Difference between revisions of "Diffuse large B-cell lymphoma - historical"
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[[#top|Back to Top]] | [[#top|Back to Top]] | ||
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− | The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only | + | The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the [[Diffuse_large_B-cell_lymphoma|main DLBCL page]] for current regimens. |
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
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===References=== | ===References=== | ||
# Monfardini S, Tancini G, De Lena M, Villa E, Valagussa P, Bonadonna G. Cyclophosphamide, vincristine, and prednisone (CVP) versus adriamycin, bleomycin, and prednisone (ABP) in stage IV non-Hodgkin's lymphomas. Med Pediatr Oncol. 1977;3(1):67-74. [https://doi.org/10.1002/mpo.2950030110 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/65728/ PubMed] | # Monfardini S, Tancini G, De Lena M, Villa E, Valagussa P, Bonadonna G. Cyclophosphamide, vincristine, and prednisone (CVP) versus adriamycin, bleomycin, and prednisone (ABP) in stage IV non-Hodgkin's lymphomas. Med Pediatr Oncol. 1977;3(1):67-74. [https://doi.org/10.1002/mpo.2950030110 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/65728/ PubMed] | ||
− | == | + | ==ACEP {{#subobject:e05345|Regimen=1}}== |
− | + | ACEP: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone | |
<div class="toccolours" style="background-color:#ee6b6e"> | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:5ac5a4|Variant=1}}=== | ===Regimen {{#subobject:5ac5a4|Variant=1}}=== | ||
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|style="background-color:#1a9851"|Phase 3 (E-esc) | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
|[[#CHOP|CHOP]], then [[Diffuse_large_B-cell_lymphoma#Radiation_therapy|RT]] | |[[#CHOP|CHOP]], then [[Diffuse_large_B-cell_lymphoma#Radiation_therapy|RT]] | ||
− | |style="background-color:#1a9850"|Superior OS (secondary endpoint)<br>OS60: 90% vs 81% | + | |style="background-color:#1a9850"|Superior OS (secondary endpoint)<br>OS60: 90% vs 81%<br><br>Superior EFS (primary endpoint) |
|- | |- | ||
|[https://doi.org/10.1093/annonc/mdp237 Haioun et al. 2009 (LNH 98-3)] | |[https://doi.org/10.1093/annonc/mdp237 Haioun et al. 2009 (LNH 98-3)] | ||
|1999-2004 | |1999-2004 | ||
|style="background-color:#1a9851"|Phase 3 (C) | |style="background-color:#1a9851"|Phase 3 (C) | ||
− | |[[# | + | |[[#ACEP|ACEP]] |
|style="background-color:#ffffbf"|Did not meet endpoint of OS | |style="background-color:#ffffbf"|Did not meet endpoint of OS | ||
|- | |- | ||
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|- | |- | ||
|} | |} | ||
− | ''Note: this regimen | + | ''Note: this regimen was referred to as "intensified CHOP-Bleo" in the original manuscript, but bears more resemblance to ACVBP induction and is therefore re-named as ACVBP.'' |
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
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**Less than 75 kg: 300 mcg SC once per day on days 4 to 13 | **Less than 75 kg: 300 mcg SC once per day on days 4 to 13 | ||
**75 kg or more: 480 mcg SC once per day on days 4 to 13 | **75 kg or more: 480 mcg SC once per day on days 4 to 13 | ||
− | '''14-day cycle for 6 cycles''' | + | '''14-day cycle for 6 cycles'''; next cycle to start as long as WBC count is greater than 2.5 x 10<sup>9</sup>/L and platelets greater than 80 x 10<sup>9</sup>/L |
</div> | </div> | ||
<div class="toccolours" style="background-color:#cbd5e7"> | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *NHL-B1, patients with initial bulky disease (mass conglomerate at least 7.5 cm) received: [[Diffuse_large_B-cell_lymphoma#Radiation_therapy|RT]] consolidation x | + | *NHL-B1, patients with initial bulky disease (mass conglomerate at least 7.5 cm) received: [[Diffuse_large_B-cell_lymphoma#Radiation_therapy|RT]] consolidation x 3600 cGy to extranodal sites of disease when possible |
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
Line 503: | Line 503: | ||
# '''NHL-B2:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. [http://www.bloodjournal.org/content/104/3/634.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15016643/ PubMed] | # '''NHL-B2:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. [http://www.bloodjournal.org/content/104/3/634.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15016643/ PubMed] | ||
# Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648042/ PubMed] | # Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648042/ PubMed] | ||
− | ## '''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial Group. Lancet Oncol. 2011 Oct;12(11):1013-22. [https://doi.org/10.1016/S1470-2045%2811%2970235-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21940214/ PubMed] | + | ## '''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. Epub 2011 Sep 21. [https://doi.org/10.1016/S1470-2045%2811%2970235-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21940214/ PubMed] |
==CHOEP-21 {{#subobject:cad12b|Regimen=1}}== | ==CHOEP-21 {{#subobject:cad12b|Regimen=1}}== | ||
CHOEP-21: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone every '''<u>21</u>''' days | CHOEP-21: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone every '''<u>21</u>''' days | ||
