Difference between revisions of "CNS lymphoma"
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− | + | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | |
− | + | [[#top|Back to Top]] | |
− | + | </div> | |
− | + | {{#lst:Editorial board transclusions|cnsl}} | |
− | + | ''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[CNS lymphoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it!'' | |
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{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
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=Guidelines= | =Guidelines= | ||
+ | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' | ||
==BSH== | ==BSH== | ||
− | *'''2018:''' Fox et al. [https:// | + | *'''2018:''' Fox et al. [https://doi.org/10.1111/bjh.15661 Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma] [https://pubmed.ncbi.nlm.nih.gov/30467845 PubMed] |
==EANO== | ==EANO== | ||
− | *'''2015:''' Hoang-Xuan et al. [ | + | *'''2015:''' Hoang-Xuan et al. [https://doi.org/10.1016/s1470-2045(15)00076-5 Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology] [https://pubmed.ncbi.nlm.nih.gov/26149884 PubMed] |
+ | ==EHA/ESMO== | ||
+ | *'''2024:''' Ferreri et al. [https://doi.org/10.1016/j.annonc.2023.11.010 Primary central nervous system lymphomas: EHA-ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/38839484/ PubMed] | ||
==ESH== | ==ESH== | ||
− | *'''2019:''' Fox et al. [https:// | + | *'''2019:''' Fox et al. [https://doi.org/10.1111/bjh.15661 Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma] [https://pubmed.ncbi.nlm.nih.gov/30467845 PubMed] |
− | |||
− | |||
+ | ==[https://www.esmo.org/ ESMO]== | ||
+ | *'''2016:''' Vitolo et al. [https://doi.org/10.1093/annonc/mdw175 Extranodal diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/27377716/ PubMed] | ||
==GEL/TAMO== | ==GEL/TAMO== | ||
− | *'''2016:''' Peñalver et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286932/ Guidelines for diagnosis, prevention and management of central nervous system involvement in diffuse large B-cell lymphoma patients by the Spanish Lymphoma Group (GELTAMO)] | + | *'''2016:''' Peñalver et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286932/ Guidelines for diagnosis, prevention and management of central nervous system involvement in diffuse large B-cell lymphoma patients by the Spanish Lymphoma Group (GELTAMO)] [https://pubmed.ncbi.nlm.nih.gov/27846613 PubMed] |
− | == | + | ==NCCN== |
− | *[https://www.nccn.org/ | + | *''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425 NCCN Guidelines - Central Nervous System Cancers].'' |
=CNS prophylaxis, systemic therapy= | =CNS prophylaxis, systemic therapy= | ||
− | ==HiDAC {{#subobject:75c24e|Regimen=1}}== | + | ==High-dose Cytarabine monotherapy (HiDAC) {{#subobject:75c24e|Regimen=1}}== |
− | |||
− | |||
− | |||
− | |||
HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:0258f4|Variant=1}}=== | ===Regimen {{#subobject:0258f4|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://doi.org/10.1093/annonc/mds621 Holte et al. 2013 ( | + | |[https://doi.org/10.1093/annonc/mds621 Holte et al. 2013 (NLG LBC-04)] |
− | |style="background-color:#91cf61"|Phase | + | |2004-2008 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
''Note: IT treatment was not part of prophylaxis, except that [[Methotrexate (MTX)]] 15 mg IT was allowed at time of diagnostic LP.'' | ''Note: IT treatment was not part of prophylaxis, except that [[Methotrexate (MTX)]] 15 mg IT was allowed at time of diagnostic LP.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Diffuse_large_B-cell_lymphoma#R-CHOEP-14|R-CHOEP-14]] x 8 | + | *Induction [[Diffuse_large_B-cell_lymphoma#R-CHOEP-14|R-CHOEP-14]] x 8 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV twice per day on days 1 & 2 (total dose: 12,000 mg/m<sup>2</sup>) | + | *[[Cytarabine (Ara-C)]] by the following age-based criteria: |
− | ** | + | **Younger than 60 years old: 3000 mg/m<sup>2</sup> IV twice per day on days 1 & 2 (total dose: 12,000 mg/m<sup>2</sup>) |
− | + | **60 to 65 years old: 2000 mg/m<sup>2</sup> IV twice per day on days 1 & 2 (total dose: 8000 mg/m<sup>2</sup>) | |
+ | **Older than 65 years old: not defined | ||
'''21-day course''' | '''21-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Methotrexate_monotherapy|HD-MTX]] | + | *Induction [[#Methotrexate_monotherapy|HD-MTX]] |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # ''' | + | # '''NLG LBC-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. [https://doi.org/10.1093/annonc/mds621 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23247661/ PubMed] [https://clinicaltrials.gov/study/NCT01502982 NCT01502982] |
− | |||
==Methotrexate monotherapy {{#subobject:e89965|Regimen=1}}== | ==Methotrexate monotherapy {{#subobject:e89965|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:a5d109|Variant=1}}=== | ===Regimen {{#subobject:a5d109|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://doi.org/10.1093/annonc/mds621 Holte et al. 2013 ( | + | |[https://doi.org/10.1093/annonc/mds621 Holte et al. 2013 (NLG LBC-04)] |
− | |style="background-color:#91cf61"|Phase | + | |2004-2008 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
''Note: IT treatment was not part of prophylaxis, except that [[Methotrexate (MTX)]] 15 mg IT was allowed at time of diagnostic LP.'' | ''Note: IT treatment was not part of prophylaxis, except that [[Methotrexate (MTX)]] 15 mg IT was allowed at time of diagnostic LP.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *Induction [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 | *[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Leucovorin (Folinic acid)]] (dose/frequency not specified) starting at 36 hours |
− | *[[Folinic acid | ||
− | |||
'''One course''' | '''One course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # ''' | + | # '''NLG LBC-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. [https://doi.org/10.1093/annonc/mds621 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23247661/ PubMed] [https://clinicaltrials.gov/study/NCT01502982 NCT01502982] |
=CNS treatment, local therapy= | =CNS treatment, local therapy= | ||
==IT Cytarabine monotherapy {{#subobject:867516|Regimen=1}}== | ==IT Cytarabine monotherapy {{#subobject:867516|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:a436da|Variant=1}}=== | ===Regimen {{#subobject:a436da|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.1999.17.10.3110 Glantz et al. 1999] | |[https://doi.org/10.1200/jco.1999.17.10.3110 Glantz et al. 1999] | ||
− | |style="background-color:#1a9851"|Phase | + | |1994-1998 |
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
|[[#IT_Cytarabine_liposomal_monotherapy|IT liposomal cytarabine]] | |[[#IT_Cytarabine_liposomal_monotherapy|IT liposomal cytarabine]] | ||
|style="background-color:#d73027"|Inferior ORR | |style="background-color:#d73027"|Inferior ORR | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====CNS therapy, treatment==== | ||
*[[Cytarabine (Ara-C)]] 50 mg IT once per day on days 1, 4, 8, 11, 15, 18, 22, 25 | *[[Cytarabine (Ara-C)]] 50 mg IT once per day on days 1, 4, 8, 11, 15, 18, 22, 25 | ||
− | |||
'''4-week course''' | '''4-week course''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *Further therapy was given to responders; see text for details | + | *Glantz et al. 1999, responders: Further therapy was given to responders; see text for details |
− | + | </div></div> | |
===References=== | ===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. [https://doi.org/10.1200/jco.1999.17.10.3110 link to original article] ''' | + | # 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. [https://doi.org/10.1200/jco.1999.17.10.3110 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10506606/ PubMed] |
− | |||
==IT Cytarabine liposomal monotherapy {{#subobject:fbf1d4|Regimen=1}}== | ==IT Cytarabine liposomal monotherapy {{#subobject:fbf1d4|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:c43afb|Variant=1}}=== | ===Regimen {{#subobject:c43afb|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.1999.17.10.3110 Glantz et al. 1999] | |[https://doi.org/10.1200/jco.1999.17.10.3110 Glantz et al. 1999] | ||
− | |style="background-color:#1a9851"|Phase | + | |1994-1998 |
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic) | ||
|[[#IT_Cytarabine_monotherapy_2|IT cytarabine]] | |[[#IT_Cytarabine_monotherapy_2|IT cytarabine]] | ||
− | |style="background-color:#1a9850"|Superior ORR | + | |style="background-color:#1a9850"|Superior ORR (secondary endpoint) |
|- | |- | ||
|} | |} | ||
− | ==== | + | ''Note: this study was not designed to make formal statitiscal comparisons, but the difference in ORR was very large.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====CNS therapy, treatment==== | ||
*[[Cytarabine liposomal (DepoCyt)]] 50 mg IT once on day 1 | *[[Cytarabine liposomal (DepoCyt)]] 50 mg IT once on day 1 | ||
− | |||
'''14-day cycle for 2 cycles''' | '''14-day cycle for 2 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *Further therapy was given to responders; see text for details | + | *Glantz et al. 1999, responders: Further therapy was given to responders; see text for details |
− | + | </div></div> | |
===References=== | ===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. [https://doi.org/10.1200/jco.1999.17.10.3110 link to original article] ''' | + | # 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. [https://doi.org/10.1200/jco.1999.17.10.3110 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10506606/ PubMed] |
− | |||
=Upfront therapy, randomized data= | =Upfront therapy, randomized data= | ||
− | + | ==Cytarabine & Methotrexate (CYM) {{#subobject:eef91c|Regimen=1}}== | |
− | ==CYM {{#subobject:eef91c|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CYM: '''<u>CY</u>'''tarabine & '''<u>M</u>'''ethotrexate | CYM: '''<u>CY</u>'''tarabine & '''<u>M</u>'''ethotrexate | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:5ead03|Variant=1}}=== | ===Regimen {{#subobject:5ead03|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(09)61416-1 Ferreri et al. 2009 (IELSG20)] |
− | |style="background-color:#1a9851"|Randomized Phase | + | |2004-2007 |
+ | |style="background-color:#1a9851"|Randomized Phase 2, >20 per arm (E-esc) | ||
|[[#Methotrexate_monotherapy_2|High-dose MTX]] | |[[#Methotrexate_monotherapy_2|High-dose MTX]] | ||
− | |style="background-color:#91cf60"|Seems to have superior CR rate | + | |style="background-color:#91cf60"|Seems to have superior CR rate (primary endpoint) |
|- | |- | ||
− | |rowspan=2|[https:// | + | |rowspan=2|[https://doi.org/10.1016/S2352-3026(16)00036-3 Ferreri et al. 2016 (IELSG32)] |
− | |rowspan=2 style="background-color:#1a9851"|Randomized Phase | + | |rowspan=2|2010-2014 |
+ | |rowspan=2 style="background-color:#1a9851"|Randomized Phase 2 (C) | ||
|1. [[#Cytarabine.2C_Methotrexate.2C_Rituximab|Cytarabine, Methotrexate, Rituximab]] | |1. [[#Cytarabine.2C_Methotrexate.2C_Rituximab|Cytarabine, Methotrexate, Rituximab]] | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate | |style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate | ||
Line 177: | Line 180: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====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>) | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*As described in Ferreri et al. 2016: | *As described in Ferreri et al. 2016: | ||
− | *[[Levoleucovorin (Fusilev)]] 15 mg/m<sup>2</sup> IV every 6 hours for 12 doses, beginning 24 hours after the '''start''' of | + | *[[Levoleucovorin (Fusilev)]] 15 mg/m<sup>2</sup> IV every 6 hours for 12 doses, beginning 24 hours after the '''start''' of methotrexate, with modifications if MTX level is high 48 hours after the '''end''' of the infusion; see paper for details |
− | |||
− | |||
'''21-day cycle for 4 cycles''' | '''21-day cycle for 4 cycles''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *IELSG20: [[#Whole_brain_irradiation|Whole brain irradiation]], within 4 weeks | + | *IELSG20: [[#Whole_brain_irradiation|Whole brain irradiation]] consolidation , within 4 weeks |
− | *IELSG32: [[#Whole_brain_irradiation|Whole brain irradiation]] versus [[#BCNU.2FTT.2C_then_auto_HSCT|Carmustine & Thiotepa with auto HSCT]] | + | *IELSG32: [[#Whole_brain_irradiation|Whole brain irradiation]] versus [[#BCNU.2FTT.2C_then_auto_HSCT|Carmustine & Thiotepa with auto HSCT]] consolidation |
− | + | </div></div> | |
===References=== | ===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. [https:// | + | # '''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. [https://doi.org/10.1016/S0140-6736(09)61416-1 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19767089/ PubMed] [https://clinicaltrials.gov/study/NCT00210314 NCT00210314] |
− | # '''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. [https:// | + | # '''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. [https://doi.org/10.1016/S2352-3026(16)00036-3 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27132696/ PubMed] [https://clinicaltrials.gov/study/NCT01011920 NCT01011920] |
− | |||
==Cytarabine, Methotrexate, Rituximab {{#subobject:a4671e|Regimen=1}}== | ==Cytarabine, Methotrexate, Rituximab {{#subobject:a4671e|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
R-HD-MTX/ARA-C: '''<u>R</u>'''ituximab, '''<u>H</u>'''igh-'''<u>D</u>'''ose '''<u>M</u>'''etho'''<u>T</u>'''re'''<u>X</u>'''ate, '''<u>ARA-C</u>''' (Cytarabine) | R-HD-MTX/ARA-C: '''<u>R</u>'''ituximab, '''<u>H</u>'''igh-'''<u>D</u>'''ose '''<u>M</u>'''etho'''<u>T</u>'''re'''<u>X</u>'''ate, '''<u>ARA-C</u>''' (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:1c6830|Variant=1}}=== | ===Regimen {{#subobject:1c6830|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2015.61.1236 Ferreri et al. 2015 (SCNSL1)] |
− | |style="background-color:#91cf61"|Phase | + | |2006-2013 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |rowspan=2|[https:// | + | |rowspan=2|[https://doi.org/10.1016/S2352-3026(16)00036-3 Ferreri et al. 2016 (IELSG32)] |
− | |rowspan=2 style="background-color:#1a9851"|Randomized Phase | + | |rowspan=2|2010-2014 |
− | |1. [[#CYM | + | |rowspan=2 style="background-color:#1a9851"|Randomized Phase 2 (E-esc) |
+ | |1. [[#Cytarabine_.26_Methotrexate_.28CYM.29|CYM]] | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate | |style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate | ||
|- | |- | ||
Line 224: | Line 225: | ||
|} | |} | ||
''Note: SCNSL1 was intended for secondary CNS lymphoma, whereas IELSG32 was intended for primary CNS lymphoma.'' | ''Note: SCNSL1 was intended for secondary CNS lymphoma, whereas IELSG32 was intended for primary CNS lymphoma.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *SCNSL1: R-CHOP x 1 | + | *SCNSL1: Induction [[Diffuse_large_B-cell_lymphoma#R-CHOP|R-CHOP]] x 1 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====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>) |
− | *[[Rituximab (Rituxan)]] 375 | + | ====Targeted therapy==== |
− | + | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -5 & 0 | |
====CNS therapy==== | ====CNS therapy==== | ||
*SCNSL1: [[Cytarabine liposomal (DepoCyt)]] | *SCNSL1: [[Cytarabine liposomal (DepoCyt)]] | ||
− | ====Supportive | + | ====Supportive therapy==== |
− | *[[Levoleucovorin (Fusilev)]] 15 mg/m<sup>2</sup> IV every 6 hours for 12 doses, beginning 24 hours after the '''start''' of | + | *[[Levoleucovorin (Fusilev)]] 15 mg/m<sup>2</sup> IV every 6 hours for 12 doses, beginning 24 hours after the '''start''' of methotrexate, with modifications if MTX level is high 48 hours after the '''end''' of the infusion; see paper for details |
− | |||
− | |||
'''21-day cycle for 4 cycles''' | '''21-day cycle for 4 cycles''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
*SCNSL1: Intensification phase (see paper for details) | *SCNSL1: Intensification phase (see paper for details) | ||
− | * | + | *IELSG32: [[#Whole_brain_irradiation|Whole brain irradiation]] versus [[#BCNU.2FTT.2C_then_auto_HSCT|Carmustine & Thiotepa with auto HSCT]] consolidation |
− | + | </div></div> | |
===References=== | ===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. [ | + | # '''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. [https://doi.org/10.1200/jco.2015.61.1236 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26282634/ PubMed] [https://clinicaltrials.gov/study/NCT00801216 NCT00801216] |
− | # '''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. [https:// | + | # '''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. [https://doi.org/10.1016/S2352-3026(16)00036-3 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27132696/ PubMed] [https://clinicaltrials.gov/study/NCT01011920 NCT01011920] |
− | |||
==MATRix {{#subobject:7b7130|Regimen=1}}== | ==MATRix {{#subobject:7b7130|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
MATRix: '''<u>M</u>'''ethotrexate, '''<u>A</u>'''ra-C (Cytarabine), '''<u>T</u>'''hiotepa, '''<u>Ri</u>'''tu'''<u>x</u>'''imab | MATRix: '''<u>M</u>'''ethotrexate, '''<u>A</u>'''ra-C (Cytarabine), '''<u>T</u>'''hiotepa, '''<u>Ri</u>'''tu'''<u>x</u>'''imab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:278704|Variant=1}}=== | ===Regimen {{#subobject:278704|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[https:// | + | |rowspan=2|[https://doi.org/10.1016/S2352-3026(16)00036-3 Ferreri et al. 2016 (IELSG32)] |
− | |rowspan=2 style="background-color:#1a9851"|Randomized Phase | + | |rowspan=2|2010-2014 |
− | |1. [[#CYM | + | |rowspan=2 style="background-color:#1a9851"|Randomized Phase 2 (E-esc) |
− | |style="background-color:#1a9850"|Superior CR rate | + | |1. [[#Cytarabine_.26_Methotrexate_.28CYM.29|CYM]] |
+ | |style="background-color:#1a9850"|Superior CR rate (primary endpoint) | ||
|- | |- | ||
|2. [[#Cytarabine.2C_Methotrexate.2C_Rituximab|Cytarabine, Methotrexate, Rituximab]] | |2. [[#Cytarabine.2C_Methotrexate.2C_Rituximab|Cytarabine, Methotrexate, Rituximab]] | ||
− | |style="background-color:#91cf60"|Seems to have superior CR rate | + | |style="background-color:#91cf60"|Seems to have superior CR rate (primary endpoint) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[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>) | ||
*[[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 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Levoleucovorin (Fusilev)]] 15 mg/m<sup>2</sup> IV every 6 hours for 12 doses, beginning 24 hours after the '''start''' of methotrexate, with modifications if MTX level is high 48 hours after the '''end''' of the infusion; see paper for details |
− | *[[Levoleucovorin (Fusilev)]] 15 mg/m<sup>2</sup> IV every 6 hours for 12 doses, beginning 24 hours after the '''start''' of | ||
− | |||
− | |||
'''21-day cycle for 4 cycles''' | '''21-day cycle for 4 cycles''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Whole_brain_irradiation|Whole brain irradiation]] versus [[#BCNU.2FTT.2C_then_auto_HSCT|Carmustine & Thiotepa with auto HSCT]] | + | *[[#Whole_brain_irradiation|Whole brain irradiation]] versus [[#BCNU.2FTT.2C_then_auto_HSCT|Carmustine & Thiotepa with auto HSCT]] consolidation |
− | + | </div></div> | |
===References=== | ===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. [https:// | + | # '''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. [https://doi.org/10.1016/S2352-3026(16)00036-3 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27132696/ PubMed] [https://clinicaltrials.gov/study/NCT01011920 NCT01011920] |
− | |||
==MBVP {{#subobject:7b8320|Regimen=1}}== | ==MBVP {{#subobject:7b8320|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
MBVP: '''<u>M</u>'''ethotrexate, '''<u>B</u>'''CNU (Carmustine), '''<u>V</u>'''umon (Teniposide), '''<u>P</u>'''rednisone | MBVP: '''<u>M</u>'''ethotrexate, '''<u>B</u>'''CNU (Carmustine), '''<u>V</u>'''umon (Teniposide), '''<u>P</u>'''rednisone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:27aa04|Variant=1}}=== | ===Regimen {{#subobject:27aa04|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(18)30747-2 Bromberg et al. 2019 (HOVON 105/ALLG NHL 24)] |
− | |style="background-color:#1a9851"|Phase | + | |2010-2016 |
− | |R-MBVP | + | |style="background-color:#1a9851"|Phase 3 (C) |
+ | |[[#R-MBVP_999|R-MBVP]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of EFS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 15 | *[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 15 | ||
*[[Carmustine (BCNU)]] 100 mg/m<sup>2</sup> IV once on day 4 | *[[Carmustine (BCNU)]] 100 mg/m<sup>2</sup> IV once on day 4 | ||
*[[Teniposide (Vumon)]] 100 mg/m<sup>2</sup> IV once per day on days 2 & 3 | *[[Teniposide (Vumon)]] 100 mg/m<sup>2</sup> IV once per day on days 2 & 3 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 5 | *[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
− | |||
'''28-day cycle for 2 cycles''' | '''28-day cycle for 2 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *HOVON 105/ALLG NHL 24, responders 60 years old or older: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29_2|HiDAC]] consolidation |
− | * | + | *HOVON 105/ALLG NHL 24, responders younger than 60: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29_2|HiDAC]] consolidation, then [[#Whole_brain_irradiation|low-dose WBRT]] consolidation |
+ | </div></div> | ||
===References=== | ===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. [https:// | + | # '''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. [https://doi.org/10.1016/S1470-2045(18)30747-2 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30630772/ PubMed] ACTRN12610000908033 |
− | + | ## '''HRQoL analysis:''' van der Meulen M, Bakunina K, Nijland M, Minnema MC, Cull G, Stevens WBC, Baars JW, Mason KD, Beeker A, Beijert M, Taphoorn MJB, van den Bent MJ, Issa S, Doorduijn JK, Bromberg JEC, Dirven L. Health-related quality of life after chemotherapy with or without rituximab in primary central nervous system lymphoma patients: results from a randomised phase III study. Ann Oncol. 2020 Aug;31(8):1046-1055. Epub 2020 May 3. [https://doi.org/10.1016/j.annonc.2020.04.014 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32371123/ PubMed] | |
==Methotrexate monotherapy {{#subobject:031ce9|Regimen=1}}== | ==Methotrexate monotherapy {{#subobject:031ce9|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, 3500 mg/m<sup>2</sup> {{#subobject:8ce96f|Variant=1}}=== | ===Regimen variant #1, 3500 mg/m<sup>2</sup> {{#subobject:8ce96f|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(09)61416-1 Ferreri et al. 2009 (IELSG20)] |
− | |style="background-color:#1a9851"|Randomized Phase | + | |2004-2007 |
− | |[[#CYM | + | |style="background-color:#1a9851"|Randomized Phase 2 (C) |
+ | |[[#Cytarabine_.26_Methotrexate_.28CYM.29|CYM]]; high-dose | ||
|style="background-color:#fc8d59"|Seems to have inferior CR rate | |style="background-color:#fc8d59"|Seems to have inferior CR rate | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[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>) | ||
