri et al. 2016 (IELSG32) | Randomized Phase II (C) | BCNU/TT, then auto HSCT | Did not meet primary endpoint of PFS24 (*) |
Note: reported efficacy for IELSG32 is based on the 2017 update.
Preceding treatment
- RTOG 0227: MT-R induction
- IELSG32: Cytarabine & MTX versus Cytarabine, MTX, Rituximab versus MATRix induction, with complete response
Radiotherapy
- Whole-brain irradiation to 36 Gy as follows:
- RTOG 0227: 1.20-Gy twice-per-day fractions on weeks 11 to 13
- IELSG32: 1.80-Gy fractions
Subsequent treatment
- RTOG 0227: Temozolomide consolidation
Regimen variant #5, 36 Gy + 9 Gy boost
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Ferreri et al. 2009 (IELSG20) | Non-randomized portion of RCT | ||
Ferreri et al. 2016 (IELSG32) | Randomized Phase II (C) | BCNU/TT, then auto HSCT | Did not meet primary endpoint of PFS24 (*) |
Note: reported efficacy for IELSG32 is based on the 2017 update.
Preceding treatment
- IELSG20: High-dose methotrexate x 4 versus High-dose methotrexate & cytarabine x 4, with any response
- IELSG32: Cytarabine & MTX versus Cytarabine, MTX, Rituximab versus MATRix induction, with partial response
Radiotherapy
- Whole-brain irradiation to 36 Gy in 1.80-Gy fractions plus 9 Gy boost to the tumor bed
Regimen variant #6, 40 Gy + 9 Gy boost
Study | Evidence |
---|---|
Ferreri et al. 2009 (IELSG20) | Non-randomized portion of RCT |
Preceding treatment
- High-dose methotrexate x 4 versus High-dose methotrexate & cytarabine x 4, with stable or progressive disease
Radiotherapy
- Whole-brain irradiation to 40 Gy in 1.80-Gy fractions plus 9 Gy boost to the tumor bed
Regimen variant #7, 45 Gy
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Abrey et al. 2000 | Non-randomized | |||
DeAngelis et al. 2002 (RTOG 93-10) | 1993-NR | Phase II | ||
Illerhaus et al. 2006 | 1998-2003 | Phase II | ||
Thiel et al. 2010 (G-PCNSL-SG-1) | 2000-2009 | Phase III (E-esc) | No further treatment | Inconclusive whether non-inferior OS |
Shah et al. 2007 | 2002-2005 | Phase II |
Note that the day count in Illerhaus et al. 2006 starts from the very beginning of treatment.
Preceding treatment
- Abrey et al. 2000 & RTOG 93-10: MPV x 5
- Illerhaus et al. 2006: BCNU/TT, then autologous hematopoietic stem cell transplant, with complete response
- Shaw et al. 2007: R-MPV x 5 to 7 cycles, without complete response
- G-PCNSL-SG-1, before 2006: High-dose methotrexate x 6
- G-PCNSL-SG-1, after 2006: High-dose methotrexate & ifosfamide x 6
Radiotherapy
- Whole-brain irradiation to 45 Gy as follows:
- Illerhaus et al. 2006: 1.00-Gy fractions, starting on day 90
- G-PCNSL-SG-1: 1.50-Gy fractions
- Abrey et al. 2000, RTOG 93-10, Shaw et al. 2007: 1.80-Gy fractions
Subsequent treatment
- Abrey et al. 2000 & RTOG 93-10: HiDAC consolidation
Regimen variant #8, 50 Gy
Study | Years of enrollment | Evidence |
---|---|---|
Illerhaus et al. 2006 | 1998-2003 | Phase II |
Note that the day count starts from the very beginning of treatment.