− | |||
'''21-day cycle for 4 cycles''' | '''21-day cycle for 4 cycles''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Whole_brain_irradiation|Whole brain irradiation]], within 4 weeks | + | *[[#Whole_brain_irradiation|Whole brain irradiation]] consolidation, within 4 weeks |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 4000 mg/m<sup>2</sup> {{#subobject:dcc365|Variant=1}}=== | ===Regimen variant #2, 4000 mg/m<sup>2</sup> {{#subobject:dcc365|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable" style="width: 60%; text-align:center;" |
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(10)70229-1 Thiel et al. 2010 (G-PCNSL-SG-1)] |
|2000-2009 | |2000-2009 | ||
− | |style="background-color:#91cf61"|Non-randomized | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT |
|- | |- | ||
|} | |} | ||
− | + | ''Note: All patients received the same induction regimen; however, the induction regimen was changed after 2006 to [[#Ifosfamide_.26_Methotrexate|high-dose MTX & ifosfamide]].'' | |
− | ''All patients received the same induction regimen; however, the induction regimen was changed after 2006 to [[#Ifosfamide_.26_Methotrexate|high-dose MTX & ifosfamide]].'' | + | <div class="toccolours" style="background-color:#b3e2cd"> |
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 4000 mg/m<sup>2</sup> IV over 4 hours once on day 1 | *[[Methotrexate (MTX)]] 4000 mg/m<sup>2</sup> IV over 4 hours once on day 1 | ||
− | |||
'''14-day cycle for 6 cycles''' | '''14-day cycle for 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *G-PCNSL-SG-1, patients with CR: [[#Whole_brain_irradiation|whole-brain irradiation]] consolidation versus [[CNS_lymphoma_-_null_regimens#Observation|no further treatment]] |
− | * | + | *G-PCNSL-SG-1, patients with less than CR in the WB-XRT arm: Salvage [[#Whole_brain_irradiation_2|whole-brain irradiation]] |
− | * | + | *G-PCNSL-SG-1, patients with less than CR in the no-WB-XRT: Salvage [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29_3|HiDAC]] |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 8000 mg/m<sup>2</sup> {{#subobject:8e0230|Variant=1}}=== | ===Regimen variant #3, 8000 mg/m<sup>2</sup> {{#subobject:8e0230|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/ana.20495 Herrlinger et al. 2005 (NOA-03)] |
− | |style="background-color:#91cf61"|Phase | + | |1998-05 to 2000-03 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | + | ''Note: This was considered a negative trial by the authors and is included here for historical purposes.'' | |
− | ''This was considered a negative trial by the authors and is included here for historical purposes.'' | + | <div class="toccolours" style="background-color:#b3e2cd"> |
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once on day 1 | *[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once on day 1 | ||
− | |||
'''14-day cycle for 6 cycles''' | '''14-day cycle for 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *NOA-03, patients intolerant of MTX or not achieving CR after 6 cycles: Salvage [[#Whole_brain_irradiation_2|whole-brain irradiation]] versus [[#PCV_999|PCV]]; see article for details |
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #4, 8000 mg/m<sup>2</sup> with renal adjustment {{#subobject:567824|Variant=1}}=== | ===Regimen variant #4, 8000 mg/m<sup>2</sup> with renal adjustment {{#subobject:567824|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2003.03.036 Batchelor et al. 2003 (NABTT 96-07)] |
− | |style="background-color:#91cf61"|Phase | + | |1998-1999 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once on day 1 | + | *[[Methotrexate (MTX)]] by the following renal function-based criteria: |
− | ** | + | **CrCl 100 mL/min/1.73m<sup>2</sup> or more: 8000 mg/m<sup>2</sup> IV over 4 hours once on day 1 |
− | + | **CrCl less than 100 mL/min/1.73m<sup>2</sup>: The dose was reduced by the percentage reduction below 100. For example, a CrCl of 50 mL/min/1.73m<sup>2</sup> would mandate a 50% dose reduction to 4000 mg/m<sup>2</sup>. | |
'''14-day cycle until CR or a maximum of 8 cycles''' | '''14-day cycle until CR or a maximum of 8 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *NABTT 96-07, patients achieving CR: [[#Methotrexate_monotherapy_2|HD-MTX]] continuation x 2, then [[#Methotrexate_monotherapy_3|methotrexate]] maintenance |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #5, 20-day course {{#subobject:a12fcc|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | + | !style="width: 33%"|Study | |
− | + | !style="width: 33%"|Dates of enrollment | |
− | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | ===Regimen variant # | ||
− | {| class="wikitable" style="width: | ||
− | !style="width: | ||
− | !style="width: | ||
|- | |- | ||
|[https://doi.org/10.1093/annonc/mdl458 Montemurro et al. 2007 (OSHO-53)] | |[https://doi.org/10.1093/annonc/mdl458 Montemurro et al. 2007 (OSHO-53)] | ||
− | |style="background-color:#91cf61"|Phase | + | |1999-2004 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 & 10 | + | *[[Methotrexate (MTX)]] by the following age-based criteria: |
− | + | **60 years old or younger: 8000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 & 10 | |
+ | **Older than 60 years old: 6000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 & 10 | ||
'''20-day course''' | '''20-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *OSHO-53, responders (CR or PR): [[#Bu.2FTT.2C_then_auto_HSCT|Bu/TT, then autologous HSCT]] consolidation |
− | + | </div></div> | |
===References=== | ===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. [ | + | # '''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. [https://doi.org/10.1200/jco.2003.03.036 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12637469/ 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. [https:// | + | # '''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. [https://doi.org/10.1002/ana.20495 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15929034/ PubMed] content property of [https://hemonc.org 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. [https://doi.org/10.1093/annonc/mdl458 link to original article] ''' | + | # '''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. [https://doi.org/10.1093/annonc/mdl458 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17185743/ 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. [https:// | + | # '''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. [https://doi.org/10.1016/S0140-6736(09)61416-1 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19767089/ PubMed] [https://clinicaltrials.gov/study/NCT00210314 NCT00210314] |
− | # '''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. [https:// | + | # '''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. [https://doi.org/10.1016/S1470-2045(10)70229-1 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20970380/ PubMed] [https://clinicaltrials.gov/study/NCT00153530 NCT00153530] |
− | <!-- ## '''Update: Abstract:''' Agnieszka Korfel, Eckhard Thiel, Peter Martus, Robert Moehle, Frank Griesinger, Michael Rauch, Alexander Roeth, Bernd Hertenstein, Thomas Fischer, Thomas Hundsberger, Hans-Guenther Mergenthaler, Christian Junghanss, Tobias Birnbaum, Lars Fischer, Kristoph Jahnke, Ulrich Herrlinger, Ludwig Plasswilm, Thomas Naegele, Torsten Pietsch, Michael Weller. G-PCNSL-SG-1 randomized phase III trial of high-dose methotrexate with or without whole brain radiotherapy for primary central nervous system lymphoma: Long-term follow-up. J Clin Oncol 32:5s, 2014 (suppl; abstr 8527) [ | + | <!-- ## '''Update: Abstract:''' Agnieszka Korfel, Eckhard Thiel, Peter Martus, Robert Moehle, Frank Griesinger, Michael Rauch, Alexander Roeth, Bernd Hertenstein, Thomas Fischer, Thomas Hundsberger, Hans-Guenther Mergenthaler, Christian Junghanss, Tobias Birnbaum, Lars Fischer, Kristoph Jahnke, Ulrich Herrlinger, Ludwig Plasswilm, Thomas Naegele, Torsten Pietsch, Michael Weller. G-PCNSL-SG-1 randomized phase III trial of high-dose methotrexate with or without whole brain radiotherapy for primary central nervous system lymphoma: Long-term follow-up. J Clin Oncol 32:5s, 2014 (suppl; abstr 8527) [https://doi.org/10.1200/jco.2014.32.15_suppl.8527 link to abstract] --> |
− | ## '''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. [ | + | ## '''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. [https://doi.org/10.1212/wnl.0000000000001395 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25716362/ PubMed] |
=Upfront therapy, non-randomized or retrospective data= | =Upfront therapy, non-randomized or retrospective data= | ||
− | |||
==Lomustine, Methotrexate, Procarbazine {{#subobject:95c040|Regimen=1}}== | ==Lomustine, Methotrexate, Procarbazine {{#subobject:95c040|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
MCP: '''<u>M</u>'''ethotrexate, '''<u>C</u>'''CNU (Lomustine), '''<u>P</u>'''rocarbazine | MCP: '''<u>M</u>'''ethotrexate, '''<u>C</u>'''CNU (Lomustine), '''<u>P</u>'''rocarbazine | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:0caeaa|Variant=1}}=== | ===Regimen {{#subobject:0caeaa|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1093/annonc/mdn628 Illerhaus et al. 2008a] | |[https://doi.org/10.1093/annonc/mdn628 Illerhaus et al. 2008a] | ||
− | |style="background-color:#91cf61"|Phase | + | |1998-2004 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 1 | *[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 1 | ||
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1, 15, 30 | *[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1, 15, 30 | ||
*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 10 | *[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 10 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> (route not specified) every 6 hours beginning 24 hours after start of methotrexate infusion, continued until clearance |
− | *[[Folinic acid | ||
− | |||
'''45-day cycle for up to 3 cycles''' | '''45-day cycle for up to 3 cycles''' | ||
− | + | </div></div> | |
===References=== | ===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. [https://doi.org/10.1093/annonc/mdn628 link to original article] ''' | + | # 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. [https://doi.org/10.1093/annonc/mdn628 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18953065/ PubMed] |
− | |||
==Lomustine, Methotrexate, Procarbazine, Methylprednisolone {{#subobject:c81fd|Regimen=1}}== | ==Lomustine, Methotrexate, Procarbazine, Methylprednisolone {{#subobject:c81fd|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
===Regimen {{#subobject:d3269c|Variant=1}}=== | ===Regimen {{#subobject:d3269c|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2003.11.036 Hoang-Xuan et al. 2003 (EORTC 26952)] |
− | |style="background-color:#91cf61"|Phase | + | |1997-1999 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''This was the first prospective phase | + | ''Note: This was the first prospective phase 2 trial evaluating chemotherapy alone in older patients with PCNSL.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 10, 20 | *[[Methotrexate (MTX)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 10, 20 | ||
*[[Lomustine (CCNU)]] 40 mg/m<sup>2</sup> PO once on day 1 | *[[Lomustine (CCNU)]] 40 mg/m<sup>2</sup> PO once on day 1 | ||
*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 7 | *[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 7 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Methylprednisolone (Solumedrol)]] as follows: | *[[Methylprednisolone (Solumedrol)]] as follows: | ||
**Days 1 to 20: 120 mg/m<sup>2</sup> IV or PO every other day | **Days 1 to 20: 120 mg/m<sup>2</sup> IV or PO every other day | ||
**Days 20 to 45: 60 mg/m<sup>2</sup> IV or PO every other day | **Days 20 to 45: 60 mg/m<sup>2</sup> IV or PO every other day | ||
− | + | ====CNS therapy==== | |
− | ==== | + | *[[Methotrexate (MTX)]] 15 mg IT (admixed with cytarabine) once per day on days 1, 5, 10, 15 |
− | *[[Methotrexate (MTX)]] 15 mg IT (admixed with | + | *[[Cytarabine (Ara-C)]] 40 mg IT (admixed with methotrexate) once per day on days 1, 5, 10, 15 |
− | *[[Cytarabine (Ara-C)]] 40 mg IT (admixed with | + | ====Supportive therapy==== |
− | + | *[[Leucovorin (Folinic acid)]] 25 mg PO every 6 hours for 3 days, initiated 24 hours after IV methotrexate administrations, and 10 mg PO every 6 hours for 2 days after IT methotrexate administrations | |
− | ====Supportive | ||
− | *[[Folinic acid | ||
− | |||
'''45-day course''' | '''45-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *EORTC 26952, patients achieving PR or CR: [[#Lomustine.2C_Methotrexate.2C_Procarbazine_2|Lomustine, methotrexate, procarbazine]] maintenance |
− | + | </div></div> | |
===References=== | ===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; [[Study_Groups#EORTC|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. [ | + | # '''EORTC 26952:''' Hoang-Xuan K, Taillandier L, Chinot O, Soubeyran P, Bogdhan U, Hildebrand J, Frenay M, De Beule N, Delattre JY, Baron B; [[Study_Groups#EORTC|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. [https://doi.org/10.1200/jco.2003.11.036 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12860951/ PubMed] |
− | + | ==MATRix-RICE {{#subobject:7b7ri0|Regimen=1}}== | |
− | == | + | MATRix-RICE: '''<u>M</u>'''ethotrexate, '''<u>A</u>'''ra-C (Cytarabine), '''<u>T</u>'''hiotepa, '''<u>Ri</u>'''tu'''<u>x</u>'''imab, followed by '''<u>R</u>'''ituximab, |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:cxjc04|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7844712/ Ferreri et al. 2021 (MARIETTA)] | ||
+ | |2015-03-30 to 2018-08-03 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, MATRix portion (cycles 1 to 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>) | ||
+ | *[[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 | ||
+ | ====Targeted therapy, MATRix portion (cycles 1 to 3)==== | ||
+ | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 0 | ||
+ | ====CNS therapy, MATRix portion (cycles 1 to 3)==== | ||
+ | *ONE of the following: | ||
+ | **[[Cytarabine liposomal (DepoCyt)]] 50 mg IT once on day 5 | ||
+ | **Triple therapy with [[Methotrexate (MTX)]] 12 mg; [[Cytarabine (Ara-C)]] 50 mg; [[Hydrocortisone (Cortef)]] 50 mg IT once on day 5 | ||
+ | ====Targeted therapy, RICE portion (cycles 4 to 6)==== | ||
+ | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Chemotherapy, RICE portion (cycles 4 to 6)==== | ||
+ | *[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 2 | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 2 | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3 | ||
+ | ====CNS therapy, RICE portion (cycles 4 to 6)==== | ||
+ | *ONE of the following: | ||
+ | **[[Cytarabine liposomal (DepoCyt)]] 50 mg IT once on day 4 | ||
+ | **Triple therapy with [[Methotrexate (MTX)]] 12 mg; [[Cytarabine (Ara-C)]] 50 mg; [[Hydrocortisone (Cortef)]] 50 mg IT once on day 4 | ||
+ | ====Supportive therapy, RICE portion (cycles 4 to 6)==== | ||
+ | *[[Mesna (Mesnex)]] | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#BCNU.2FTT.2C_then_auto_HSCT|Carmustine & Thiotepa with auto HSCT]] consolidation | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''MARIETTA:''' Ferreri AJM, Doorduijn JK, Re A, Cabras MG, Smith J, Ilariucci F, Luppi M, Calimeri T, Cattaneo C, Khwaja J, Botto B, Cellini C, Nassi L, Linton K, McKay P, Olivieri J, Patti C, Re F, Fanni A, Singh V, Bromberg JEC, Cozens K, Gastaldi E, Bernardi M, Cascavilla N, Davies A, Fox CP, Frezzato M, Osborne W, Liberati AM, Novak U, Zambello R, Zucca E, Cwynarski K; International Extranodal Lymphoma Study Group (IELSG). MATRix-RICE therapy and autologous haematopoietic stem-cell transplantation in diffuse large B-cell lymphoma with secondary CNS involvement (MARIETTA): an international, single-arm, phase 2 trial. Lancet Haematol. 2021 Feb;8(2):e110-e121. [https://doi.org/10.1016/s2352-3026(20)30366-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7844712/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33513372/ PubMed] [https://clinicaltrials.gov/study/NCT02329080 NCT02329080] | ||
− | === | + | ==Methotrexate-Cytarabine {{#subobject:f24bde|Regimen=1}}== |
− | {| class="wikitable" style="width: | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | !style="width: | + | ===Regimen {{#subobject:1d3fff|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2003.05.024 Abrey et al. 2003] |
− | |style="background-color:#91cf61"|Phase | + | |Not reported |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy, | + | ''Note: Patients proceed to part two 72 hours after 5th dose of MTX or once the 5th dose MTX level has cleared.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, first portion (cycles 1 to 5)==== | ||
*[[Methotrexate (MTX)]] 3500 mg/m<sup>2</sup> (maximum dose of 7000 mg) IV over 2 hours once on day 1 | *[[Methotrexate (MTX)]] 3500 mg/m<sup>2</sup> (maximum dose of 7000 mg) IV over 2 hours once on day 1 | ||
− | + | ====Supportive therapy, first portion (cycles 1 to 5)==== | |
− | ====Supportive | + | *[[Leucovorin (Folinic acid)]] 25 mg PO every 6 hours, beginning 24 hours after start of methotrexate, continued for 12 doses or until serum MTX level less than 100 nmol/L |
− | *[[Folinic acid | + | ====Chemotherapy, second portion (cycles 6 & 7)==== |
− | |||
− | |||
− | |||
− | |||
− | |||
− | ====Chemotherapy, | ||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 2 | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 2 | ||
− | + | ====Supportive therapy, second portion==== | |
− | ====Supportive | ||
*[[Filgrastim (Neupogen)]] as follows: | *[[Filgrastim (Neupogen)]] as follows: | ||
− | **Cycle | + | **Cycle 6: 10 mcg/kg SC once per day, starting on day 4 and continued until stem cell collection complete |
− | **Cycle | + | **Cycle 7: 5 mcg/kg SC once per day continued for 2 weeks or until ANC greater than 3000/μL |
− | + | '''14-day cycle for 5 cycles, then 1-month cycle for 2 cycles (stem cell collection took place between cycles 6 & 7)''' | |
− | '''1-month cycle for 2 cycles ( | + | </div> |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#BEAM.2C_then_auto_HSCT|BEAM, then autologous hematopoietic stem cell transplant]] | + | *[[#BEAM.2C_then_auto_HSCT|BEAM, then autologous hematopoietic stem cell transplant]] consolidation |
− | + | </div></div> | |
===References=== | ===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. [ | + | # 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. [https://doi.org/10.1200/jco.2003.05.024 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/14615443/ PubMed] |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | === | + | ==Methotrexate-Cytarabine & Thiotepa {{#subobject:990369|Regimen=1}}== |
− | {| class="wikitable" style="width: | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1 {{#subobject:e9fd90|Variant=1}}=== | ||
+ | {| class="wikitable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2006.06.2117 Illerhaus et al. 2006] | |[https://doi.org/10.1200/jco.2006.06.2117 Illerhaus et al. 2006] | ||
|1998-2003 | |1998-2003 | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy, | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy, MTX portion (course 1)==== | ||
*[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1, 10, 20 | *[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1, 10, 20 | ||
− | + | ====Supportive therapy, MTX portion (course 1)==== | |
− | ====Supportive | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> every 6 hours, beginning 24 hours after start of methotrexate, continuing until clearance |
− | *[[Folinic acid | ||
− | |||
− | |||
− | |||
''Patients with CR, PR, or SD "with clinical improvement" after the 2nd dose of MTX proceeded to:'' | ''Patients with CR, PR, or SD "with clinical improvement" after the 2nd dose of MTX proceeded to:'' | ||
− | ====Chemotherapy, stem cell mobilization==== | + | ====Chemotherapy, stem cell mobilization portion (course 2)==== |
− | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours once per day on days | + | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours once per day on days 2 & 3 |
− | *[[Thiotepa (Thioplex)]] 40 mg/m<sup>2</sup> (route not specified) once on day | + | *[[Thiotepa (Thioplex)]] 40 mg/m<sup>2</sup> (route not specified) once on day 3 |
− | + | '''28-day course, then 20-day course''' | |
− | '''20-day course''' | + | </div> |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then autologous hematopoietic stem cell transplant]] | + | *[[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then autologous hematopoietic stem cell transplant]] consolidation |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Protocol variant #2 {{#subobject:92e01d|Variant=1}}=== | ===Protocol variant #2 {{#subobject:92e01d|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.3324/haematol.11771 Illerhaus et al. 2008] |
− | |style="background-color:#ffffbe"|Pilot, | + | |2003-2006 |
+ | |style="background-color:#ffffbe"|Pilot, fewer than 20 patients | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy, part 1==== | ====Chemotherapy, part 1==== | ||
*[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once on day 1 | *[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> every 6 hours, beginning 24 hours after start of methotrexate, continuing until clearance |
− | *[[Folinic acid | ||
− | |||
'''10-day cycle for 2 to 4 cycles, followed by:''' | '''10-day cycle for 2 to 4 cycles, followed by:''' | ||
====Chemotherapy, part 2==== | ====Chemotherapy, part 2==== | ||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 2 | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 2 | ||
*[[Thiotepa (Thioplex)]] 40 mg/m<sup>2</sup> (route not specified) once on day 2 | *[[Thiotepa (Thioplex)]] 40 mg/m<sup>2</sup> (route not specified) once on day 2 | ||
− | |||
'''21-day cycle for 2 cycles (Stem cells are mobilized and collected after the first cycle)''' | '''21-day cycle for 2 cycles (Stem cells are mobilized and collected after the first cycle)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then autologous hematopoietic stem cell transplant]] | + | *[[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then autologous hematopoietic stem cell transplant]] consolidation |
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Presented in part at the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 10-13, 2005. --> | <!-- Presented in part at the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 10-13, 2005. --> | ||