Preceding treatment
- BCNU/TT, then autologous hematopoietic stem cell transplant, with partial response
Radiotherapy
- Whole-brain irradiation to 50 Gy in 1.00-Gy fractions, starting on day 90
References
- Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol. 2000 Sep;18(17):3144-50. link to original article contains verified protocol PubMed
- Update: Gavrilovic IT, Hormigo A, Yahalom J, DeAngelis LM, Abrey LE. Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2006 Oct 1;24(28):4570-4. link to original article PubMed
- RTOG 93-10: DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ; Radiation Therapy Oncology Group; SWOG. 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
- Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G, Frickhofen N, Feuerhake F, Volk B, Finke J. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3865-70. Epub 2006 Jul 24. link to original article contains verified protocol PubMed
- Update: Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study. Ann Oncol. 2012 Oct;23(10):2670-5. Epub 2012 Apr 3. Erratum in: Ann Oncol. 2015 Mar;26(3):608-11. link to original article PubMed
- Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broët S, Linassier C, Lamy T; GOELAMS. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. link to original article contains verified protocol PubMed
- 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
- Update: Morris PG, Correa DD, Yahalom J, Raizer JJ, Schiff D, Grant B, Grimm S, Lai RK, Reiner AS, Panageas K, Karimi S, Curry R, Shah G, Abrey LE, DeAngelis LM, Omuro A. Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: final results and long-term outcome. J Clin Oncol. 2013 Nov 1;31(31):3971-9. Epub 2013 Oct 7. link to original article PubMed
- IELSG20: 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. 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
- G-PCNSL-SG-1: Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, Röth A, Hertenstein B, von Toll T, Hundsberger T, Mergenthaler HG, Leithäuser M, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Plasswilm L, Nägele T, Pietsch T, Bamberg M, Weller M. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010 Nov;11(11):1036-47. Epub 2010 Oct 20. link to original article contains verified protocol PubMed
- Update: Korfel A, Thiel E, Martus P, Möhle R, Griesinger F, Rauch M, Röth A, Hertenstein B, Fischer T, Hundsberger T, Mergenthaler HG, Junghanß C, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Roth P, Bamberg M, Pietsch T, Weller M. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma. Neurology. 2015 Mar 24;84(12):1242-8. Epub 2015 Feb 25. link to original article PubMed
- RTOG 0227: Glass J, Won M, Schultz CJ, Brat D, Bartlett NL, Suh JH, Werner-Wasik M, Fisher BJ, Liepman MK, Augspurger M, Bokstein F, Bovi JA, Solhjem MC, Mehta MP. Phase I and II study of induction chemotherapy with methotrexate, rituximab, and temozolomide, followed by whole-brain radiotherapy and postirradiation temozolomide for primary CNS lymphoma: NRG Oncology RTOG 0227. J Clin Oncol. 2016 May 10;34(14):1620-5. Epub 2016 Mar 28. link to original article contains verified protocol link to PMC article PubMed
- IELSG32: Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosée PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Rudà R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gørløv JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016 May;3(5):e217-27. Epub 2016 Apr 6. link to original article contains verified protocol PubMed
- Update: Ferreri AJM, Cwynarski K, Pulczynski E, Fox CP, Schorb E, La Rosée P, Binder M, Fabbri A, Torri V, Minacapelli E, Falautano M, Ilariucci F, Ambrosetti A, Roth A, Hemmaway C, Johnson P, Linton KM, Pukrop T, Sønderskov Gørløv J, Balzarotti M, Hess G, Keller U, Stilgenbauer S, Panse J, Tucci A, Orsucci L, Pisani F, Levis A, Krause SW, Schmoll HJ, Hertenstein B, Rummel M, Smith J, Pfreundschuh M, Cabras G, Angrilli F, Ponzoni M, Deckert M, Politi LS, Finke J, Reni M, Cavalli F, Zucca E, Illerhaus G; International Extranodal Lymphoma Study Group. Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial. Lancet Haematol. 2017 Nov;4(11):e510-e523. Epub 2017 Oct 17. link to original article PubMed