− | # 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. [https://doi.org/10.1200/jco.2006.06.2117 link to original article] ''' | + | # 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. [https://doi.org/10.1200/jco.2006.06.2117 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16864853/ 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. [https://doi.org/10.1093/annonc/mds059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22473593 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. [https://doi.org/10.1093/annonc/mds059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22473593/ 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. [ | + | # 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. [https://doi.org/10.3324/haematol.11771 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18166803/ 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. [https://doi.org/10.1093/annonc/mds059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22473593 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. [https://doi.org/10.1093/annonc/mds059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22473593/ PubMed] |
− | |||
==Methotrexate & Rituximab {{#subobject:45f333|Regimen=1}}== | ==Methotrexate & Rituximab {{#subobject:45f333|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
===Regimen {{#subobject:715330|Variant=1}}=== | ===Regimen {{#subobject:715330|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940660/ Chamberlain et al. 2010] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940660/ Chamberlain et al. 2010] | ||
− | |style="background-color:#91cf61"|Phase | + | |2000-2007 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
''Note: the bounds as described in the paper do not account for the situation where CrCl = 60 mL/min/1.73m<sup>2</sup>.'' | ''Note: the bounds as described in the paper do not account for the situation where CrCl = 60 mL/min/1.73m<sup>2</sup>.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Methotrexate (MTX)]] | + | *[[Methotrexate (MTX)]] by the following renal function-based criteria: |
− | **CrCl | + | **CrCl more 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 | ||
− | |||
'''14-day cycle for 4 to 6 cycles''' | '''14-day cycle for 4 to 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *Chamberlain et al. 2010, patients with PR/CR: [[#Methotrexate_monotherapy_3|High-dose methotrexate]] consolidation |
− | + | </div></div> | |
===References=== | ===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. [ | + | # 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. Epub 2010 Feb 8. [https://doi.org/10.1093/neuonc/noq011 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940660/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20511181/ PubMed] |
− | |||
==MPV {{#subobject:245afd|Regimen=1}}== | ==MPV {{#subobject:245afd|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
MPV: '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rocarbazine, '''<u>V</u>'''incristine | MPV: '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rocarbazine, '''<u>V</u>'''incristine | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:2cb0c6|Variant=1}}=== | ===Regimen {{#subobject:2cb0c6|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable" style="width: 60%; text-align:center;" |
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/JCO.2000.18.17.3144 Abrey et al. 2000] | |[https://doi.org/10.1200/JCO.2000.18.17.3144 Abrey et al. 2000] | ||
− | | | + | |1992-1998 |
|style="background-color:#91cf61"|Non-randomized | |style="background-color:#91cf61"|Non-randomized | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2002.11.013 DeAngelis et al. 2002 (RTOG 93-10)] | |[https://doi.org/10.1200/jco.2002.11.013 DeAngelis et al. 2002 (RTOG 93-10)] | ||
− | |1993 | + | |1993 to not reported |
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 2500 mg/m<sup>2</sup> IV over 2 to 3 hours once on day 1 | *[[Methotrexate (MTX)]] 2500 mg/m<sup>2</sup> IV over 2 to 3 hours once on day 1 | ||
Line 676: | Line 707: | ||
**Cycles 1, 3, 5: 100 mg/m<sup>2</sup> PO once per day on days 1 to 7 | **Cycles 1, 3, 5: 100 mg/m<sup>2</sup> PO once per day on days 1 to 7 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once on day 1 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once on day 1 | ||
− | + | ====CNS therapy==== | |
− | ==== | ||
*[[Methotrexate (MTX)]] 12 mg IT once on day 8 (via Ommaya reservoir) | *[[Methotrexate (MTX)]] 12 mg IT once on day 8 (via Ommaya reservoir) | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Leucovorin (Folinic acid)]] as follows: |
− | *[[Folinic acid | + | **Days 2 to 4: 20 mg PO every 6 hours for 12 doses, '''beginning 24 hours after IV methotrexate administration''' |
− | **20 mg PO every 6 hours for 12 doses, beginning | + | **Days 8 & 9: 10 mg PO every 6 hours for 8 doses, '''beginning on the evening of IT methotrexate administration''' |
− | **10 mg PO every 6 hours for 8 doses, beginning | ||
*[[Dexamethasone (Decadron)]] as follows: | *[[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 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 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 | **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''' | '''14-day cycle for 5 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Whole_brain_irradiation|Whole-brain irradiation]] | + | *[[#Whole_brain_irradiation|Whole-brain irradiation]] consolidation |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol. 2000 Sep;18(17):3144-50. [https://doi.org/10.1200/JCO.2000.18.17.3144 link to original article] ''' | + | # Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol. 2000 Sep;18(17):3144-50. [https://doi.org/10.1200/JCO.2000.18.17.3144 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10963643/ 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. [https://doi.org/10.1200/JCO.2006.06.6910 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17008697 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. [https://doi.org/10.1200/JCO.2006.06.6910 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17008697/ 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. [https://doi.org/10.1200/jco.2002.11.013 link to original article] ''' | + | # '''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. [https://doi.org/10.1200/jco.2002.11.013 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12488408/ PubMed] |
− | |||
==MT-R {{#subobject:cc7d83|Regimen=1}}== | ==MT-R {{#subobject:cc7d83|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
MT-R: '''<u>M</u>'''ethotrexate, '''<u>T</u>'''emozolomide, '''<u>R</u>'''ituximab | MT-R: '''<u>M</u>'''ethotrexate, '''<u>T</u>'''emozolomide, '''<u>R</u>'''ituximab | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1 {{#subobject:5cf6d6|Variant=1}}=== | ===Regimen variant #1 {{#subobject:5cf6d6|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872318/ Glass et al. 2016 (RTOG 0227)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872318/ Glass et al. 2016 (RTOG 0227)] | ||
− | |style="background-color:#91cf61"|Phase | + | |Not reported |
+ | |style="background-color:#91cf61"|Phase 1/2 | ||
|- | |- | ||
|} | |} | ||
− | ''This is the MTD of this phase | + | ''Note: This is the MTD of this phase 1/2 trial; it appears that only a single dose of rituximab was given.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 3500 mg/m<sup>2</sup> IV once on day 1 | *[[Methotrexate (MTX)]] 3500 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Temozolomide (Temodar)]] as follows: | *[[Temozolomide (Temodar)]] as follows: | ||
**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 | ||
− | + | ====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 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Leucovorin (Folinic acid)]] 25 mg IV every 6 hours, starting 24 hours after methotrexate, continue until MTX level less than 100 nmol/L |
− | *[[Folinic acid | ||
− | |||
'''14-day cycle for 5 cycles''' | '''14-day cycle for 5 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Whole_brain_irradiation|WB-XRT | + | *[[#Whole_brain_irradiation|WB-XRT]] consolidation |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:5df6e6|Variant=1}}=== | ===Regimen variant #2 {{#subobject:5df6e6|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753699/ Rubenstein et al. 2013 (CALGB 50202)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753699/ Rubenstein et al. 2013 (CALGB 50202)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2004-2009 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once on day 1 | *[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once on day 1 | ||
*[[Temozolomide (Temodar)]] as follows: | *[[Temozolomide (Temodar)]] as follows: | ||
**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 | ||
− | + | ====Targeted therapy==== | |
*[[Rituximab (Rituxan)]] as follows: | *[[Rituximab (Rituxan)]] as follows: | ||
− | ** | + | **Cycles 1 to 6: 375 mg/m<sup>2</sup> IV once on day 3 |
− | + | ====Supportive therapy==== | |
− | + | *[[Leucovorin (Folinic acid)]] 100 mg/m<sup>2</sup> IV every 6 hours, start on day 2, continue until MTX level less than 50 nmol/L | |
− | ====Supportive | ||
− | *[[Folinic acid | ||
− | |||
'''14-day cycle for 7 cycles''' | '''14-day cycle for 7 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *CALGB 50202, patients achieving CR or CRu: [[#Cytarabine_.26_Etoposide_.28CYVE.29|CYVE]] consolidation |
+ | </div></div> | ||
===References=== | ===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 [ | + | # '''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. [https://doi.org/10.1200/jco.2012.46.9957 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753699/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23569323/ PubMed] [https://clinicaltrials.gov/study/NCT00098774 NCT00098774] |
− | # 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. [ | + | # '''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. [https://doi.org/10.1200/jco.2015.64.8634 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872318/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27022122/ PubMed] [https://clinicaltrials.gov/study/NCT00068250 NCT00068250] |
− | |||
==MVBP {{#subobject:891647|Regimen=1}}== | ==MVBP {{#subobject:891647|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
MVBP: '''<u>M</u>'''ethotrexate, '''<u>V</u>'''P16 (Etoposide), '''<u>B</u>'''CNU (Carmustine), Methyl'''<u>P</u>'''rednisolone | MVBP: '''<u>M</u>'''ethotrexate, '''<u>V</u>'''P16 (Etoposide), '''<u>B</u>'''CNU (Carmustine), Methyl'''<u>P</u>'''rednisolone | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:70497b|Variant=1}}=== | ===Regimen {{#subobject:70497b|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1038/sj.bmt.1705452 Colombat et al. 2006] |
− | |style="background-color:#91cf61"|Phase | + | |1999-2001 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 15 | *[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 15 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once on day 2 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once on day 2 | ||
*[[Carmustine (BCNU)]] 100 mg/m<sup>2</sup> IV once on day 3 | *[[Carmustine (BCNU)]] 100 mg/m<sup>2</sup> IV once on day 3 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Methylprednisolone (Solumedrol)]] 60 mg/m<sup>2</sup> (route not specified) once per day on days 1 to 5 | *[[Methylprednisolone (Solumedrol)]] 60 mg/m<sup>2</sup> (route not specified) once per day on days 1 to 5 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Leucovorin (Folinic acid)]] details not specified |
− | *[[Folinic acid | ||
− | |||
'''2 courses (length not specified), separated by 21 days''' | '''2 courses (length not specified), separated by 21 days''' | ||
− | + | ====CNS therapy==== | |
− | ==== | + | *[[Methotrexate (MTX)]] 20 mg IT (admixed with cytarabine and methylpredinsolone) |
− | *[[Methotrexate (MTX)]] 20 mg IT (admixed with | + | *[[Cytarabine (Ara-C)]] 50 mg IT (admixed with methotrexate and methylprednisolone) |
− | *[[Cytarabine (Ara-C)]] 50 mg IT (admixed with | + | *[[Methylprednisolone (Solumedrol)]] 40 mg IT (admixed with cytarabine and methotrexate) |
− | *[[Methylprednisolone (Solumedrol)]] 40 mg IT (admixed with | ||
− | |||
'''6 doses total (timing not specified)''' | '''6 doses total (timing not specified)''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *Colombat et al. 2006, responding patients (CR or PR): [[Stem_cell_mobilization_regimens#Cytarabine.2C_Ifosfamide.2C_G-CSF|Cytarabine & Ifosfamide]] for stem cell mobilization, then [[#BEAM.2C_then_auto_HSCT|BEAM, then autologous hematopoietic stem cell transplant]] consolidation |
− | * | + | *Colombat et al. 2006, non-responders: Salvage [[#Cytarabine_.26_Etoposide_.28CYVE.29|CYVE]] |
− | + | </div></div> | |
===References=== | ===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. [https:// | + | # 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. [https://doi.org/10.1038/sj.bmt.1705452 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16951691/ PubMed] |
− | |||
==Nordic Regimen, older patients {{#subobject:1778db|Regimen=1}}== | ==Nordic Regimen, older patients {{#subobject:1778db|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:eb66bd|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | + | !style="width: 33%"|Study | |
− | + | !style="width: 33%"|Dates of enrollment | |
− | === | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | {| class="wikitable" style="width: | ||
− | !style="width: | ||
− | !style="width: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380727/ Pulczynski et al. 2015 (NLGPCNSL)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380727/ Pulczynski et al. 2015 (NLGPCNSL)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2007-2010 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
− | + | ====Eligibility criteria==== | |
− | + | *Age 66-75 years | |
− | ==== | + | </div> |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy, A portion==== | ||
*[[Rituximab (Rituxan)]] as follows: | *[[Rituximab (Rituxan)]] as follows: | ||
− | **Cycle | + | **Cycle 1: 375 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once on day 1 | + | ====Chemotherapy, A portion==== |
+ | *[[Methotrexate (MTX)]] as follows: | ||
+ | **Cycles 1 & 4: 3000 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Ifosfamide (Ifex)]] as follows: | *[[Ifosfamide (Ifex)]] as follows: | ||
− | **Cycle | + | **Cycle 1: 800 mg/m<sup>2</sup> IV once per day on days 2 to 5 |
+ | ====Glucocorticoid therapy, A portion (cycles 1 & 4)==== | ||
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup>/day PO on days 2 to 5 | *[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup>/day PO on days 2 to 5 | ||
+ | ====CNS therapy, A portion (cycles 1 & 4)==== | ||
*[[Cytarabine liposomal (DepoCyt)]] 50 mg IT once on day 2 | *[[Cytarabine liposomal (DepoCyt)]] 50 mg IT once on day 2 | ||
− | + | ====Chemotherapy, B portion (cycles 2 & 5)==== | |
− | ====Chemotherapy, B cycles==== | ||
*[[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 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 150 mg/m<sup>2</sup> IV once per day on days 2 to 6 | ||
+ | ====Glucocorticoid therapy, B portion (cycles 2 & 5)==== | ||
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup>/day PO on days 2 to 5 | *[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup>/day PO on days 2 to 5 | ||
+ | ====CNS therapy, B portion (cycles 2 & 5)==== | ||
*[[Cytarabine liposomal (DepoCyt)]] 50 mg IT once on day 2 | *[[Cytarabine liposomal (DepoCyt)]] 50 mg IT once on day 2 | ||
− | + | ====Glucocorticoid therapy, C portion (cycles 3 & 6)==== | |
− | |||
− | ==== | ||
*[[Dexamethasone (Decadron)]] 20 mg/m<sup>2</sup>/day PO on days 3 to 7 | *[[Dexamethasone (Decadron)]] 20 mg/m<sup>2</sup>/day PO on days 3 to 7 | ||
+ | ====Chemotherapy, C portion (cycles 3 & 6)==== | ||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2 | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2 | ||
*[[Vindesine (Eldisine)]] 5 mg IV once on day 1 | *[[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)''' | '''21-day cycle for 6 cycles (A1, then B1, then C1, then A2, then B2, then C2)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Temozolomide_monotherapy|Temozolomide | + | *[[#Temozolomide_monotherapy|Temozolomide]] maintenance |
− | + | </div></div> | |
===References=== | ===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. [ | + | # '''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. [https://doi.org/10.3324/haematol.2014.108472 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380727/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25480497/ PubMed] [https://clinicaltrials.gov/study/NCT01458730 NCT01458730] |
− | |||
==Nordic Regimen, younger patients {{#subobject:e571ce|Regimen=1}}== | ==Nordic Regimen, younger patients {{#subobject:e571ce|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:2874b2|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | + | !style="width: 33%"|Study | |
− | + | !style="width: 33%"|Dates of enrollment | |
− | === | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | {| class="wikitable" style="width: | ||
− | !style="width: | ||
− | !style="width: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380727/ Pulczynski et al. 2015 (NLGPCNSL)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380727/ Pulczynski et al. 2015 (NLGPCNSL)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2007-2010 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
− | + | ====Eligibility criteria==== | |
− | + | *Age: 18 to 65 years | |
− | ==== | + | </div> |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy, A portion (cycles 1 & 4)==== | ||
*[[Rituximab (Rituxan)]] as follows: | *[[Rituximab (Rituxan)]] as follows: | ||
− | **Cycle | + | **Cycle 1: 375 mg/m<sup>2</sup> IV once on day 1 |
+ | ====Chemotherapy, A portion (cycles 1 & 4)==== | ||
*[[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 | ||
+ | ====Glucocorticoid therapy, A portion (cycles 1 & 4)==== | ||
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup>/day PO on days 2 to 5 | *[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup>/day PO on days 2 to 5 | ||
+ | ====CNS therapy, A portion (cycles 1 & 4)==== | ||
*[[Cytarabine liposomal (DepoCyt)]] 50 mg IT once on day 2 | *[[Cytarabine liposomal (DepoCyt)]] 50 mg IT once on day 2 | ||
− | + | ====Chemotherapy, B portion (cycles 2 & 5)==== | |
− | ====Chemotherapy, B cycles==== | ||
*[[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 | ||
+ | *[[Vincristine (Oncovin)]] 2 mg IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV once per day on days 2 to 5 | ||
+ | ====Glucocorticoid therapy, B portion (cycles 2 & 5)==== | ||
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup>/day PO on days 2 to 5 | *[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup>/day PO on days 2 to 5 | ||
− | + | ====CNS therapy, B portion (cycles 2 & 5)==== | |
*[[Cytarabine liposomal (DepoCyt)]] 50 mg IT once on day 2 | *[[Cytarabine liposomal (DepoCyt)]] 50 mg IT once on day 2 | ||
− | + | ====Glucocorticoid therapy, C portion (cycles 3 & 6)==== | |
− | |||
− | ==== | ||
*[[Dexamethasone (Decadron)]] 20 mg/m<sup>2</sup>/day PO on days 3 to 7 | *[[Dexamethasone (Decadron)]] 20 mg/m<sup>2</sup>/day PO on days 3 to 7 | ||
+ | ====Chemotherapy, C portion (cycles 3 & 6)==== | ||
*[[Cytarabine (Ara-C)]] 1500 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2 | *[[Cytarabine (Ara-C)]] 1500 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2 | ||
*[[Vindesine (Eldisine)]] 5 mg IV once on day 1 | *[[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)''' | '''21-day cycle for 6 cycles (A1, then B1, then C1, then A2, then B2, then C2)''' | ||
− | + | </div></div> | |
===References=== | ===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. [ | + | # '''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. [https://doi.org/10.3324/haematol.2014.108472 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380727/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25480497/ PubMed] [https://clinicaltrials.gov/study/NCT01458730 NCT01458730] |
==R-MCP (CCNU) {{#subobject:58966e|Regimen=1}}== | ==R-MCP (CCNU) {{#subobject:58966e|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
R-MCP: '''<u>R</u>'''ituximab, '''<u>M</u>'''ethotrexate, '''<u>C</u>'''CNU (Lomustine), '''<u>P</u>'''rocarbazine | R-MCP: '''<u>R</u>'''ituximab, '''<u>M</u>'''ethotrexate, '''<u>C</u>'''CNU (Lomustine), '''<u>P</u>'''rocarbazine | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:6b72ea|Variant=1}}=== | ===Regimen {{#subobject:6b72ea|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1093/annonc/mdq712 Fritsch et al. 2011] | |[https://doi.org/10.1093/annonc/mdq712 Fritsch et al. 2011] | ||
− | |style="background-color:#91cf61"|Phase | + | |2005-2009 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
''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.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====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 | ||
*[[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 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Leucovorin (Folinic acid)]] (dose/route not specified) every 6 hours beginning 24 hours after start of MTX infusion, continued for 3 days or until clearance |
− | *[[Folinic acid | ||
− | |||
'''43-day cycle for up to 3 cycles''' | '''43-day cycle for up to 3 cycles''' | ||
− | + | </div></div> | |
===References=== | ===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. [https://doi.org/10.1093/annonc/mdq712 link to original article] ''' | + | # 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. [https://doi.org/10.1093/annonc/mdq712 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21303800/ PubMed] |
− | |||
==R-MP {{#subobject:58b4a9|Regimen=1}}== | ==R-MP {{#subobject:58b4a9|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
R-MP: '''<u>R</u>'''ituximab, '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rocarbazine | R-MP: '''<u>R</u>'''ituximab, '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rocarbazine | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:6ea131|Variant=1}}=== | ===Regimen {{#subobject:6ea131|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383936/ Fritsch et al. 2016 (PRIMAIN)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383936/ Fritsch et al. 2016 (PRIMAIN)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2009-2013 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====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 | ||
− | *[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day | + | ====Chemotherapy==== |
+ | *[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day 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 | ||
− | |||
'''42-day cycle for 3 cycles''' | '''42-day cycle for 3 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Procarbazine_monotherapy|Procarbazine | + | *[[#Procarbazine_monotherapy|Procarbazine]] maintenance |
− | + | </div></div> | |
===References=== | ===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. [https:// | + | # '''PRIMAIN:''' 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. [https://doi.org/10.1038/leu.2016.334 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383936/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27843136/ PubMed] [https://clinicaltrials.gov/study/NCT00989352 NCT00989352] |
+ | #'''PRIMA-CNS:''' DRKS00024085 | ||
==R-MPV {{#subobject:5ca49d|Regimen=1}}== | ==R-MPV {{#subobject:5ca49d|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
R-MPV: '''<u>R</u>'''ituximab, '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rocarbazine, '''<u>V</u>'''incristine | R-MPV: '''<u>R</u>'''ituximab, '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rocarbazine, '''<u>V</u>'''incristine | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:ac140a|Variant=1}}=== | ===Regimen {{#subobject:ac140a|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable" style="width: 60%; text-align:center;" |
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://doi.org/10.1200/jco.2007.12.5062 Shah et al. 2007] | + | |[https://doi.org/10.1200/jco.2007.12.5062 Shah et al. 2007 (MSK 01-146)] |
|2002-2005 | |2002-2005 | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342354/ Omuro et al. 2015 (MSK 04-129)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342354/ Omuro et al. 2015 (MSK 04-129)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2005-2011 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====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: | ||
**Odd cycles: 100 mg/m<sup>2</sup> PO once per day on days 1 to 7 | **Odd cycles: 100 mg/m<sup>2</sup> PO once per day on days 1 to 7 | ||
− | |||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once on day 2 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once on day 2 | ||
− | + | ====CNS therapy==== | |
− | ==== | + | *''(only described in MSK 01-146)'' |
− | *''(only described in | ||
*[[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 therapy==== | |
− | ====Supportive | + | *[[Leucovorin (Folinic acid)]] 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 administration |
− | *[[Folinic acid | ||
− | |||
'''14-day cycle for 5 to 7 cycles''' | '''14-day cycle for 5 to 7 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *MSK 01-146: [[#Whole_brain_irradiation|whole-brain irradiation]] consolidation, in 3 to 5 weeks |
− | * | + | *MSK 04-129: [[#Bu.2FTT.2FCy.2C_then_auto_HSCT|Bu/TT/Cy, then autologous hematopoietic stem cell transplant]] consolidation, after 5 cycles if CR achieved, or after 7 cycles for PR/CR at that time |
− | + | </div></div> | |
===References=== | ===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. [https://doi.org/10.1200/jco.2007.12.5062 link to original article] ''' | + | # '''MSK 01-146:''' 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. [https://doi.org/10.1200/jco.2007.12.5062 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17947720/ PubMed] [https://clinicaltrials.gov/study/NCT00594815 NCT00594815] |
− | ## '''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. [ | + | ## '''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. [https://doi.org/10.1200/jco.2013.50.4910 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24101038/ 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. [ | + | # '''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. [https://doi.org/10.1182/blood-2014-10-604561 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342354/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25568347/ PubMed] [https://clinicaltrials.gov/study/NCT00596154 NCT00596154] |
− | |||
− | |||
+ | =Consolidation after upfront therapy= | ||
==BCNU/TT, then auto HSCT {{#subobject:a7b7ae|Regimen=1}}== | ==BCNU/TT, then auto HSCT {{#subobject:a7b7ae|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
BCNU/TT: '''<u>BCNU</u>''' (Carmustine), '''<u>T</u>'''hio'''<u>T</u>'''epa | BCNU/TT: '''<u>BCNU</u>''' (Carmustine), '''<u>T</u>'''hio'''<u>T</u>'''epa | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1 {{#subobject:81ede7|Variant=1}}=== | ===Regimen variant #1 {{#subobject:81ede7|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable" style="width: 60%; text-align:center;" |
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2006.06.2117 Illerhaus et al. 2006] | |[https://doi.org/10.1200/jco.2006.06.2117 Illerhaus et al. 2006] | ||
|1998-2003 | |1998-2003 | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|- | |- | ||
|} | |} | ||
''Note that the day count starts from the very beginning of treatment.'' | ''Note that the day count starts from the very beginning of treatment.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Methotrexate | + | *[[#Methotrexate-Cytarabine_.26_Thiotepa|High-dose methotrexate, then Ara-C & Thiotepa]] induction |
− | + | </div> | |
− | + | {{#lst:Autologous HSCT|81ede7}} | |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Whole_brain_irradiation|Whole-brain irradiation]] | + | *[[#Whole_brain_irradiation|Whole-brain irradiation]] consolidation |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:769950|Variant=1}}=== | ===Regimen variant #2 {{#subobject:769950|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.3324/haematol.11771 Illerhaus et al. 2008] |
− | |style="background-color:#ffffbe"|Pilot, | + | |2003-2006 |
+ | |style="background-color:#ffffbe"|Pilot, fewer than 20 patients | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Methotrexate | + | *[[#Methotrexate-Cytarabine_.26_Thiotepa|High-dose methotrexate, then Ara-C & Thiotepa]] induction |
− | + | </div> | |
− | + | {{#lst:Autologous HSCT|769950}} | |
− | + | </div> | |
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
<!-- Presented in part at the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 10-13, 2005. --> | <!-- Presented in part at the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 10-13, 2005. --> | ||
− | # 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. [https://doi.org/10.1200/jco.2006.06.2117 link to original article] ''' | + | # 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. [https://doi.org/10.1200/jco.2006.06.2117 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16864853/ 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. [https://doi.org/10.1093/annonc/mds059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22473593 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. [https://doi.org/10.1093/annonc/mds059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22473593/ 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. [ | + | # 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. [https://doi.org/10.3324/haematol.11771 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18166803/ 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. [https://doi.org/10.1093/annonc/mds059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22473593 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. [https://doi.org/10.1093/annonc/mds059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22473593/ 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. [https:// | + | # '''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. [https://doi.org/10.1016/S2352-3026(16)00036-3 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27132696/ PubMed] [https://clinicaltrials.gov/study/NCT01011920 NCT01011920] |
− | ## '''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. [https:// | + | ## '''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. [https://doi.org/10.1016/S2352-3026(17)30174-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29054815/ PubMed] |
==BEAM, then auto HSCT {{#subobject:c9216e|Regimen=1}}== | ==BEAM, then auto HSCT {{#subobject:c9216e|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
BEAM: '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | BEAM: '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1 {{#subobject:bbc83f|Variant=1}}=== | ===Regimen variant #1 {{#subobject:bbc83f|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1038/sj.bmt.1705452 Colombat et al. 2006] |
− | |style="background-color:#91cf61"|Phase | + | |1999-2001 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#MVBP|MVBP]] x 2 | + | *[[#MVBP|MVBP]] induction x 2 |
− | + | </div> | |
− | + | {{#lst:Autologous HSCT|bbc83f}} | |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | |||
− | |||
− | |||
− | |||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Whole_brain_irradiation|Whole-brain irradiation]] | + | *[[#Whole_brain_irradiation|Whole-brain irradiation]] consolidation |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:5bf047|Variant=1}}=== | ===Regimen variant #2 {{#subobject:5bf047|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2003.05.024 Abrey et al. 2003] |
− | |style="background-color:#91cf61"|Phase | + | |Not reported |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Methotrexate | + | *[[#Methotrexate-Cytarabine|Methotrexate, then Cytarabine]] induction |
− | + | </div> | |
− | + | {{#lst:Autologous HSCT|16f7a3}} | |
− | + | </div> | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
===References=== | ===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. [ | + | # 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. [https://doi.org/10.1200/jco.2003.05.024 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/14615443/ 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. [https:// | + | # 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. [https://doi.org/10.1038/sj.bmt.1705452 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16951691/ PubMed] |
==Bu/TT, then auto HSCT {{#subobject:e04a91|Regimen=1}}== | ==Bu/TT, then auto HSCT {{#subobject:e04a91|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Bu/TT: '''<u>Bu</u>'''sulfan, '''<u>T</u>'''hio'''<u>T</u>'''epa | Bu/TT: '''<u>Bu</u>'''sulfan, '''<u>T</u>'''hio'''<u>T</u>'''epa | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:df1bb4|Variant=1}}=== | ===Regimen {{#subobject:df1bb4|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1093/annonc/mdl458 Montemurro et al. 2007 (OSHO-53)] | |[https://doi.org/10.1093/annonc/mdl458 Montemurro et al. 2007 (OSHO-53)] | ||
− | |style="background-color:#91cf61"|Phase | + | |1999-2004 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Methotrexate_monotherapy_2|High-dose methotrexate]] x 2 | + | *[[#Methotrexate_monotherapy_2|High-dose methotrexate]] induction x 2 |
− | + | </div> | |
− | + | {{#lst:Autologous HSCT|df1bb4}} | |
− | + | </div> | |
− | |||
− | |||
− | |||
===References=== | ===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. [https://doi.org/10.1093/annonc/mdl458 link to original article] ''' | + | # '''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. [https://doi.org/10.1093/annonc/mdl458 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17185743/ PubMed] |
==Bu/TT/Cy, then auto HSCT {{#subobject:e04a91|Regimen=1}}== | ==Bu/TT/Cy, then auto HSCT {{#subobject:e04a91|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Bu/TT/Cy: '''<u>Bu</u>'''sulfan, '''<u>T</u>'''hio'''<u>T</u>'''epa, '''<u>Cy</u>'''clophosphamide | Bu/TT/Cy: '''<u>Bu</u>'''sulfan, '''<u>T</u>'''hio'''<u>T</u>'''epa, '''<u>Cy</u>'''clophosphamide | ||
− | + | <br>TBC: '''<u>T</u>'''hiotepa, '''<u>B</u>'''usulfan, '''<u>C</u>'''yclophosphamide | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:df1bb4|Variant=1}}=== | ===Regimen {{#subobject:df1bb4|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342354/ Omuro et al. 2015 (MSK 04-129)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342354/ Omuro et al. 2015 (MSK 04-129)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2005-2011 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#R-MPV|R-MPV]] | + | *[[#R-MPV|R-MPV]] induction |
− | + | </div> | |
− | + | {{#lst:Autologous HSCT|df1bb5}} | |
− | + | </div> | |
− | |||
− | |||
− | |||
− | |||
===References=== | ===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. [ | + | # '''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. [https://doi.org/10.1182/blood-2014-10-604561 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342354/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25568347/ PubMed] [https://clinicaltrials.gov/study/NCT00596154 NCT00596154] |
− | ==HiDAC {{#subobject:25959d|Regimen=1}}== | + | ==High-dose Cytarabine monotherapy (HiDAC) {{#subobject:25959d|Regimen=1}}== |
− | |||
− | |||
− | |||
− | |||
HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:4d5aee|Variant=1}}=== | ===Regimen {{#subobject:4d5aee|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable" style="width: 60%; text-align:center;" |
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/JCO.2000.18.17.3144 Abrey et al. 2000] | |[https://doi.org/10.1200/JCO.2000.18.17.3144 Abrey et al. 2000] | ||
− | | | + | |1992-1998 |
|style="background-color:#91cf61"|Non-randomized | |style="background-color:#91cf61"|Non-randomized | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2002.11.013 DeAngelis et al. 2002 (RTOG 93-10)] | |[https://doi.org/10.1200/jco.2002.11.013 DeAngelis et al. 2002 (RTOG 93-10)] | ||
− | |1993 | + | |1993 to not reported |
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|- | |- | ||
|} | |} | ||
''Time interval of cycles is not explicitly described and is derived from Table 1 in DeAngelis et al. 2002.'' | ''Time interval of cycles is not explicitly described and is derived from Table 1 in DeAngelis et al. 2002.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Whole_brain_irradiation|Whole-brain irradiation]] x | + | *Definitive [[#Whole_brain_irradiation|Whole-brain irradiation]] x 4500 cGy |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 & 2 | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 & 2 | ||
− | |||
'''21-day cycle for 2 cycles''' | '''21-day cycle for 2 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol. 2000 Sep;18(17):3144-50. [https://doi.org/10.1200/JCO.2000.18.17.3144 link to original article] ''' | + | # Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol. 2000 Sep;18(17):3144-50. [https://doi.org/10.1200/JCO.2000.18.17.3144 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10963643/ 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. [https://doi.org/10.1200/JCO.2006.06.6910 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17008697 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. [https://doi.org/10.1200/JCO.2006.06.6910 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17008697/ 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. [https://doi.org/10.1200/jco.2002.11.013 link to original article] ''' | + | # '''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. [https://doi.org/10.1200/jco.2002.11.013 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12488408/ PubMed] |
− | + | ==Cytarabine & Etoposide (CYVE) {{#subobject:b2c919|Regimen=1}}== | |
− | ==CYVE {{#subobject:b2c919|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CYVE: '''<u>CY</u>'''tarabine & '''<u>VE</u>'''pesid (Etoposide) | CYVE: '''<u>CY</u>'''tarabine & '''<u>VE</u>'''pesid (Etoposide) | ||
<br>EA: '''<u>E</u>'''toposide & '''<u>A</u>'''ra-C (Cytarabine) | <br>EA: '''<u>E</u>'''toposide & '''<u>A</u>'''ra-C (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:4df5e6|Variant=1}}=== | ===Regimen {{#subobject:4df5e6|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753699/ Rubenstein et al. 2013 (CALGB 50202)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753699/ Rubenstein et al. 2013 (CALGB 50202)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2004-2009 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#MT-R|MT-R | + | *[[#MT-R|MT-R]] induction |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 2 hours every 12 hours on days 1 to 4 (total dose: 16,000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 2 hours every 12 hours on days 1 to 4 (total dose: 16,000 mg/m<sup>2</sup>) | ||
*[[Etoposide (Vepesid)]] 10 mg/kg/day IV continuous infusion over 96 hours, started on day 1 (total dose: 40 mg/kg) | *[[Etoposide (Vepesid)]] 10 mg/kg/day IV continuous infusion over 96 hours, started on day 1 (total dose: 40 mg/kg) | ||
− | |||
'''4-day course''' | '''4-day course''' | ||
− | + | </div></div> | |
===References=== | ===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 [ | + | # '''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. [https://doi.org/10.1200/jco.2012.46.9957 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753699/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23569323/ PubMed] [https://clinicaltrials.gov/study/NCT00098774 NCT00098774] |
− | |||
==Lomustine, Methotrexate, Procarbazine {{#subobject:7f4fbe|Regimen=1}}== | ==Lomustine, Methotrexate, Procarbazine {{#subobject:7f4fbe|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
===Regimen {{#subobject:156623|Variant=1}}=== | ===Regimen {{#subobject:156623|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2003.11.036 Hoang-Xuan et al. 2003 (EORTC 26952)] |
− | |style="background-color:#91cf61"|Phase | + | |1997-1999 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ====Preceding treatment==== | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[#Lomustine.2C_Methotrexate.2C_Procarbazine.2C_Methylprednisolone.2C|Lomustine, Methotrexate, Procarbazine, Methylprednisolone | + | ====Preceding treatment==== |
+ | *[[#Lomustine.2C_Methotrexate.2C_Procarbazine.2C_Methylprednisolone.2C|Lomustine, Methotrexate, Procarbazine, Methylprednisolone]] induction | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 1000 mg/m<sup>2</sup> IV once on day 1 | *[[Methotrexate (MTX)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Lomustine (CCNU)]] 40 mg/m<sup>2</sup> PO once on day 1 | *[[Lomustine (CCNU)]] 40 mg/m<sup>2</sup> PO once on day 1 | ||
*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 7 | *[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 7 | ||
− | + | ====CNS therapy==== | |
− | ==== | + | *[[Methotrexate (MTX)]] 15 mg IT (admixed with cytarabine) once on day 1 |
− | *[[Methotrexate (MTX)]] 15 mg IT (admixed with | + | *[[Cytarabine (Ara-C)]] 40 mg IT (admixed with methotrexate) once on day 1 |
− | *[[Cytarabine (Ara-C)]] 40 mg IT (admixed with | + | ====Supportive therapy==== |
− | + | *[[Leucovorin (Folinic acid)]] 25 mg PO every 6 hours for 3 days, initiated 24 hours after IV methotrexate administration | |
− | ====Supportive | ||
− | *[[Folinic acid | ||
− | |||
'''42-day cycle for 5 cycles''' | '''42-day cycle for 5 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Hoang-Xuan K, Taillandier L, Chinot O, Soubeyran P, Bogdhan U, Hildebrand J, Frenay M, De Beule N, Delattre JY, Baron B; [[Study_Groups#EORTC|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. [ | + | # Hoang-Xuan K, Taillandier L, Chinot O, Soubeyran P, Bogdhan U, Hildebrand J, Frenay M, De Beule N, Delattre JY, Baron B; [[Study_Groups#EORTC|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. [https://doi.org/10.1200/jco.2003.11.036 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12860951/ PubMed] |
− | |||
==Methotrexate monotherapy {{#subobject:66ffbb|Regimen=1}}== | ==Methotrexate monotherapy {{#subobject:66ffbb|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
===Regimen variant #1 {{#subobject:f64ee1|Variant=1}}=== | ===Regimen variant #1 {{#subobject:f64ee1|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940660/ Chamberlain et al. 2010] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940660/ Chamberlain et al. 2010] | ||
− | |style="background-color:#91cf61"|Phase | + | |2000-2007 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
''Note: the bounds as described in the paper do not account for the situation where CrCl = 60 mL/min/1.73m<sup>2</sup>.'' | ''Note: the bounds as described in the paper do not account for the situation where CrCl = 60 mL/min/1.73m<sup>2</sup>.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Methotrexate_.26_Rituximab|High-dose methotrexate & Rituximab]] | + | *[[#Methotrexate_.26_Rituximab|High-dose methotrexate & Rituximab]] induction |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Methotrexate (MTX)]] | + | *[[Methotrexate (MTX)]] by the following renal function-based criteria: |
− | **CrCl | + | **CrCl more 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 | ||
− | |||
'''28-day cycle for 4 cycles''' | '''28-day cycle for 4 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:c0f639|Variant=1}}=== | ===Regimen variant #2 {{#subobject:c0f639|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2003.03.036 Batchelor et al. 2003 (NABTT 96-07)] |
− | |style="background-color:#91cf61"|Phase | + | |1998-1999 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Methotrexate_monotherapy_2|High-dose methotrexate | + | *[[#Methotrexate_monotherapy_2|High-dose methotrexate]] induction |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Methotrexate (MTX)]] 8000 mg/m<sup>2</sup> IV over 4 hours once on day 1 | + | *[[Methotrexate (MTX)]] by the following renal function-based criteria: |
− | ** | + | **CrCl 100 mL/min/1.73m<sup>2</sup> or more: 8000 mg/m<sup>2</sup> IV over 4 hours once on day 1 |
− | + | **CrCl less than 100 mL/min/1.73m<sup>2</sup>: The dose was reduced by the percentage reduction below 100. For example, a CrCl of 50 mL/min/1.73m<sup>2</sup> would mandate a 50% dose reduction to 4000 mg/m<sup>2</sup>. | |
'''28-day cycle for 11 cycles''' | '''28-day cycle for 11 cycles''' | ||
− | + | </div></div> | |
===References=== | ===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. [ | + | # 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. [https://doi.org/10.1200/jco.2003.03.036 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12637469/ 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. [ | + | # 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. Epub 2010 Feb 8. [https://doi.org/10.1093/neuonc/noq011 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940660/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20511181/ PubMed] |
− | |||
==Procarbazine monotherapy {{#subobject:37e11d|Regimen=1}}== | ==Procarbazine monotherapy {{#subobject:37e11d|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:13bae4|Variant=1}}=== | ===Regimen {{#subobject:13bae4|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383936/ Fritsch et al. 2016 (PRIMAIN)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383936/ Fritsch et al. 2016 (PRIMAIN)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2009-2013 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#R-MP|R-MP]] x 3 | + | *Induction [[#R-MP|R-MP]] x 3 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Procarbazine (Matulane)]] 100 mg PO once per day on days 1 to 5 | *[[Procarbazine (Matulane)]] 100 mg PO once per day on days 1 to 5 | ||
− | |||
'''28-day cycle for 6 cycles''' | '''28-day cycle for 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===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. [https:// | + | # '''PRIMAIN:''' 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. [https://doi.org/10.1038/leu.2016.334 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383936/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27843136/ PubMed] [https://clinicaltrials.gov/study/NCT00989352 NCT00989352] |