Relapsed or refractory, salvage therapy
HiDAC
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HiDAC: High Dose Ara-C (Cytarabine)
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Thiel et al. 2010 (G-PCNSL-SG-1) | 2000-2009 | Non-randomized portion of RCT |
Preceding treatment
- Before 2006: Non-response to High-dose methotrexate
- After 2006: Non-response to Methotrexate & Ifosfamide
Chemotherapy
- Cytarabine (Ara-C) 3000 mg/m2 IV over 3 hours every 12 hours on days 1 & 2
21-day cycle for 4 cycles
References
- G-PCNSL-SG-1: Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, Röth A, Hertenstein B, von Toll T, Hundsberger T, Mergenthaler HG, Leithäuser M, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Plasswilm L, Nägele T, Pietsch T, Bamberg M, Weller M. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010 Nov;11(11):1036-47. Epub 2010 Oct 20. link to original article contains verified protocol PubMed
- Update: Korfel A, Thiel E, Martus P, Möhle R, Griesinger F, Rauch M, Röth A, Hertenstein B, Fischer T, Hundsberger T, Mergenthaler HG, Junghanß C, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Roth P, Bamberg M, Pietsch T, Weller M. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma. Neurology. 2015 Mar 24;84(12):1242-8. Epub 2015 Feb 25. link to original article PubMed
CYVE
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CYVE: CYtarabine, VEpesid (Etoposide)
Regimen variant #1
Study | Evidence |
---|---|
Soussain et al. 2001 | Pilot, >20 pts |
Soussain et al. 2008 | Phase II |
Chemotherapy
- Cytarabine (Ara-C) as follows:
- 2000 mg/m2 IV over 3 hours once per day on days 2 to 5
- 50 mg/m2 IV over 12 hours once per day on days 1 to 5
- Etoposide (Vepesid) 200 mg/m2 IV over 2 hours once per day on days 2 to 5
2 cycles
Subsequent treatment
Regimen variant #2
Study | Evidence |
---|---|
Colombat et al. 2006 | Phase II |
Preceding treatment
- Non-response to MVBP x 2
Chemotherapy
- Cytarabine (Ara-C) 1000 mg/m2 IV every 12 hours on days 1 & 2
- Etoposide (Vepesid) 150 mg/m2 IV once per day on days 1 & 2
2 cycles (length not specified)
Subsequent treatment
References
- Soussain C, Suzan F, Hoang-Xuan K, Cassoux N, Levy V, Azar N, Belanger C, Achour E, Ribrag V, Gerber S, Delattre JY, Leblond V. Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol. 2001 Feb 1;19(3):742-9. link to original article contains verified protocol PubMed
- Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broët S, Linassier C, Lamy T; GOELAMS. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. link to original article contains verified protocol PubMed
- Soussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F, Casasnovas O, Dupriez B, Souleau B, Taksin AL, Gisselbrecht C, Jaccard A, Omuro A, Sanson M, Janvier M, Kolb B, Zini JM, Leblond V; Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. J Clin Oncol. 2008 May 20;26(15):2512-8. Epub 2008 Apr 14. link to original article contains verified protocol PubMed
Ifosfamide & Methotrexate
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Regimen
Study | Evidence |
---|---|
Fischer et al. 2008 | Retrospective |
Chemotherapy
- Ifosfamide (Ifex) 1500 to 2000 mg/m2 IV over 3 hours once per day on days 3 to 5
- Methotrexate (MTX) 4000 mg/m2 IV over 4 hours once on day 1
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 CrCl less than 100 mL/min/1.73m2 according to the following formula:
- Dose of methotrexate = (CrCl/100) x 4000 mg/m2; the paper did not specify what method was used for calculating CrCl. Patients with CrCl less than 50 mL/min/1.73m2 were excluded from the study.