− | |||
==Temozolomide monotherapy {{#subobject:5c7608|Regimen=1}}== | ==Temozolomide monotherapy {{#subobject:5c7608|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
===Regimen variant #1 {{#subobject:5cf6d6|Variant=1}}=== | ===Regimen variant #1 {{#subobject:5cf6d6|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872318/ Glass et al. 2016 (RTOG 0227)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872318/ Glass et al. 2016 (RTOG 0227)] | ||
− | |style="background-color:#91cf61"|Phase | + | |Not reported |
+ | |style="background-color:#91cf61"|Phase 1/2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Whole_brain_irradiation|WB-XRT | + | *[[#Whole_brain_irradiation|WB-XRT]] consolidation |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Temozolomide (Temodar)]] as follows: | *[[Temozolomide (Temodar)]] as follows: | ||
**Week 14: 200 mg/m<sup>2</sup> PO once per day for 5 days (150 mg/m<sup>2</sup> allowed) | **Week 14: 200 mg/m<sup>2</sup> PO once per day for 5 days (150 mg/m<sup>2</sup> allowed) | ||
**Weeks 18, 22, 26, 30, 34, 38, 42, 46, 50: 200 mg/m<sup>2</sup> PO once per day for 5 days | **Weeks 18, 22, 26, 30, 34, 38, 42, 46, 50: 200 mg/m<sup>2</sup> PO once per day for 5 days | ||
− | + | '''50-week course''' | |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:084bc7|Variant=1}}=== | ===Regimen variant #2 {{#subobject:084bc7|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380727/ Pulczynski et al. 2015 (NLGPCNSL)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380727/ Pulczynski et al. 2015 (NLGPCNSL)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2007-2010 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Nordic_Regimen.2C_older_patients|Nordic Regimen for older patients]] | + | *[[#Nordic_Regimen.2C_older_patients|Nordic Regimen for older patients]] induction |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Temozolomide (Temodar)]] 150 mg/m<sup>2</sup>/day PO on days 1 to 5 | *[[Temozolomide (Temodar)]] 150 mg/m<sup>2</sup>/day PO on days 1 to 5 | ||
− | |||
'''28-day cycle for up to 13 cycles (1 year)''' | '''28-day cycle for up to 13 cycles (1 year)''' | ||
− | + | </div></div> | |
===References=== | ===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. [ | + | # '''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. [https://doi.org/10.3324/haematol.2014.108472 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380727/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25480497/ PubMed] [https://clinicaltrials.gov/study/NCT01458730 NCT01458730] |
− | # 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. [ | + | # '''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. [https://doi.org/10.1200/jco.2015.64.8634 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872318/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27022122/ PubMed] [https://clinicaltrials.gov/study/NCT00068250 NCT00068250] |
− | |||
==Whole brain irradiation {{#subobject:6115dc|Regimen=1}}== | ==Whole brain irradiation {{#subobject:6115dc|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
WBRT: '''<u>W</u>'''hole-'''<u>B</u>'''rain '''<u>R</u>'''adiation '''<u>T</u>'''herapy | WBRT: '''<u>W</u>'''hole-'''<u>B</u>'''rain '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
− | ===Regimen variant #1, | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #1, 2340 cGy {{#subobject:a6ae7a|Variant=1}}=== |
+ | {| class="wikitable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://doi.org/10.1200/jco.2007.12.5062 Shah et al. 2007] | + | |[https://doi.org/10.1200/jco.2007.12.5062 Shah et al. 2007 (MSK 01-146)] |
|2002-2005 | |2002-2005 | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#R-MPV|R-MPV]] x 5 to 7 cycles, with complete response | + | *Induction [[#R-MPV|R-MPV]] x 5 to 7 cycles, with complete response |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Whole-brain irradiation]] to | + | *[[External_beam_radiotherapy|Whole-brain irradiation]] to 2340 cGy in 1.8000 cGy fractions |
− | + | </div></div><br> | |
− | ===Regimen variant #2, | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #2, 3000 cGy {{#subobject:8ca014|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1038/sj.bmt.1705452 Colombat et al. 2006] | ||
+ | |1999-2001 | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https://www. | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076938/ Mishima et al. 2023 (JCOG1114C)] |
− | |style="background-color:# | + | |2014-09-20 to 2018-08-24 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Temozolomide_.26_RT_999|Temozolomide & WBRT]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior OS<br>OS24: 86.8% vs 71.4%<br>(HR 0.46, 95% CI 0.20-1.05) | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#BEAM.2C_then_auto_HSCT|BEAM, then autologous hematopoietic stem cell transplant]], with complete response | + | *Colombat et al. 2006: [[#BEAM.2C_then_auto_HSCT|BEAM, then autologous hematopoietic stem cell transplant]] consolidation, with complete response |
+ | *JCOG1114C: [[#Methotrexate_monotherapy_2|HD-MTX]] induction | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Whole-brain irradiation]] to | + | *[[External_beam_radiotherapy|Whole-brain irradiation]] to 3000 cGy in 1.8000 cGy fractions |
− | + | </div></div><br> | |
− | ===Regimen variant #3, | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #3, 3000 cGy + 1000 cGy boost {{#subobject:b8264a|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1038/sj.bmt.1705452 Colombat et al. 2006] | ||
+ | |1999-2001 | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https://www. | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076938/ Mishima et al. 2023 (JCOG1114C)] |
− | |style="background-color:# | + | |2014-09-20 to 2018-08-24 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Temozolomide_.26_RT_999|Temozolomide & WBRT]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior OS<br>OS24: 86.8% vs 71.4%<br>(HR 0.46, 95% CI 0.20-1.05) | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: boost was optional in JCOG1114C.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#BEAM.2C_then_auto_HSCT|BEAM, then autologous hematopoietic stem cell transplant]], with partial response | + | *Colombat et al. 2006: [[#BEAM.2C_then_auto_HSCT|BEAM, then autologous hematopoietic stem cell transplant]] consolidation, with partial response |
+ | *JCOG1114C: [[#Methotrexate_monotherapy_2|HD-MTX]] induction | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Whole-brain irradiation]] to | + | *[[External_beam_radiotherapy|Whole-brain irradiation]] to 3000 cGy in 1.8000 cGy fractions plus 1000 cGy boost to the tumor bed |
− | + | </div></div><br> | |
− | ===Regimen variant #4, | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ===Regimen variant #4, 3600 cGy {{#subobject:d477fd|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872318/ Glass et al. 2016 (RTOG 0227)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872318/ Glass et al. 2016 (RTOG 0227)] | ||
− | |style="background-color:#91cf61"|Phase | + | |Not reported |
+ | |style="background-color:#91cf61"|Phase 1/2 | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S2352-3026(16)00036-3 Ferreri et al. 2016 (IELSG32)] |
− | |style="background-color:#1a9851"|Randomized Phase | + | |2010-2014 |
+ | |style="background-color:#1a9851"|Randomized Phase 2 (C) | ||
|[[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then auto HSCT]] | |[[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then auto HSCT]] | ||
− | |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS24 | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS24<sup>1</sup> |
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for IELSG32 is based on the 2017 update.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *RTOG 0227: [[#MT-R|MT-R | + | *RTOG 0227: [[#MT-R|MT-R]] induction |
− | *IELSG32: [[#CYM | + | *IELSG32: [[#Cytarabine_.26_Methotrexate_.28CYM.29|CYM]] versus [[#Cytarabine.2C_Methotrexate.2C_Rituximab|Cytarabine, MTX, Rituximab]] versus [[#MATRix|MATRix]] induction, with complete response |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Whole-brain irradiation]] to | + | *[[External_beam_radiotherapy|Whole-brain irradiation]] to 3600 cGy by the following study-specific criteria: |
− | **RTOG 0227: | + | **RTOG 0227: 120 cGy twice per day fractions on weeks 11 to 13 |
− | **IELSG32: 1. | + | **IELSG32: 1.8000 cGy fractions |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *RTOG 0227: [[#Temozolomide_monotherapy|Temozolomide | + | *RTOG 0227: [[#Temozolomide_monotherapy|Temozolomide]] consolidation |
− | + | </div></div><br> | |
− | ===Regimen variant #5, | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ===Regimen variant #5, 3600 cGy + 900 cGy boost {{#subobject:d377ed|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(09)61416-1 Ferreri et al. 2009 (IELSG20)] |
− | |style="background-color:#91cf61"|Non-randomized | + | |2004-2007 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 2 RCT | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S2352-3026(16)00036-3 Ferreri et al. 2016 (IELSG32)] |
− | |style="background-color:#1a9851"|Randomized Phase | + | |2010-2014 |
+ | |style="background-color:#1a9851"|Randomized Phase 2 (C) | ||
|[[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then auto HSCT]] | |[[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then auto HSCT]] | ||
− | |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS24 | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS24<sup>1</sup> |
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for IELSG32 is based on the 2017 update.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *IELSG20: [[#Methotrexate_monotherapy_2|High-dose methotrexate]] x 4 versus [[# | + | *IELSG20: Induction [[#Methotrexate_monotherapy_2|High-dose methotrexate]] x 4 versus [[#Cytarabine_.26_Methotrexate_.28CYM.29|High-dose CYM]] x 4, with any response |
− | *IELSG32: [[#CYM | + | *IELSG32: Induction [[#Cytarabine_.26_Methotrexate_.28CYM.29|CYM]] versus [[#Cytarabine.2C_Methotrexate.2C_Rituximab|Cytarabine, MTX, Rituximab]] versus [[#MATRix|MATRix]] induction, with partial response |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Whole-brain irradiation]] to | + | *[[External_beam_radiotherapy|Whole-brain irradiation]] to 3600 cGy in 1.8000 cGy fractions plus 900 cGy boost to the tumor bed |
− | + | </div></div><br> | |
− | ===Regimen variant #6, | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #6, 4000 cGy + 900 cGy boost {{#subobject:d662c5|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(09)61416-1 Ferreri et al. 2009 (IELSG20)] |
− | |style="background-color:#91cf61"|Non-randomized | + | |2004-2007 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 2 RCT | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Methotrexate_monotherapy_2|High-dose methotrexate]] x 4 versus [[# | + | *Induction [[#Methotrexate_monotherapy_2|High-dose methotrexate]] x 4 versus [[#Cytarabine_.26_Methotrexate_.28CYM.29|High-dose CYM]] x 4, with stable or progressive disease |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Whole-brain irradiation]] to | + | *[[External_beam_radiotherapy|Whole-brain irradiation]] to 4000 cGy in 1.8000 cGy fractions plus 900 cGy boost to the tumor bed |
− | + | </div></div><br> | |
− | ===Regimen variant #7, | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ===Regimen variant #7, 4500 cGy {{#subobject:1475db|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,500: | Line 1,567: | ||
|- | |- | ||
|[https://doi.org/10.1200/JCO.2000.18.17.3144 Abrey et al. 2000] | |[https://doi.org/10.1200/JCO.2000.18.17.3144 Abrey et al. 2000] | ||
− | | | + | |1992-1998 |
|style="background-color:#91cf61"|Non-randomized | |style="background-color:#91cf61"|Non-randomized | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
Line 1,506: | Line 1,573: | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2002.11.013 DeAngelis et al. 2002 (RTOG 93-10)] | |[https://doi.org/10.1200/jco.2002.11.013 DeAngelis et al. 2002 (RTOG 93-10)] | ||
− | |1993 | + | |1993 to not reported |
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
Line 1,513: | Line 1,580: | ||
|[https://doi.org/10.1200/jco.2006.06.2117 Illerhaus et al. 2006] | |[https://doi.org/10.1200/jco.2006.06.2117 Illerhaus et al. 2006] | ||
|1998-2003 | |1998-2003 | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(10)70229-1 Thiel et al. 2010 (G-PCNSL-SG-1)] |
|2000-2009 | |2000-2009 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
|[[CNS_lymphoma_-_null_regimens#Observation|No further treatment]] | |[[CNS_lymphoma_-_null_regimens#Observation|No further treatment]] | ||
− | |style="background-color:# | + | | style="background-color:#ffffbf" |Inconclusive whether non-inferior OS (primary endpoint) |
|- | |- | ||
− | |[https://doi.org/10.1200/jco.2007.12.5062 Shah et al. 2007] | + | |[https://doi.org/10.1200/jco.2007.12.5062 Shah et al. 2007 (MSK 01-146)] |
|2002-2005 | |2002-2005 | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
Line 1,531: | Line 1,598: | ||
|} | |} | ||
''Note that the day count in Illerhaus et al. 2006 starts from the very beginning of treatment.'' | ''Note that the day count in Illerhaus et al. 2006 starts from the very beginning of treatment.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *Abrey et al. 2000 & RTOG 93-10: [[#MPV|MPV]] x 5 | + | *Abrey et al. 2000 & RTOG 93-10: Induction [[#MPV|MPV]] x 5 |
− | *Illerhaus et al. 2006: [[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then autologous hematopoietic stem cell transplant]], with complete response | + | *Illerhaus et al. 2006: [[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then autologous hematopoietic stem cell transplant]] consolidation, with complete response |
− | * | + | *MSK 01-146: Induction [[#R-MPV|R-MPV]] x 5 to 7 cycles, without complete response |
− | *G-PCNSL-SG-1, before 2006: [[#Methotrexate_monotherapy_2|High-dose methotrexate]] x 6 | + | *G-PCNSL-SG-1, before 2006: Induction [[#Methotrexate_monotherapy_2|High-dose methotrexate]] x 6 |
− | *G-PCNSL-SG-1, after 2006: [[#Ifosfamide_.26_Methotrexate|High-dose methotrexate & ifosfamide]] x 6 | + | *G-PCNSL-SG-1, after 2006: Induction [[#Ifosfamide_.26_Methotrexate|High-dose methotrexate & ifosfamide]] x 6 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Whole-brain irradiation]] to | + | *[[External_beam_radiotherapy|Whole-brain irradiation]] to 4500 cGy by the following study-specific criteria: |
− | **Illerhaus et al. 2006: | + | **Illerhaus et al. 2006: 100 cGy fractions, starting on day 90 |
− | **G-PCNSL-SG-1: | + | **G-PCNSL-SG-1: 150 cGy fractions |
− | **Abrey et al. 2000, RTOG 93-10, | + | **Abrey et al. 2000, RTOG 93-10, MSK 01-146: 1.8000 cGy fractions |
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *Abrey et al. 2000 & RTOG 93-10: [[# | + | *Abrey et al. 2000 & RTOG 93-10: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29_2|HiDAC]] consolidation |
− | + | </div></div><br> | |
− | ===Regimen variant #8, | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #8, 5000 cGy {{#subobject:b0e47a|Variant=1}}=== |
+ | {| class="wikitable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2006.06.2117 Illerhaus et al. 2006] | |[https://doi.org/10.1200/jco.2006.06.2117 Illerhaus et al. 2006] | ||
|1998-2003 | |1998-2003 | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|- | |- | ||
|} | |} | ||
''Note that the day count starts from the very beginning of treatment.'' | ''Note that the day count starts from the very beginning of treatment.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then autologous hematopoietic stem cell transplant]], with partial response | + | *[[#BCNU.2FTT.2C_then_auto_HSCT|BCNU/TT, then autologous hematopoietic stem cell transplant]] consolidation, with partial response |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Whole-brain irradiation]] to | + | *[[External_beam_radiotherapy|Whole-brain irradiation]] to 5000 cGy in 100 cGy fractions, starting on day 90 |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol. 2000 Sep;18(17):3144-50. [https://doi.org/10.1200/JCO.2000.18.17.3144 link to original article] ''' | + | # Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol. 2000 Sep;18(17):3144-50. [https://doi.org/10.1200/JCO.2000.18.17.3144 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10963643/ 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. [https://doi.org/10.1200/JCO.2006.06.6910 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17008697 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. [https://doi.org/10.1200/JCO.2006.06.6910 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17008697/ 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. [https://doi.org/10.1200/jco.2002.11.013 link to original article] ''' | + | # '''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. [https://doi.org/10.1200/jco.2002.11.013 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12488408/ PubMed] |
<!-- Presented in part at the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 10-13, 2005. --> | <!-- Presented in part at the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 10-13, 2005. --> | ||
− | # 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. [https://doi.org/10.1200/jco.2006.06.2117 link to original article] ''' | + | # 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. [https://doi.org/10.1200/jco.2006.06.2117 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16864853/ 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. [https://doi.org/10.1093/annonc/mds059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22473593 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. [https://doi.org/10.1093/annonc/mds059 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22473593/ 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. [https:// | + | # 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. [https://doi.org/10.1038/sj.bmt.1705452 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16951691/ 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. [https://doi.org/10.1200/jco.2007.12.5062 link to original article] ''' | + | # 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. [https://doi.org/10.1200/jco.2007.12.5062 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17947720/ PubMed] [https://clinicaltrials.gov/study/NCT00594815 NCT00594815] |
− | + | ## '''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. [https://doi.org/10.1200/jco.2013.50.4910 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5569679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24101038/ 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. [https:// | + | # '''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. [https://doi.org/10.1016/S0140-6736(09)61416-1 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19767089/ PubMed] [https://clinicaltrials.gov/study/NCT00210314 NCT00210314] |
− | # '''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. [https:// | + | # '''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. [https://doi.org/10.1016/S1470-2045(10)70229-1 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20970380/ PubMed] [https://clinicaltrials.gov/study/NCT00153530 NCT00153530] |
− | <!-- ## '''Update: Abstract:''' Agnieszka Korfel, Eckhard Thiel, Peter Martus, Robert Moehle, Frank Griesinger, Michael Rauch, Alexander Roeth, Bernd Hertenstein, Thomas Fischer, Thomas Hundsberger, Hans-Guenther Mergenthaler, Christian Junghanss, Tobias Birnbaum, Lars Fischer, Kristoph Jahnke, Ulrich Herrlinger, Ludwig Plasswilm, Thomas Naegele, Torsten Pietsch, Michael Weller. G-PCNSL-SG-1 randomized phase III trial of high-dose methotrexate with or without whole brain radiotherapy for primary central nervous system lymphoma: Long-term follow-up. J Clin Oncol 32:5s, 2014 (suppl; abstr 8527) [ | + | <!-- ## '''Update: Abstract:''' Agnieszka Korfel, Eckhard Thiel, Peter Martus, Robert Moehle, Frank Griesinger, Michael Rauch, Alexander Roeth, Bernd Hertenstein, Thomas Fischer, Thomas Hundsberger, Hans-Guenther Mergenthaler, Christian Junghanss, Tobias Birnbaum, Lars Fischer, Kristoph Jahnke, Ulrich Herrlinger, Ludwig Plasswilm, Thomas Naegele, Torsten Pietsch, Michael Weller. G-PCNSL-SG-1 randomized phase III trial of high-dose methotrexate with or without whole brain radiotherapy for primary central nervous system lymphoma: Long-term follow-up. J Clin Oncol 32:5s, 2014 (suppl; abstr 8527) [https://doi.org/10.1200/jco.2014.32.15_suppl.8527 link to abstract] --> |
− | ## '''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. [ | + | ## '''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. [https://doi.org/10.1212/wnl.0000000000001395 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25716362/ 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. [ | + | # '''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. [https://doi.org/10.1200/jco.2015.64.8634 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872318/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27022122/ PubMed] [https://clinicaltrials.gov/study/NCT00068250 NCT00068250] |
− | # '''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. [https:// | + | # '''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. [https://doi.org/10.1016/S2352-3026(16)00036-3 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27132696/ PubMed] [https://clinicaltrials.gov/study/NCT01011920 NCT01011920] |
− | + | ## '''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. [https://doi.org/10.1016/S2352-3026(17)30174-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29054815/ PubMed] | |
+ | #'''JCOG1114C:''' Mishima K, Nishikawa R, Narita Y, Mizusawa J, Sumi M, Koga T, Sasaki N, Kinoshita M, Nagane M, Arakawa Y, Yoshimoto K, Shibahara I, Shinojima N, Asano K, Tsurubuchi T, Sasaki H, Asai A, Sasayama T, Momii Y, Sasaki A, Nakamura S, Kojima M, Tamaru JI, Tsuchiya K, Gomyo M, Abe K, Natsumeda M, Yamasaki F, Katayama H, Fukuda H. Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C. Neuro Oncol. 2023 Apr 6;25(4):687-698. [https://doi.org/10.1093/neuonc/noac246 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076938/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36334050/ PubMed] jRCTs031180207 | ||
=Relapsed or refractory, salvage therapy= | =Relapsed or refractory, salvage therapy= | ||
− | + | ==High-dose Cytarabine monotherapy (HiDAC) {{#subobject:c36841|Regimen=1}}== | |
− | ==HiDAC {{#subobject:c36841|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:9c7334|Variant=1}}=== | ===Regimen {{#subobject:9c7334|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable" style="width: 60%; text-align:center;" |
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(10)70229-1 Thiel et al. 2010 (G-PCNSL-SG-1)] |
|2000-2009 | |2000-2009 | ||
− | |style="background-color:#91cf61"|Non-randomized | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | * | + | *G-PCNSL-SG-1, before 2006: Non-response to [[#Methotrexate_monotherapy_2|High-dose methotrexate]] induction |
− | * | + | *G-PCNSL-SG-1, after 2006: Non-response to [[#Ifosfamide_.26_Methotrexate|Methotrexate & Ifosfamide]] induction |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 | *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 | ||
− | |||
'''21-day cycle for 4 cycles''' | '''21-day cycle for 4 cycles''' | ||
− | + | </div></div> | |
===References=== | ===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. [https:// | + | # '''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. [https://doi.org/10.1016/S1470-2045(10)70229-1 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20970380/ PubMed] [https://clinicaltrials.gov/study/NCT00153530 NCT00153530] |
− | <!-- ## '''Update: Abstract:''' Agnieszka Korfel, Eckhard Thiel, Peter Martus, Robert Moehle, Frank Griesinger, Michael Rauch, Alexander Roeth, Bernd Hertenstein, Thomas Fischer, Thomas Hundsberger, Hans-Guenther Mergenthaler, Christian Junghanss, Tobias Birnbaum, Lars Fischer, Kristoph Jahnke, Ulrich Herrlinger, Ludwig Plasswilm, Thomas Naegele, Torsten Pietsch, Michael Weller. G-PCNSL-SG-1 randomized phase III trial of high-dose methotrexate with or without whole brain radiotherapy for primary central nervous system lymphoma: Long-term follow-up. J Clin Oncol 32:5s, 2014 (suppl; abstr 8527) [ | + | <!-- ## '''Update: Abstract:''' Agnieszka Korfel, Eckhard Thiel, Peter Martus, Robert Moehle, Frank Griesinger, Michael Rauch, Alexander Roeth, Bernd Hertenstein, Thomas Fischer, Thomas Hundsberger, Hans-Guenther Mergenthaler, Christian Junghanss, Tobias Birnbaum, Lars Fischer, Kristoph Jahnke, Ulrich Herrlinger, Ludwig Plasswilm, Thomas Naegele, Torsten Pietsch, Michael Weller. G-PCNSL-SG-1 randomized phase III trial of high-dose methotrexate with or without whole brain radiotherapy for primary central nervous system lymphoma: Long-term follow-up. J Clin Oncol 32:5s, 2014 (suppl; abstr 8527) [https://doi.org/10.1200/jco.2014.32.15_suppl.8527 link to abstract] --> |
− | ## '''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. [ | + | ## '''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. [https://doi.org/10.1212/wnl.0000000000001395 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25716362/ PubMed] |
− | + | ==Cytarabine & Etoposide (CYVE) {{#subobject:a2d919|Regimen=1}}== | |
− | ==CYVE {{#subobject:a2d919|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CYVE: '''<u>CY</u>'''tarabine, '''<u>VE</u>'''pesid (Etoposide) | CYVE: '''<u>CY</u>'''tarabine, '''<u>VE</u>'''pesid (Etoposide) | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1 {{#subobject:b4b13a|Variant=1}}=== | ===Regimen variant #1 {{#subobject:b4b13a|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2001.19.3.742 Soussain et al. 2001] |
+ | |1992-1995 | ||
|style="background-color:#91cf61"|Pilot, >20 pts | |style="background-color:#91cf61"|Pilot, >20 pts | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2007.13.5533 Soussain et al. 2008] |
− | |style="background-color:#91cf61"|Phase | + | |2000-2005 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cytarabine (Ara-C)]] | + | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours once per day on days 2 to 5 |
− | + | *[[Cytarabine (Ara-C)]] 50 mg/m<sup>2</sup> IV over 12 hours once per day on days 1 to 5 | |
− | * | ||
*[[Etoposide (Vepesid)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 5 | *[[Etoposide (Vepesid)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 5 | ||
− | |||
'''2 cycles''' | '''2 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *Soussain et al. 2008, responders: [[#Bu.2FTT.2FCy.2C_then_auto_HSCT_2|Bu/TT/Cy, then autologous hematopoietic stem cell transplant]] consolidation |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:921bc8|Variant=1}}=== | ===Regimen variant #2 {{#subobject:921bc8|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1038/sj.bmt.1705452 Colombat et al. 2006] |
− | |style="background-color:#91cf61"|Phase | + | |1999-2001 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *Non-response to [[#MVBP|MVBP]] x 2 | + | *Non-response to [[#MVBP|MVBP]] induction x 2 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2 | *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2 | ||
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV once per day on days 1 & 2 | *[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV once per day on days 1 & 2 | ||
− | |||
'''2 cycles (length not specified)''' | '''2 cycles (length not specified)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Whole_brain_irradiation_2|Whole-brain irradiation]] | + | *[[#Whole_brain_irradiation_2|Whole-brain irradiation]] consolidation |
− | + | </div></div> | |
===References=== | ===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. [ | + | # 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. [https://doi.org/10.1200/jco.2001.19.3.742 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11157026/ 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. [https:// | + | # 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. [https://doi.org/10.1038/sj.bmt.1705452 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16951691/ 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. [ | + | # 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. [https://doi.org/10.1200/jco.2007.13.5533 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18413641/ PubMed] |
− | |||
==Ifosfamide & Methotrexate {{#subobject:683c6d|Regimen=1}}== | ==Ifosfamide & Methotrexate {{#subobject:683c6d|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
*[[Example orders for High-dose Methotrexate (MTX) & Ifosfamide in lymphoma]] | *[[Example orders for High-dose Methotrexate (MTX) & Ifosfamide in lymphoma]] | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:1c70bc|Variant=1}}=== | ===Regimen {{#subobject:1c70bc|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1007/s00277-008-0575-8 Fischer et al. 2008] |
+ | |2002-07 to 2007-08 | ||
|style="background-color:#ffffbe"|Retrospective | |style="background-color:#ffffbe"|Retrospective | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Ifosfamide (Ifex)]] 1500 to 2000 mg/m<sup>2</sup> IV over 3 hours once per day on days 3 to 5 | *[[Ifosfamide (Ifex)]] 1500 to 2000 mg/m<sup>2</sup> IV over 3 hours once per day on days 3 to 5 | ||
*[[Methotrexate (MTX)]] 4000 mg/m<sup>2</sup> IV over 4 hours once on day 1 | *[[Methotrexate (MTX)]] 4000 mg/m<sup>2</sup> IV over 4 hours once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[Mesna (Mesnex)]] for prophylaxis of hemorrhagic cystitis | *[[Mesna (Mesnex)]] for prophylaxis of hemorrhagic cystitis | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] rescue starting 24 hours after start of methotrexate infusion |
− | *Sodium bicarbonate | + | *[[Sodium bicarbonate]] IV or PO 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. | ||
− | + | '''Up to 8 cycles''' (reference did not list timing/criteria to be used for next cycle of therapy) | |
− | [[Methotrexate (MTX)]] dose adjusted for CrCl less than 100 mL/min/1.73m<sup>2</sup> according to the following formula: | + | </div> |
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *[[Methotrexate (MTX)]] dose adjusted for CrCl less than 100 mL/min/1.73m<sup>2</sup> according to the following formula: | ||
*Dose of methotrexate = (CrCl/100) x 4000 mg/m<sup>2</sup>; the paper did not specify what method was used for calculating CrCl. Patients with CrCl less than 50 mL/min/1.73m<sup>2</sup> were excluded from the study. | *Dose of methotrexate = (CrCl/100) x 4000 mg/m<sup>2</sup>; the paper did not specify what method was used for calculating CrCl. Patients with CrCl less than 50 mL/min/1.73m<sup>2</sup> were excluded from the study. | ||
− | + | </div></div> | |
− | |||
− | |||
===References=== | ===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. [ | + | # '''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. [https://doi.org/10.1007/s00277-008-0575-8 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18679681/ PubMed] |
==Whole brain irradiation {{#subobject:49c1e3|Regimen=1}}== | ==Whole brain irradiation {{#subobject:49c1e3|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, 3000 cGy {{#subobject:d82ebe|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1038/sj.bmt.1705452 Colombat et al. 2006] | ||
+ | |1999-2001 | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | ===Regimen variant # | + | ====Preceding treatment==== |
− | {| class="wikitable" style="width: | + | *[[#Cytarabine_.26_Etoposide_.28CYVE.29_2|CYVE]] salvage |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Radiotherapy==== | ||
+ | *[[External_beam_radiotherapy|Whole-brain irradiation]] to 3000 cGy in 180 cGy fractions plus 1000 cGy boost to the tumor bed | ||
+ | '''One course''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 3600 cGy {{#subobject:a2619f|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/jco.2005.01.161 Nguyen et al. 2005] |
− | | | + | |1994-2003 |
− | |style="background-color:#91cf61"| | + | |style="background-color:#91cf61"|Phase 2 |
|- | |- | ||
|} | |} | ||
− | == | + | ''Note: The authors do not clearly describe a pre-determined dosing protocol but report that the most common fraction size was 150 cGy.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Whole-brain irradiation]] to | + | *[[External_beam_radiotherapy|Whole-brain irradiation]]: median dose 3600 cGy (range 28 to 4500 cGy) |
− | + | '''One course''' | |
− | ===Regimen variant # | + | </div></div><br> |
− | {| class="wikitable" style="width: | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | !style="width: | + | ===Regimen variant #3, 3600 cGy + 1000 cGy boost {{#subobject:a2619f|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/jco.2005.01.161 Nguyen et al. 2005] |
− | |style="background-color:#91cf61"|Phase | + | |1994-2003 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | == | + | ''Note: The authors do not clearly describe a pre-determined dosing protocol but report that the most common fraction size was 150 cGy.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Whole-brain irradiation]] to | + | *[[External_beam_radiotherapy|Whole-brain irradiation]]: median dose 3600 cGy (range 19.6 to 4000 cGy) + 1000 cGy (range 10 to 2160 cGy) |
− | + | '''One course''' | |
− | ===Regimen variant # | + | </div></div><br> |
− | {| class="wikitable" style="width: | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | !style="width: | + | ===Regimen variant #4, 4500 cGy {{#subobject:1475db|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable" style="width: 60%; text-align:center;" |
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/S1470-2045(10)70229-1 Thiel et al. 2010 (G-PCNSL-SG-1)] |
− | |style="background-color:#91cf61"| | + | |2000-2009 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | + | ====Preceding treatment==== | |
+ | *G-PCNSL-SG-1, before 2006: Non-response to [[#Methotrexate_monotherapy_2|high-dose MTX]] induction x 6 | ||
+ | *G-PCNSL-SG-1, after 2006: Non-response to [[#Ifosfamide_.26_Methotrexate|High-dose methotrexate & ifosfamide]] induction x 6 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | * | + | *[[External_beam_radiotherapy|Whole-brain irradiation]] to 4500 cGy in 150 cGy fractions |
− | + | '''One course''' | |
− | + | </div></div> | |
− | |||
===References=== | ===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. [ | + | # 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. [https://doi.org/10.1200/jco.2005.01.161 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15735126/ 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. [https:// | + | # 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. [https://doi.org/10.1038/sj.bmt.1705452 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16951691/ 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. [https:// | + | # '''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. [https://doi.org/10.1016/S1470-2045(10)70229-1 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20970380/ PubMed] [https://clinicaltrials.gov/study/NCT00153530 NCT00153530] |
− | <!-- ## '''Update: Abstract:''' Agnieszka Korfel, Eckhard Thiel, Peter Martus, Robert Moehle, Frank Griesinger, Michael Rauch, Alexander Roeth, Bernd Hertenstein, Thomas Fischer, Thomas Hundsberger, Hans-Guenther Mergenthaler, Christian Junghanss, Tobias Birnbaum, Lars Fischer, Kristoph Jahnke, Ulrich Herrlinger, Ludwig Plasswilm, Thomas Naegele, Torsten Pietsch, Michael Weller. G-PCNSL-SG-1 randomized phase III trial of high-dose methotrexate with or without whole brain radiotherapy for primary central nervous system lymphoma: Long-term follow-up. J Clin Oncol 32:5s, 2014 (suppl; abstr 8527) [ | + | <!-- ## '''Update: Abstract:''' Agnieszka Korfel, Eckhard Thiel, Peter Martus, Robert Moehle, Frank Griesinger, Michael Rauch, Alexander Roeth, Bernd Hertenstein, Thomas Fischer, Thomas Hundsberger, Hans-Guenther Mergenthaler, Christian Junghanss, Tobias Birnbaum, Lars Fischer, Kristoph Jahnke, Ulrich Herrlinger, Ludwig Plasswilm, Thomas Naegele, Torsten Pietsch, Michael Weller. G-PCNSL-SG-1 randomized phase III trial of high-dose methotrexate with or without whole brain radiotherapy for primary central nervous system lymphoma: Long-term follow-up. J Clin Oncol 32:5s, 2014 (suppl; abstr 8527) [https://doi.org/10.1200/jco.2014.32.15_suppl.8527 link to abstract] --> |
− | ## '''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. [ | + | ## '''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. [https://doi.org/10.1212/wnl.0000000000001395 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25716362/ PubMed] |
=Consolidation after salvage therapy= | =Consolidation after salvage therapy= | ||
− | |||
==Bu/TT/Cy, then auto HSCT {{#subobject:3f8412|Regimen=1}}== | ==Bu/TT/Cy, then auto HSCT {{#subobject:3f8412|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Bu/TT/Cy: '''<u>Bu</u>'''sulfan, '''<u>T</u>'''hio'''<u>T</u>'''epa, '''<u>Cy</u>'''clophosphamide | Bu/TT/Cy: '''<u>Bu</u>'''sulfan, '''<u>T</u>'''hio'''<u>T</u>'''epa, '''<u>Cy</u>'''clophosphamide | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:ab67a7|Variant=1}}=== | ===Regimen {{#subobject:ab67a7|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2001.19.3.742 Soussain et al. 2001] |
+ | |1992-1995 | ||
|style="background-color:#91cf61"|Pilot, >20 pts | |style="background-color:#91cf61"|Pilot, >20 pts | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2007.13.5533 Soussain et al. 2008] |
− | |style="background-color:#91cf61"|Phase | + | |2000-2005 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *[[#Cytarabine_.26_Etoposide_.28CYVE.29_2|CYVE]] salvage x 2 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Busulfan (Myleran)]] | + | *[[Busulfan (Myleran)]] by the following age-based criteria: |
− | ** | + | **60 years old or younger: 10 mg/kg PO or 8 mg/kg IV once per day on days -6, -5, and -4 |
− | ** | + | **60 years old or older: 6 mg/kg PO or 4.8 mg/kg IV once per day on days -6, -5, and -4 |
*[[Thiotepa (Thioplex)]] 250 mg/m<sup>2</sup> IV once per day on days -9, -8, and -7 | *[[Thiotepa (Thioplex)]] 250 mg/m<sup>2</sup> IV once per day on days -9, -8, and -7 | ||
*[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -3 & -2 | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -3 & -2 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Clonazepam (Klonopin)]] 2 mg/day IV from the first day of busulfan until completion of busulfan |
− | *[[Clonazepam (Klonopin)]] 2 mg/day IV from the first day of | ||
− | |||
'''Stem cell re-infusion occurs on day 0''' | '''Stem cell re-infusion occurs on day 0''' | ||
+ | </div></div> | ||
===References=== | ===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. [ | + | # 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. [https://doi.org/10.1200/jco.2001.19.3.742 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11157026/ 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. [ | + | # 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. [https://doi.org/10.1200/jco.2007.13.5533 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18413641/ PubMed] |
− | |||
=Relapsed or refractory, subsequent lines of therapy= | =Relapsed or refractory, subsequent lines of therapy= | ||
==Rituximab monotherapy {{#subobject:b1f8c5|Regimen=1}}== | ==Rituximab monotherapy {{#subobject:b1f8c5|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:3e2c19|Variant=1}}=== | ===Regimen {{#subobject:3e2c19|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059144/ Batchelor et al. 2011] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059144/ Batchelor et al. 2011 (NABTT-2201)] |
− | |style="background-color:#ffffbe"|Pilot, | + | |2004 to not reported |
+ | |style="background-color:#ffffbe"|Pilot, fewer than 20 pts | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once | + | ====Targeted therapy==== |
− | + | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 | |
− | ''' | + | '''7-day cycle for up to 8 cycles''' |
− | + | </div></div> | |
===References=== | ===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. [ | + | # '''NABTT-2201:''' 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. [https://doi.org/10.1212/wnl.0b013e31820f2d94 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059144/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21383331/ PubMed] [https://clinicaltrials.gov/study/NCT00072449 NCT00072449] |
− | |||
==Temozolomide monotherapy {{#subobject:be70fc|Regimen=1}}== | ==Temozolomide monotherapy {{#subobject:be70fc|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
===Regimen {{#subobject:23777b|Variant=1}}=== | ===Regimen {{#subobject:23777b|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360092/ Reni et al. 2007] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360092/ Reni et al. 2007] | ||
− | |style="background-color:#91cf61"|Phase | + | |2000-2005 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Temozolomide (Temodar)]] 150 mg/m<sup>2</sup> PO once per day on days 1 to 5 | *[[Temozolomide (Temodar)]] 150 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===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. [https:// | + | # 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. [https://doi.org/10.1038/sj.bjc.6603660 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360092/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17325700/ PubMed] |
− | |||
==Temsirolimus monotherapy {{#subobject:021ac0|Regimen=1}}== | ==Temsirolimus monotherapy {{#subobject:021ac0|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
===Regimen {{#subobject:0ad4c0|Variant=1}}=== | ===Regimen {{#subobject:0ad4c0|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2015.64.9897 Korfel et al. 2016 (TemPCNSL)] |
− | |style="background-color:#91cf61"|Phase | + | |2009-2014 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''This is the dose used in stage 2 of this two-stage protocol.'' | + | ''Note: This is the dose used in stage 2 of this two-stage protocol.'' |
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====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 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===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. [ | + | # '''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. [https://doi.org/10.1200/jco.2015.64.9897 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26976424/ PubMed] [https://clinicaltrials.gov/study/NCT00942747 NCT00942747] |
− | |||
==Topotecan monotherapy {{#subobject:f51103|Regimen=1}}== | ==Topotecan monotherapy {{#subobject:f51103|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:26ef01|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1007/s11060-007-9464-6 Voloschin et al. 2008] |
− | | | + | |1998-2002 |
− | + | |style="background-color:#ffffbe"|Phase 2, fewer than 20 pts | |
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
|[https://doi.org/10.1093/annonc/mdl070 Fischer et al. 2006] | |[https://doi.org/10.1093/annonc/mdl070 Fischer et al. 2006] | ||
− | | | + | |2000-2004 |
− | + | |style="background-color:#91cf61"|Phase 2 | |
− | |||
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Topotecan (Hycamtin)]] 1.5 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5 | *[[Topotecan (Hycamtin)]] 1.5 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *Voloschin et al. 2008: [[Ondansetron (Zofran)]] (dose/route not specified) prior to topotecan |
− | *Voloschin et al. 2008: [[Ondansetron (Zofran)]] (dose/route not specified) prior to | ||
− | |||
'''21-day cycle for 6 to 10 cycles''' | '''21-day cycle for 6 to 10 cycles''' | ||
− | + | </div></div> | |
===References=== | ===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. [https://doi.org/10.1093/annonc/mdl070 link to original article] ''' | + | # 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. [https://doi.org/10.1093/annonc/mdl070 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16603598/ 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. [ | + | # 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. [https://doi.org/10.1007/s11060-007-9464-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17896078/ PubMed] |
− | |||
=Prognosis= | =Prognosis= | ||
− | |||
==IELSG Prognostic Scoring System (2003)== | ==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. [ | + | # 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. [https://doi.org/10.1200/jco.2003.09.139 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12525518/ PubMed] |
− | |||
[[Category:CNS lymphoma regimens]] | [[Category:CNS lymphoma regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:CNS cancers]] | [[Category:CNS cancers]] |
Latest revision as of 17:13, 17 July 2024
Section editor | Section editor | ||
---|---|---|---|
Seema Nagpal, MD Stanford University Palo Alto, CA, USA |
Tarsheen Sethi, MD, MSCI Yale University New Haven, CT, USA |
Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
42 regimens on this page
60 variants on this page
|
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
BSH
- 2018: Fox et al. Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma PubMed
EANO
- 2015: Hoang-Xuan et al. Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology PubMed
EHA/ESMO
- 2024: Ferreri et al. Primary central nervous system lymphomas: EHA-ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up PubMed
ESH
- 2019: Fox et al. Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma PubMed
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) PubMed
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Central Nervous System Cancers.