Up to 8 cycles (reference did not list timing/criteria to be used for next cycle of therapy)
References
- Retrospective: 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
Whole brain irradiation
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Regimen variant #1
Study | Years of enrollment | Evidence |
---|---|---|
Thiel et al. 2010 (G-PCNSL-SG-1) | 2000-2009 | Non-randomized portion of RCT |
Preceding treatment
- Before 2006: Non-response to high-dose MTX x 6
- After 2006: Non-response to High-dose methotrexate & ifosfamide x 6
Radiotherapy
- Whole-brain irradiation to 45 Gy in 1.5-Gy fractions
Regimen variant #2
Study | Evidence |
---|---|
Colombat et al. 2006 | Phase II |
Preceding treatment
Radiotherapy
- Whole-brain irradiation to 30 Gy in 1.8-Gy fractions plus 10 Gy boost to the tumor bed
Regimen variant #3
Study | Evidence |
---|---|
Nguyen et al. 2005 | Phase II |
The authors do not clearly describe a pre-determined dosing protocol but report that the most common fraction size was 1.5 Gy.
Radiotherapy
- Median dose:
- Patients not receiving a boost: 36 Gy (range 28 to 45 Gy)
- Patients receiving a boost: 36 Gy (range 19.6 to 40 Gy) + 10 Gy (range 10 to 21.6 Gy)
References
- Nguyen PL, Chakravarti A, Finkelstein DM, Hochberg FH, Batchelor TT, Loeffler JS. Results of whole-brain radiation as salvage of methotrexate failure for immunocompetent patients with primary CNS lymphoma. J Clin Oncol. 2005 Mar 1;23(7):1507-13. link to original article contains verified protocol PubMed
- Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broët S, Linassier C, Lamy T; GOELAMS. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. link to original article contains verified protocol PubMed
- G-PCNSL-SG-1: Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, Röth A, Hertenstein B, von Toll T, Hundsberger T, Mergenthaler HG, Leithäuser M, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Plasswilm L, Nägele T, Pietsch T, Bamberg M, Weller M. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010 Nov;11(11):1036-47. Epub 2010 Oct 20. link to original article contains verified protocol PubMed
- Update: Korfel A, Thiel E, Martus P, Möhle R, Griesinger F, Rauch M, Röth A, Hertenstein B, Fischer T, Hundsberger T, Mergenthaler HG, Junghanß C, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Roth P, Bamberg M, Pietsch T, Weller M. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma. Neurology. 2015 Mar 24;84(12):1242-8. Epub 2015 Feb 25. link to original article PubMed
Consolidation after salvage therapy
Bu/TT/Cy, then auto HSCT
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Bu/TT/Cy: Busulfan, ThioTepa, Cyclophosphamide
Regimen
Study | Evidence |
---|---|
Soussain et al. 2001 | Pilot, >20 pts |
Soussain et al. 2008 | Phase II |
Preceding treatment
- CYVE salvage x 2
Chemotherapy
- Busulfan (Myleran) as follows:
- Up to 60 years old: 10 mg/kg PO or 8 mg/kg IV once per day on days -6, -5, and -4
- ≥60 years old: 6 mg/kg PO or 4.8 mg/kg IV once per day on days -6, -5, and -4
- Thiotepa (Thioplex) 250 mg/m2 IV once per day on days -9, -8, and -7
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
Supportive medications
- Clonazepam (Klonopin) 2 mg/day IV from the first day of Busulfan (Myleran) until completion of Busulfan (Myleran)
Stem cell re-infusion occurs on day 0
References
- Soussain C, Suzan F, Hoang-Xuan K, Cassoux N, Levy V, Azar N, Belanger C, Achour E, Ribrag V, Gerber S, Delattre JY, Leblond V. Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol. 2001 Feb 1;19(3):742-9. link to original article contains verified protocol PubMed
- Soussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F, Casasnovas O, Dupriez B, Souleau B, Taksin AL, Gisselbrecht C, Jaccard A, Omuro A, Sanson M, Janvier M, Kolb B, Zini JM, Leblond V; Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. J Clin Oncol. 2008 May 20;26(15):2512-8. Epub 2008 Apr 14. link to original article contains verified protocol PubMed
Relapsed or refractory, subsequent lines of therapy
Rituximab monotherapy
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Regimen
Study | Evidence |
---|---|
Batchelor et al. 2011 | Pilot, <20 pts |
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days 1, 8, 15, 22
28-day cycle for up to 2 cycles
References
- Batchelor TT, Grossman SA, Mikkelsen T, Ye for, Desideri S, Lesser GJ. Rituximab monotherapy for patients with recurrent primary CNS lymphoma. Neurology. 2011 Mar 8;76(10):929-30. link to original article contains verified protocol link to PMC article PubMed
Temozolomide monotherapy
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Regimen
Study | Evidence |
---|---|
Reni et al. 2007 | Phase II |
Chemotherapy
- Temozolomide (Temodar) 150 mg/m2 PO once per day on days 1 to 5
28-day cycles
References
- Reni M, Zaja F, Mason W, Perry J, Mazza E, Spina M, Bordonaro R, Ilariucci F, Faedi M, Corazzelli G, Manno P, Franceschi E, Pace A, Candela M, Abbadessa A, Stelitano C, Latte G, Ferreri AJ. Temozolomide as salvage treatment in primary brain lymphomas. Br J Cancer. 2007 Mar 26;96(6):864-7. Epub 2007 Feb 27. link to original article contains verified protocol link to PMC article PubMed
Temsirolimus monotherapy
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Regimen
Study | Evidence |
---|---|
Korfel et al. 2016 (TemPCNSL) | Phase II |
This is the dose used in stage 2 of this two-stage protocol.
Targeted therapy
- Temsirolimus (Torisel) 75 mg IV once per day on days 1, 8, 15, 22
28-day cycles
References
- TemPCNSL: Korfel A, Schlegel U, Herrlinger U, Dreyling M, Schmidt C, von Baumgarten L, Pezzutto A, Grobosch T, Kebir S, Thiel E, Martus P, Kiewe P. Phase II trial of temsirolimus for relapsed/refractory primary CNS lymphoma. J Clin Oncol. 2016 May 20;34(15):1757-63. Epub 2016 Mar 14. link to original article contains verified protocol PubMed
Topotecan monotherapy
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Regimen
Study | Evidence |
---|---|
Fischer et al. 2006 | Phase II |
Voloschin et al. 2008 | Phase II, <20 pts |
Chemotherapy
- Topotecan (Hycamtin) 1.5 mg/m2 IV over 30 minutes once per day on days 1 to 5
Supportive medications
- Voloschin et al. 2008: Ondansetron (Zofran) (dose/route not specified) prior to Topotecan (Hycamtin)
21-day cycle for 6 to 10 cycles
References
- Fischer L, Thiel E, Klasen HA, Birkmann J, Jahnke K, Martus P, Korfel A. Prospective trial on topotecan salvage therapy in primary CNS lymphoma. Ann Oncol. 2006 Jul;17(7):1141-5. Epub 2006 Apr 7. link to original article contains verified protocol PubMed
- Voloschin AD, Betensky R, Wen PY, Hochberg F, Batchelor T. Topotecan as salvage therapy for relapsed or refractory primary central nervous system lymphoma. J Neurooncol. 2008 Jan;86(2):211-5. Epub 2007 Sep 21. link to original article contains verified protocol PubMed
Prognosis
IELSG Prognostic Scoring System (2003)
- Ferreri AJ, Blay JY, Reni M, Pasini F, Spina M, Ambrosetti A, Calderoni A, Rossi A, Vavassori V, Conconi A, Devizzi L, Berger F, Ponzoni M, Borisch B, Tinguely M, Cerati M, Milani M, Orvieto E, Sanchez J, Chevreau C, Dell'Oro S, Zucca E, Cavalli F. Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J Clin Oncol. 2003 Jan 15;21(2):266-72. to original article PubMed