CNS prophylaxis, systemic therapy
High-dose Cytarabine monotherapy (HiDAC)
HiDAC: High Dose Ara-C (Cytarabine)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Holte et al. 2013 (NLG LBC-04) | 2004-2008 | Phase 2 |
Note: IT treatment was not part of prophylaxis, except that Methotrexate (MTX) 15 mg IT was allowed at time of diagnostic LP.
Preceding treatment
- Induction R-CHOEP-14 x 8
Chemotherapy
- Cytarabine (Ara-C) by the following age-based criteria:
- Younger than 60 years old: 3000 mg/m2 IV twice per day on days 1 & 2 (total dose: 12,000 mg/m2)
- 60 to 65 years old: 2000 mg/m2 IV twice per day on days 1 & 2 (total dose: 8000 mg/m2)
- Older than 65 years old: not defined
21-day course
Subsequent treatment
- Induction HD-MTX
References
- NLG LBC-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 dosing details in manuscript have been reviewed by our editors PubMed NCT01502982
Methotrexate monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Holte et al. 2013 (NLG LBC-04) | 2004-2008 | Phase 2 |
Note: IT treatment was not part of prophylaxis, except that Methotrexate (MTX) 15 mg IT was allowed at time of diagnostic LP.
Preceding treatment
- Induction HiDAC
Chemotherapy
- Methotrexate (MTX) 3000 mg/m2 IV continuous infusion over 24 hours, started on day 1
Supportive therapy
- Leucovorin (Folinic acid) (dose/frequency not specified) starting at 36 hours
One course
References
- NLG LBC-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 dosing details in manuscript have been reviewed by our editors PubMed NCT01502982
CNS treatment, local therapy
IT Cytarabine monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Glantz et al. 1999 | 1994-1998 | Phase 3 (C) | IT liposomal cytarabine | Inferior ORR |
CNS therapy, treatment
- Cytarabine (Ara-C) 50 mg IT once per day on days 1, 4, 8, 11, 15, 18, 22, 25
4-week course
Subsequent treatment
- Glantz et al. 1999, responders: 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 dosing details in manuscript have been reviewed by our editors PubMed
IT Cytarabine liposomal monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Glantz et al. 1999 | 1994-1998 | Phase 3 (E-RT-switch-ic) | IT cytarabine | Superior ORR (secondary endpoint) |
Note: this study was not designed to make formal statitiscal comparisons, but the difference in ORR was very large.
CNS therapy, treatment
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 1
14-day cycle for 2 cycles
Subsequent treatment
- Glantz et al. 1999, responders: 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 dosing details in manuscript have been reviewed by our editors PubMed
Upfront therapy, randomized data
Cytarabine & Methotrexate (CYM)
CYM: CYtarabine & Methotrexate
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ferreri et al. 2009 (IELSG20) | 2004-2007 | Randomized Phase 2, >20 per arm (E-esc) | High-dose MTX | Seems to have superior CR rate (primary endpoint) |
Ferreri et al. 2016 (IELSG32) | 2010-2014 | Randomized Phase 2 (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 therapy
- 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, with 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 consolidation , within 4 weeks
- IELSG32: Whole brain irradiation versus Carmustine & Thiotepa with auto HSCT consolidation
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 dosing details in manuscript have been reviewed by our editors PubMed NCT00210314
- 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 dosing details in manuscript have been reviewed by our editors PubMed NCT01011920
Cytarabine, Methotrexate, Rituximab
R-HD-MTX/ARA-C: Rituximab, High-Dose MethoTreXate, ARA-C (Cytarabine)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ferreri et al. 2015 (SCNSL1) | 2006-2013 | Phase 2 | ||
Ferreri et al. 2016 (IELSG32) | 2010-2014 | Randomized Phase 2 (E-esc) | 1. CYM | 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: Induction 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 therapy
- Levoleucovorin (Fusilev) 15 mg/m2 IV every 6 hours for 12 doses, beginning 24 hours after the start of methotrexate, with 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)
- IELSG32: Whole brain irradiation versus Carmustine & Thiotepa with auto HSCT consolidation
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 NCT00801216
- 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 dosing details in manuscript have been reviewed by our editors PubMed NCT01011920
MATRix
MATRix: Methotrexate, Ara-C (Cytarabine), Thiotepa, Rituximab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ferreri et al. 2016 (IELSG32) | 2010-2014 | Randomized Phase 2 (E-esc) | 1. CYM | Superior CR rate (primary endpoint) |
2. Cytarabine, Methotrexate, Rituximab | Seems to have superior CR rate (primary endpoint) |
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 therapy
- Levoleucovorin (Fusilev) 15 mg/m2 IV every 6 hours for 12 doses, beginning 24 hours after the start of methotrexate, with 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
- Whole brain irradiation versus Carmustine & Thiotepa with auto HSCT consolidation
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 dosing details in manuscript have been reviewed by our editors PubMed NCT01011920
MBVP
MBVP: Methotrexate, BCNU (Carmustine), Vumon (Teniposide), Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bromberg et al. 2019 (HOVON 105/ALLG NHL 24) | 2010-2016 | Phase 3 (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
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
28-day cycle for 2 cycles
Subsequent treatment
- HOVON 105/ALLG NHL 24, responders 60 years old or older: HiDAC consolidation
- HOVON 105/ALLG NHL 24, responders younger than 60: HiDAC consolidation, then low-dose WBRT consolidation
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 dosing details in abstract have been reviewed by our editors PubMed ACTRN12610000908033
- HRQoL analysis: van der Meulen M, Bakunina K, Nijland M, Minnema MC, Cull G, Stevens WBC, Baars JW, Mason KD, Beeker A, Beijert M, Taphoorn MJB, van den Bent MJ, Issa S, Doorduijn JK, Bromberg JEC, Dirven L. Health-related quality of life after chemotherapy with or without rituximab in primary central nervous system lymphoma patients: results from a randomised phase III study. Ann Oncol. 2020 Aug;31(8):1046-1055. Epub 2020 May 3. link to original article PubMed
Methotrexate monotherapy
Regimen variant #1, 3500 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ferreri et al. 2009 (IELSG20) | 2004-2007 | Randomized Phase 2 (C) | CYM; high-dose | 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 consolidation, within 4 weeks
Regimen variant #2, 4000 mg/m2
Study | Dates of enrollment | Evidence |
---|---|---|
Thiel et al. 2010 (G-PCNSL-SG-1) | 2000-2009 | Non-randomized part of phase 3 RCT |
Note: All patients received the same induction regimen; however, the induction regimen was changed after 2006 to high-dose MTX & ifosfamide.
Subsequent treatment
- G-PCNSL-SG-1, patients with CR: whole-brain irradiation consolidation versus no further treatment
- G-PCNSL-SG-1, patients with less than CR in the WB-XRT arm: Salvage whole-brain irradiation
- G-PCNSL-SG-1, patients with less than CR in the no-WB-XRT: Salvage HiDAC
Regimen variant #3, 8000 mg/m2
Study | Dates of enrollment | Evidence |
---|---|---|
Herrlinger et al. 2005 (NOA-03) | 1998-05 to 2000-03 | Phase 2 |
Note: This was considered a negative trial by the authors and is included here for historical purposes.
Subsequent treatment
- NOA-03, 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 | Dates of enrollment | Evidence |
---|---|---|
Batchelor et al. 2003 (NABTT 96-07) | 1998-1999 | Phase 2 |
Chemotherapy
- Methotrexate (MTX) by the following renal function-based criteria:
- CrCl 100 mL/min/1.73m2 or more: 8000 mg/m2 IV over 4 hours once on day 1
- 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 to 4000 mg/m2.
14-day cycle until CR or a maximum of 8 cycles
Subsequent treatment
- NABTT 96-07, patients achieving CR: HD-MTX continuation x 2, then methotrexate maintenance
Regimen variant #5, 20-day course
Study | Dates of enrollment | Evidence |
---|---|---|
Montemurro et al. 2007 (OSHO-53) | 1999-2004 | Phase 2 |
Chemotherapy
- Methotrexate (MTX) by the following age-based criteria:
- 60 years old or younger: 8000 mg/m2 IV over 4 hours once per day on days 1 & 10
- Older than 60 years old: 6000 mg/m2 IV over 4 hours once per day on days 1 & 10
20-day course
Subsequent treatment
- OSHO-53, responders (CR or PR): Bu/TT, then autologous HSCT consolidation
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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00210314
- 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00153530
- 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
MCP: Methotrexate, CCNU (Lomustine), Procarbazine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Illerhaus et al. 2008a | 1998-2004 | Phase 2 |
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 therapy
- Leucovorin (Folinic acid) 15 mg/m2 (route not specified) every 6 hours beginning 24 hours after start of methotrexate 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 dosing details in manuscript have been reviewed by our editors PubMed
Lomustine, Methotrexate, Procarbazine, Methylprednisolone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Hoang-Xuan et al. 2003 (EORTC 26952) | 1997-1999 | Phase 2 |
Note: This was the first prospective phase 2 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
Glucocorticoid therapy
- 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
CNS therapy
- Methotrexate (MTX) 15 mg IT (admixed with cytarabine) once per day on days 1, 5, 10, 15
- Cytarabine (Ara-C) 40 mg IT (admixed with methotrexate) once per day on days 1, 5, 10, 15
Supportive therapy
- Leucovorin (Folinic acid) 25 mg PO every 6 hours for 3 days, initiated 24 hours after IV methotrexate administrations, and 10 mg PO every 6 hours for 2 days after IT methotrexate administrations
45-day course
Subsequent treatment
- EORTC 26952, 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 dosing details in manuscript have been reviewed by our editors PubMed
MATRix-RICE
MATRix-RICE: Methotrexate, Ara-C (Cytarabine), Thiotepa, Rituximab, followed by Rituximab,
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Ferreri et al. 2021 (MARIETTA) | 2015-03-30 to 2018-08-03 | Phase 2 |
Chemotherapy, MATRix portion (cycles 1 to 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)
- 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, MATRix portion (cycles 1 to 3)
- Rituximab (Rituxan) 375 mg/m2 IV once on day 0
CNS therapy, MATRix portion (cycles 1 to 3)
- ONE of the following:
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 5
- Triple therapy with Methotrexate (MTX) 12 mg; Cytarabine (Ara-C) 50 mg; Hydrocortisone (Cortef) 50 mg IT once on day 5
Targeted therapy, RICE portion (cycles 4 to 6)
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy, RICE portion (cycles 4 to 6)
- Ifosfamide (Ifex) 5000 mg/m2 IV continuous infusion over 24 hours, started on day 2
- Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 2
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 3
CNS therapy, RICE portion (cycles 4 to 6)
- ONE of the following:
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 4
- Triple therapy with Methotrexate (MTX) 12 mg; Cytarabine (Ara-C) 50 mg; Hydrocortisone (Cortef) 50 mg IT once on day 4
Supportive therapy, RICE portion (cycles 4 to 6)
21-day cycle for 6 cycles
Subsequent treatment
- Carmustine & Thiotepa with auto HSCT consolidation
References
- MARIETTA: Ferreri AJM, Doorduijn JK, Re A, Cabras MG, Smith J, Ilariucci F, Luppi M, Calimeri T, Cattaneo C, Khwaja J, Botto B, Cellini C, Nassi L, Linton K, McKay P, Olivieri J, Patti C, Re F, Fanni A, Singh V, Bromberg JEC, Cozens K, Gastaldi E, Bernardi M, Cascavilla N, Davies A, Fox CP, Frezzato M, Osborne W, Liberati AM, Novak U, Zambello R, Zucca E, Cwynarski K; International Extranodal Lymphoma Study Group (IELSG). MATRix-RICE therapy and autologous haematopoietic stem-cell transplantation in diffuse large B-cell lymphoma with secondary CNS involvement (MARIETTA): an international, single-arm, phase 2 trial. Lancet Haematol. 2021 Feb;8(2):e110-e121. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02329080
Methotrexate-Cytarabine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Abrey et al. 2003 | Not reported | Phase 2 |
Note: Patients proceed to part two 72 hours after 5th dose of MTX or once the 5th dose MTX level has cleared.
Chemotherapy, first portion (cycles 1 to 5)
- Methotrexate (MTX) 3500 mg/m2 (maximum dose of 7000 mg) IV over 2 hours once on day 1
Supportive therapy, first portion (cycles 1 to 5)
- Leucovorin (Folinic acid) 25 mg PO every 6 hours, beginning 24 hours after start of methotrexate, continued for 12 doses or until serum MTX level less than 100 nmol/L
Chemotherapy, second portion (cycles 6 & 7)
- Cytarabine (Ara-C) 3000 mg/m2 IV once per day on days 1 & 2
Supportive therapy, second portion
- Filgrastim (Neupogen) as follows:
- Cycle 6: 10 mcg/kg SC once per day, starting on day 4 and continued until stem cell collection complete
- Cycle 7: 5 mcg/kg SC once per day continued for 2 weeks or until ANC greater than 3000/μL
14-day cycle for 5 cycles, then 1-month cycle for 2 cycles (stem cell collection took place between cycles 6 & 7)
Subsequent treatment
- BEAM, then autologous hematopoietic stem cell transplant consolidation
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 dosing details in manuscript have been reviewed by our editors PubMed
Methotrexate-Cytarabine & Thiotepa
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Illerhaus et al. 2006 | 1998-2003 | Phase 2 |
Chemotherapy, MTX portion (course 1)
- Methotrexate (MTX) 8000 mg/m2 IV over 4 hours once per day on days 1, 10, 20
Supportive therapy, MTX portion (course 1)
- Leucovorin (Folinic acid) 15 mg/m2 every 6 hours, beginning 24 hours after start of methotrexate, continuing until clearance
Patients with CR, PR, or SD "with clinical improvement" after the 2nd dose of MTX proceeded to:
Chemotherapy, stem cell mobilization portion (course 2)
- Cytarabine (Ara-C) 3000 mg/m2 IV over 3 hours once per day on days 2 & 3
- Thiotepa (Thioplex) 40 mg/m2 (route not specified) once on day 3
28-day course, then 20-day course
Subsequent treatment
Protocol variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Illerhaus et al. 2008 | 2003-2006 | Pilot, fewer than 20 patients |
Chemotherapy, part 1
- Methotrexate (MTX) 8000 mg/m2 IV over 4 hours once on day 1
Supportive therapy
- Leucovorin (Folinic acid) 15 mg/m2 every 6 hours, beginning 24 hours after start of methotrexate, 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Chamberlain et al. 2010 | 2000-2007 | Phase 2 |
Note: the bounds as described in the paper do not account for the situation where CrCl = 60 mL/min/1.73m2.
Chemotherapy
- Methotrexate (MTX) by the following renal function-based criteria:
- CrCl more 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
- Chamberlain et al. 2010, 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. Epub 2010 Feb 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
MPV
MPV: Methotrexate, Procarbazine, Vincristine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Abrey et al. 2000 | 1992-1998 | Non-randomized |
DeAngelis et al. 2002 (RTOG 93-10) | 1993 to not reported | Phase 2 |
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
CNS therapy
- Methotrexate (MTX) 12 mg IT once on day 8 (via Ommaya reservoir)
Supportive therapy
- Leucovorin (Folinic acid) as follows:
- Days 2 to 4: 20 mg PO every 6 hours for 12 doses, beginning 24 hours after IV methotrexate administration
- Days 8 & 9: 10 mg PO every 6 hours for 8 doses, beginning on the evening of IT methotrexate 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
- Whole-brain irradiation consolidation
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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors PubMed
MT-R
MT-R: Methotrexate, Temozolomide, Rituximab
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Glass et al. 2016 (RTOG 0227) | Not reported | Phase 1/2 |
Note: This is the MTD of this phase 1/2 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
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once, 3 days prior to first dose of MTX
Supportive therapy
- Leucovorin (Folinic acid) 25 mg IV every 6 hours, starting 24 hours after methotrexate, continue until MTX level less than 100 nmol/L
14-day cycle for 5 cycles
Subsequent treatment
- WB-XRT consolidation
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Rubenstein et al. 2013 (CALGB 50202) | 2004-2009 | Phase 2 |
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
Targeted therapy
- Rituximab (Rituxan) as follows:
- Cycles 1 to 6: 375 mg/m2 IV once on day 3
Supportive therapy
- Leucovorin (Folinic acid) 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
- CALGB 50202, patients achieving CR or CRu: CYVE consolidation
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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00098774
- 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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00068250
MVBP
MVBP: Methotrexate, VP16 (Etoposide), BCNU (Carmustine), MethylPrednisolone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Colombat et al. 2006 | 1999-2001 | Phase 2 |
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
Glucocorticoid therapy
- Methylprednisolone (Solumedrol) 60 mg/m2 (route not specified) once per day on days 1 to 5
Supportive therapy
- Leucovorin (Folinic acid) details not specified
2 courses (length not specified), separated by 21 days
CNS therapy
- Methotrexate (MTX) 20 mg IT (admixed with cytarabine and methylpredinsolone)
- Cytarabine (Ara-C) 50 mg IT (admixed with methotrexate and methylprednisolone)
- Methylprednisolone (Solumedrol) 40 mg IT (admixed with cytarabine and methotrexate)
6 doses total (timing not specified)
Subsequent treatment
- Colombat et al. 2006, responding patients (CR or PR): Cytarabine & Ifosfamide for stem cell mobilization, then BEAM, then autologous hematopoietic stem cell transplant consolidation
- Colombat et al. 2006, 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 dosing details in manuscript have been reviewed by our editors PubMed
Nordic Regimen, older patients
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Pulczynski et al. 2015 (NLGPCNSL) | 2007-2010 | Phase 2 |
Eligibility criteria
- Age 66-75 years
Targeted therapy, A portion
- Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m2 IV once on day 1
Chemotherapy, A portion
- Methotrexate (MTX) as follows:
- Cycles 1 & 4: 3000 mg/m2 IV once on day 1
- Ifosfamide (Ifex) as follows:
- Cycle 1: 800 mg/m2 IV once per day on days 2 to 5
Glucocorticoid therapy, A portion (cycles 1 & 4)
- Dexamethasone (Decadron) 10 mg/m2/day PO on days 2 to 5
CNS therapy, A portion (cycles 1 & 4)
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 2
Chemotherapy, B portion (cycles 2 & 5)
- Methotrexate (MTX) 5000 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 150 mg/m2 IV once per day on days 2 to 6
Glucocorticoid therapy, B portion (cycles 2 & 5)
- Dexamethasone (Decadron) 10 mg/m2/day PO on days 2 to 5
CNS therapy, B portion (cycles 2 & 5)
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 2
Glucocorticoid therapy, C portion (cycles 3 & 6)
- Dexamethasone (Decadron) 20 mg/m2/day PO on days 3 to 7
Chemotherapy, C portion (cycles 3 & 6)
- 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
- Temozolomide maintenance
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 dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01458730
Nordic Regimen, younger patients
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Pulczynski et al. 2015 (NLGPCNSL) | 2007-2010 | Phase 2 |
Eligibility criteria
- Age: 18 to 65 years
Targeted therapy, A portion (cycles 1 & 4)
- Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m2 IV once on day 1
Chemotherapy, A portion (cycles 1 & 4)
- Methotrexate (MTX) 5000 mg/m2 IV once on day 1
- Ifosfamide (Ifex) 800 mg/m2 IV once per day on days 2 to 5
Glucocorticoid therapy, A portion (cycles 1 & 4)
- Dexamethasone (Decadron) 10 mg/m2/day PO on days 2 to 5
CNS therapy, A portion (cycles 1 & 4)
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 2
Chemotherapy, B portion (cycles 2 & 5)
- Methotrexate (MTX) 5000 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
- Cyclophosphamide (Cytoxan) 200 mg/m2 IV once per day on days 2 to 5
Glucocorticoid therapy, B portion (cycles 2 & 5)
- Dexamethasone (Decadron) 10 mg/m2/day PO on days 2 to 5
CNS therapy, B portion (cycles 2 & 5)
- Cytarabine liposomal (DepoCyt) 50 mg IT once on day 2
Glucocorticoid therapy, C portion (cycles 3 & 6)
- Dexamethasone (Decadron) 20 mg/m2/day PO on days 3 to 7
Chemotherapy, C portion (cycles 3 & 6)
- 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 dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01458730
R-MCP (CCNU)
R-MCP: Rituximab, Methotrexate, CCNU (Lomustine), Procarbazine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Fritsch et al. 2011 | 2005-2009 | Phase 2 |
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 therapy
- Leucovorin (Folinic acid) (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 dosing details in manuscript have been reviewed by our editors PubMed
R-MP
R-MP: Rituximab, Methotrexate, Procarbazine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Fritsch et al. 2016 (PRIMAIN) | 2009-2013 | Phase 2 |
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 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
- Procarbazine maintenance
References
- PRIMAIN: 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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00989352
- PRIMA-CNS: DRKS00024085
R-MPV
R-MPV: Rituximab, Methotrexate, Procarbazine, Vincristine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Shah et al. 2007 (MSK 01-146) | 2002-2005 | Phase 2 |
Omuro et al. 2015 (MSK 04-129) | 2005-2011 | Phase 2 |
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
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2.8 mg) IV once on day 2
CNS therapy
- (only described in MSK 01-146)
- Methotrexate (MTX) 12 mg IT (via Ommaya) once sometime between day 5 and 12 (for patients with positive CSF cytology)
Supportive therapy
- Leucovorin (Folinic acid) 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 administration
14-day cycle for 5 to 7 cycles
Subsequent treatment
- MSK 01-146: whole-brain irradiation consolidation, in 3 to 5 weeks
- MSK 04-129: Bu/TT/Cy, then autologous hematopoietic stem cell transplant consolidation, after 5 cycles if CR achieved, or after 7 cycles for PR/CR at that time
References
- MSK 01-146: 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00594815
- 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 link to PMC 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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00596154
Consolidation after upfront therapy
BCNU/TT, then auto HSCT
BCNU/TT: BCNU (Carmustine), ThioTepa
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Illerhaus et al. 2006 | 1998-2003 | Phase 2 |
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 therapy
- Autologous stem cells re-infused on day 56
- 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."
One course
Subsequent treatment
- Whole-brain irradiation consolidation
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Illerhaus et al. 2008 | 2003-2006 | Pilot, fewer than 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
Supportive therapy
- Autologous stem cells re-infused on day 7
One course
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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors PubMed NCT01011920
- 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
BEAM: BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Colombat et al. 2006 | 1999-2001 | Phase 2 |
Preceding treatment
- MVBP induction 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 (total dose: 800 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once on day 6
Supportive therapy
- Autologous stem cells re-infused on unspecified day
One course
Subsequent treatment
- Whole-brain irradiation consolidation
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Abrey et al. 2003 | Not reported | Phase 2 |
Preceding treatment
- Methotrexate, then Cytarabine induction
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 100 mg/m2 IV every 12 hours on days -5 to -2 (total dose: 800 mg/m2)
- Cytarabine (Ara-C) 200 mg/m2 IV every 12 hours on days -5 to -2 (total dose: 1600 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive therapy
- Autologous stem cells re-infused on day 0
- (described in some publications)
- Filgrastim (Neupogen) by the following weight-based criteria:
- Less than 70 kg: 300 mcg SC once per day, starting on day +7 after stem cell transplant
- More than 70 kg (reference did not clarify which dosage to use for patients who are exactly 70 kg): 480 mcg SC once per day, starting on day +7 after stem cell transplant
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day on Monday and Thursdays, until 6 months after BEAM
- Ciprofloxacin (Cipro) 500 mg PO twice per day while ANC less than 500/μL
- Antifungal prophylaxis with one of the following:
- Fluconazole (Diflucan) 100 mg PO once per day while ANC less than 500/μL
- Nystatin (Mycostatin) 500,000 units swish & swallow four times per day while ANC less than 500/μL
- Acyclovir (Zovirax) 400 mg PO three times per day while ANC less than 500/μL
One course
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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors PubMed
Bu/TT, then auto HSCT
Bu/TT: Busulfan, ThioTepa
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Montemurro et al. 2007 (OSHO-53) | 1999-2004 | Phase 2 |
Preceding treatment
- High-dose methotrexate induction x 2
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
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
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 dosing details in manuscript have been reviewed by our editors PubMed
Bu/TT/Cy, then auto HSCT
Bu/TT/Cy: Busulfan, ThioTepa, Cyclophosphamide
TBC: Thiotepa, Busulfan, Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Omuro et al. 2015 (MSK 04-129) | 2005-2011 | Phase 2 |
Preceding treatment
- R-MPV induction
Chemotherapy
- Thiotepa (Thioplex) 250 mg/m2 IV once per day on days -9, -8, and -7
- Busulfan (Myleran) 3.2 mg/kg IV once per day on days -6, -5, and -4
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 and -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00596154
High-dose Cytarabine monotherapy (HiDAC)
HiDAC: High Dose Ara-C (Cytarabine)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Abrey et al. 2000 | 1992-1998 | Non-randomized |
DeAngelis et al. 2002 (RTOG 93-10) | 1993 to not reported | Phase 2 |
Time interval of cycles is not explicitly described and is derived from Table 1 in DeAngelis et al. 2002.
Preceding treatment
- Definitive Whole-brain irradiation x 4500 cGy
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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors PubMed
Cytarabine & Etoposide (CYVE)
CYVE: CYtarabine & VEpesid (Etoposide)
EA: Etoposide & Ara-C (Cytarabine)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Rubenstein et al. 2013 (CALGB 50202) | 2004-2009 | Phase 2 |
Preceding treatment
- MT-R induction
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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00098774
Lomustine, Methotrexate, Procarbazine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Hoang-Xuan et al. 2003 (EORTC 26952) | 1997-1999 | Phase 2 |
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
CNS therapy
- Methotrexate (MTX) 15 mg IT (admixed with cytarabine) once on day 1
- Cytarabine (Ara-C) 40 mg IT (admixed with methotrexate) once on day 1
Supportive therapy
- Leucovorin (Folinic acid) 25 mg PO every 6 hours for 3 days, initiated 24 hours after IV methotrexate 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 dosing details in manuscript have been reviewed by our editors PubMed
Methotrexate monotherapy
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Chamberlain et al. 2010 | 2000-2007 | Phase 2 |
Note: the bounds as described in the paper do not account for the situation where CrCl = 60 mL/min/1.73m2.
Preceding treatment
- High-dose methotrexate & Rituximab induction
Chemotherapy
- Methotrexate (MTX) by the following renal function-based criteria:
- CrCl more 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 | Dates of enrollment | Evidence |
---|---|---|
Batchelor et al. 2003 (NABTT 96-07) | 1998-1999 | Phase 2 |
Preceding treatment
- High-dose methotrexate induction
Chemotherapy
- Methotrexate (MTX) by the following renal function-based criteria:
- CrCl 100 mL/min/1.73m2 or more: 8000 mg/m2 IV over 4 hours once on day 1
- 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 to 4000 mg/m2.
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 dosing details in manuscript have been reviewed by our editors 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. Epub 2010 Feb 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
Procarbazine monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Fritsch et al. 2016 (PRIMAIN) | 2009-2013 | Phase 2 |
Preceding treatment
- Induction 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
- PRIMAIN: 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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00989352
Temozolomide monotherapy
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Glass et al. 2016 (RTOG 0227) | Not reported | Phase 1/2 |
Preceding treatment
- WB-XRT consolidation
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
50-week course
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Pulczynski et al. 2015 (NLGPCNSL) | 2007-2010 | Phase 2 |
Preceding treatment
- Nordic Regimen for older patients induction
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 dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01458730
- 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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00068250
Whole brain irradiation
WBRT: Whole-Brain Radiation Therapy
Regimen variant #1, 2340 cGy
Study | Dates of enrollment | Evidence |
---|---|---|
Shah et al. 2007 (MSK 01-146) | 2002-2005 | Phase 2 |
Preceding treatment
- Induction R-MPV x 5 to 7 cycles, with complete response
Radiotherapy
- Whole-brain irradiation to 2340 cGy in 1.8000 cGy fractions
Regimen variant #2, 3000 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Colombat et al. 2006 | 1999-2001 | Phase 2 | ||
Mishima et al. 2023 (JCOG1114C) | 2014-09-20 to 2018-08-24 | Phase 3 (C) | Temozolomide & WBRT | Might have superior OS OS24: 86.8% vs 71.4% (HR 0.46, 95% CI 0.20-1.05) |
Preceding treatment
- Colombat et al. 2006: BEAM, then autologous hematopoietic stem cell transplant consolidation, with complete response
- JCOG1114C: HD-MTX induction
Radiotherapy
- Whole-brain irradiation to 3000 cGy in 1.8000 cGy fractions
Regimen variant #3, 3000 cGy + 1000 cGy boost
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Colombat et al. 2006 | 1999-2001 | Phase 2 | ||
Mishima et al. 2023 (JCOG1114C) | 2014-09-20 to 2018-08-24 | Phase 3 (C) | Temozolomide & WBRT | Might have superior OS OS24: 86.8% vs 71.4% (HR 0.46, 95% CI 0.20-1.05) |
Note: boost was optional in JCOG1114C.
Preceding treatment
- Colombat et al. 2006: BEAM, then autologous hematopoietic stem cell transplant consolidation, with partial response
- JCOG1114C: HD-MTX induction
Radiotherapy
- Whole-brain irradiation to 3000 cGy in 1.8000 cGy fractions plus 1000 cGy boost to the tumor bed
Regimen variant #4, 3600 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Glass et al. 2016 (RTOG 0227) | Not reported | Phase 1/2 | ||
Ferreri et al. 2016 (IELSG32) | 2010-2014 | Randomized Phase 2 (C) | BCNU/TT, then auto HSCT | Did not meet primary endpoint of PFS241 |
1Reported efficacy for IELSG32 is based on the 2017 update.
Preceding treatment
- RTOG 0227: MT-R induction
- IELSG32: CYM versus Cytarabine, MTX, Rituximab versus MATRix induction, with complete response
Radiotherapy
- Whole-brain irradiation to 3600 cGy by the following study-specific criteria:
- RTOG 0227: 120 cGy twice per day fractions on weeks 11 to 13
- IELSG32: 1.8000 cGy fractions
Subsequent treatment
- RTOG 0227: Temozolomide consolidation
Regimen variant #5, 3600 cGy + 900 cGy boost
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ferreri et al. 2009 (IELSG20) | 2004-2007 | Non-randomized part of phase 2 RCT | ||
Ferreri et al. 2016 (IELSG32) | 2010-2014 | Randomized Phase 2 (C) | BCNU/TT, then auto HSCT | Did not meet primary endpoint of PFS241 |
1Reported efficacy for IELSG32 is based on the 2017 update.
Preceding treatment
- IELSG20: Induction High-dose methotrexate x 4 versus High-dose CYM x 4, with any response
- IELSG32: Induction CYM versus Cytarabine, MTX, Rituximab versus MATRix induction, with partial response
Radiotherapy
- Whole-brain irradiation to 3600 cGy in 1.8000 cGy fractions plus 900 cGy boost to the tumor bed
Regimen variant #6, 4000 cGy + 900 cGy boost
Study | Dates of enrollment | Evidence |
---|---|---|
Ferreri et al. 2009 (IELSG20) | 2004-2007 | Non-randomized part of phase 2 RCT |
Preceding treatment
- Induction High-dose methotrexate x 4 versus High-dose CYM x 4, with stable or progressive disease
Radiotherapy
- Whole-brain irradiation to 4000 cGy in 1.8000 cGy fractions plus 900 cGy boost to the tumor bed
Regimen variant #7, 4500 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Abrey et al. 2000 | 1992-1998 | Non-randomized | ||
DeAngelis et al. 2002 (RTOG 93-10) | 1993 to not reported | Phase 2 | ||
Illerhaus et al. 2006 | 1998-2003 | Phase 2 | ||
Thiel et al. 2010 (G-PCNSL-SG-1) | 2000-2009 | Phase 3 (E-esc) | No further treatment | Inconclusive whether non-inferior OS (primary endpoint) |
Shah et al. 2007 (MSK 01-146) | 2002-2005 | Phase 2 |
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: Induction MPV x 5
- Illerhaus et al. 2006: BCNU/TT, then autologous hematopoietic stem cell transplant consolidation, with complete response
- MSK 01-146: Induction R-MPV x 5 to 7 cycles, without complete response
- G-PCNSL-SG-1, before 2006: Induction High-dose methotrexate x 6
- G-PCNSL-SG-1, after 2006: Induction High-dose methotrexate & ifosfamide x 6
Radiotherapy
- Whole-brain irradiation to 4500 cGy by the following study-specific criteria:
- Illerhaus et al. 2006: 100 cGy fractions, starting on day 90
- G-PCNSL-SG-1: 150 cGy fractions
- Abrey et al. 2000, RTOG 93-10, MSK 01-146: 1.8000 cGy fractions
Subsequent treatment
- Abrey et al. 2000 & RTOG 93-10: HiDAC consolidation
Regimen variant #8, 5000 cGy
Study | Dates of enrollment | Evidence |
---|---|---|
Illerhaus et al. 2006 | 1998-2003 | Phase 2 |
Note that the day count starts from the very beginning of treatment.
Preceding treatment
- BCNU/TT, then autologous hematopoietic stem cell transplant consolidation, with partial response
Radiotherapy
- Whole-brain irradiation to 5000 cGy in 100 cGy 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00594815
- 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 link to PMC 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00210314
- 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00153530
- 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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00068250
- 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 dosing details in manuscript have been reviewed by our editors PubMed NCT01011920
- 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
- JCOG1114C: Mishima K, Nishikawa R, Narita Y, Mizusawa J, Sumi M, Koga T, Sasaki N, Kinoshita M, Nagane M, Arakawa Y, Yoshimoto K, Shibahara I, Shinojima N, Asano K, Tsurubuchi T, Sasaki H, Asai A, Sasayama T, Momii Y, Sasaki A, Nakamura S, Kojima M, Tamaru JI, Tsuchiya K, Gomyo M, Abe K, Natsumeda M, Yamasaki F, Katayama H, Fukuda H. Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C. Neuro Oncol. 2023 Apr 6;25(4):687-698. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed jRCTs031180207
Relapsed or refractory, salvage therapy
High-dose Cytarabine monotherapy (HiDAC)
HiDAC: High Dose Ara-C (Cytarabine)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Thiel et al. 2010 (G-PCNSL-SG-1) | 2000-2009 | Non-randomized part of phase 3 RCT |
Preceding treatment
- G-PCNSL-SG-1, before 2006: Non-response to High-dose methotrexate induction
- G-PCNSL-SG-1, after 2006: Non-response to Methotrexate & Ifosfamide induction
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 dosing details in manuscript have been reviewed by our editors PubMed NCT00153530
- 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
Cytarabine & Etoposide (CYVE)
CYVE: CYtarabine, VEpesid (Etoposide)
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Soussain et al. 2001 | 1992-1995 | Pilot, >20 pts |
Soussain et al. 2008 | 2000-2005 | Phase 2 |
Chemotherapy
- Cytarabine (Ara-C) 2000 mg/m2 IV over 3 hours once per day on days 2 to 5
- Cytarabine (Ara-C) 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
- Soussain et al. 2008, responders: Bu/TT/Cy, then autologous hematopoietic stem cell transplant consolidation
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Colombat et al. 2006 | 1999-2001 | Phase 2 |
Preceding treatment
- Non-response to MVBP induction 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
- Whole-brain irradiation consolidation
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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors PubMed
Ifosfamide & Methotrexate
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Fischer et al. 2008 | 2002-07 to 2007-08 | 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 therapy
- Mesna (Mesnex) for prophylaxis of hemorrhagic cystitis
- Leucovorin (Folinic acid) rescue starting 24 hours after start of methotrexate infusion
- Sodium bicarbonate IV or PO 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.
Up to 8 cycles (reference did not list timing/criteria to be used for next cycle of therapy)
Dose and schedule modifications
- 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.
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 dosing details in manuscript have been reviewed by our editors PubMed
Whole brain irradiation
Regimen variant #1, 3000 cGy
Study | Dates of enrollment | Evidence |
---|---|---|
Colombat et al. 2006 | 1999-2001 | Phase 2 |
Preceding treatment
- CYVE salvage
Radiotherapy
- Whole-brain irradiation to 3000 cGy in 180 cGy fractions plus 1000 cGy boost to the tumor bed
One course
Regimen variant #2, 3600 cGy
Study | Dates of enrollment | Evidence |
---|---|---|
Nguyen et al. 2005 | 1994-2003 | Phase 2 |
Note: The authors do not clearly describe a pre-determined dosing protocol but report that the most common fraction size was 150 cGy.
Regimen variant #3, 3600 cGy + 1000 cGy boost
Study | Dates of enrollment | Evidence |
---|---|---|
Nguyen et al. 2005 | 1994-2003 | Phase 2 |
Note: The authors do not clearly describe a pre-determined dosing protocol but report that the most common fraction size was 150 cGy.
Radiotherapy
- Whole-brain irradiation: median dose 3600 cGy (range 19.6 to 4000 cGy) + 1000 cGy (range 10 to 2160 cGy)
One course
Regimen variant #4, 4500 cGy
Study | Dates of enrollment | Evidence |
---|---|---|
Thiel et al. 2010 (G-PCNSL-SG-1) | 2000-2009 | Non-randomized part of phase 3 RCT |
Preceding treatment
- G-PCNSL-SG-1, before 2006: Non-response to high-dose MTX induction x 6
- G-PCNSL-SG-1, after 2006: Non-response to High-dose methotrexate & ifosfamide induction x 6
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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00153530
- 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
Bu/TT/Cy: Busulfan, ThioTepa, Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Soussain et al. 2001 | 1992-1995 | Pilot, >20 pts |
Soussain et al. 2008 | 2000-2005 | Phase 2 |
Preceding treatment
- CYVE salvage x 2
Chemotherapy
- Busulfan (Myleran) by the following age-based criteria:
- 60 years old or younger: 10 mg/kg PO or 8 mg/kg IV once per day on days -6, -5, and -4
- 60 years old or older: 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 therapy
- Clonazepam (Klonopin) 2 mg/day IV from the first day of busulfan until completion of busulfan
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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors PubMed
Relapsed or refractory, subsequent lines of therapy
Rituximab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Batchelor et al. 2011 (NABTT-2201) | 2004 to not reported | Pilot, fewer than 20 pts |
References
- NABTT-2201: 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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00072449
Temozolomide monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Reni et al. 2007 | 2000-2005 | Phase 2 |
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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
Temsirolimus monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Korfel et al. 2016 (TemPCNSL) | 2009-2014 | Phase 2 |
Note: This is the dose used in stage 2 of this two-stage protocol.
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 dosing details in manuscript have been reviewed by our editors PubMed NCT00942747
Topotecan monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Voloschin et al. 2008 | 1998-2002 | Phase 2, fewer than 20 pts |
Fischer et al. 2006 | 2000-2004 | Phase 2 |
Chemotherapy
- Topotecan (Hycamtin) 1.5 mg/m2 IV over 30 minutes once per day on days 1 to 5
Supportive therapy
- Voloschin et al. 2008: Ondansetron (Zofran) (dose/route not specified) prior to topotecan
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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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. link to original article PubMed