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====Supportive therapy==== | ====Supportive therapy==== | ||
*[[Filgrastim (Neupogen)]] by discretion of ordering physician | *[[Filgrastim (Neupogen)]] by discretion of ordering physician | ||
− | '''21-day cycle for 4 to 6 cycles''' | + | '''21-day cycle for 4 to 6 cycles'''; next cycle to start as long as WBC is >2.5 and platelets >80 |
</div> | </div> | ||
<div class="toccolours" style="background-color:#cbd5e7"> | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *NHL-B1, patients with initial bulky disease (mass conglomerate at least 7.5 cm) received: [[Diffuse_large_B-cell_lymphoma#Radiation_therapy|RT]] consolidation x | + | *NHL-B1, patients with initial bulky disease (mass conglomerate at least 7.5 cm) received: [[Diffuse_large_B-cell_lymphoma#Radiation_therapy|RT]] consolidation x 3600 cGy to extranodal sites of disease when possible |
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
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# '''NHL-B2:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. [http://www.bloodjournal.org/content/104/3/634.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15016643/ PubMed] | # '''NHL-B2:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. [http://www.bloodjournal.org/content/104/3/634.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15016643/ PubMed] | ||
# Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648042/ PubMed] | # Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648042/ PubMed] | ||
− | ## '''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. [https://doi.org/10.1016/S1470-2045%2811%2970235-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21940214/ PubMed] | + | ## '''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. Epub 2011 Sep 21. [https://doi.org/10.1016/S1470-2045%2811%2970235-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21940214/ PubMed] |
# '''DSHNHL-1999-2:''' Pfreundschuh M, Zwick C, Zeynalova S, Dührsen U, Pflüger KH, Vrieling T, Mesters R, Mergenthaler HG, Einsele H, Bentz M, Lengfelder E, Trümper L, Rübe C, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: II - Results of the randomized high-CHOEP trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Ann Oncol. 2008 Mar;19(3):545-52. Epub 2007 Dec 6. [https://doi.org/10.1093/annonc/mdm514 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18065407/ PubMed] [https://clinicaltrials.gov/study/NCT00053768 NCT00053768] | # '''DSHNHL-1999-2:''' Pfreundschuh M, Zwick C, Zeynalova S, Dührsen U, Pflüger KH, Vrieling T, Mesters R, Mergenthaler HG, Einsele H, Bentz M, Lengfelder E, Trümper L, Rübe C, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: II - Results of the randomized high-CHOEP trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Ann Oncol. 2008 Mar;19(3):545-52. Epub 2007 Dec 6. [https://doi.org/10.1093/annonc/mdm514 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18065407/ PubMed] [https://clinicaltrials.gov/study/NCT00053768 NCT00053768] | ||
==CHOP {{#subobject:4ca454|Regimen=1}}== | ==CHOP {{#subobject:4ca454|Regimen=1}}== | ||
Line 600: | Line 600: | ||
|- | |- | ||
|} | |} | ||
− | ''Note: this | + | ''Note: this was a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Note some substantial differences from typical CHOP protocols.'' |
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
Line 615: | Line 615: | ||
<div class="toccolours" style="background-color:#cbd5e7"> | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *6-MP & MTX maintenance | + | *[[#Mercaptopurine_.26_Methotrexate_888|6-MP & MTX]] maintenance |
</div></div><br> | </div></div><br> | ||
<div class="toccolours" style="background-color:#ee6b6e"> | <div class="toccolours" style="background-color:#ee6b6e"> | ||
Line 645: | Line 645: | ||
|- | |- | ||
|} | |} | ||
− | ''Note: this | + | ''Note: this was a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' |
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
Line 688: | Line 688: | ||
<div class="toccolours" style="background-color:#cbd5e7"> | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Diffuse_large_B-cell_lymphoma#Radiation_therapy|IFRT]] consolidation x | + | *Bonnet et al. 2007: [[Diffuse_large_B-cell_lymphoma#Radiation_therapy|IFRT]] consolidation x 4000 cGy versus [[Diffuse_large_B-cell_lymphoma#Observation|no further treatment]] |
</div></div><br> | </div></div><br> | ||
<div class="toccolours" style="background-color:#ee6b6e"> | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | |||
===Regimen variant #4, 6 cycles, 100 mg prednisone {{#subobject:9e770b|Variant=1}}=== | ===Regimen variant #4, 6 cycles, 100 mg prednisone {{#subobject:9e770b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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<div class="toccolours" style="background-color:#cbd5e7"> | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *NHL-B2, patients with "lymphoma masses or conglomerates with a diameter ≥7.5 cm) or extranodal involvement": [[Diffuse_large_B-cell_lymphoma#Radiation_therapy|RT]] consolidation x | + | *NHL-B2, patients with "lymphoma masses or conglomerates with a diameter ≥7.5 cm) or extranodal involvement": [[Diffuse_large_B-cell_lymphoma#Radiation_therapy|RT]] consolidation x 3600 cGy to areas of initial bulky disease |
</div></div><br> | </div></div><br> | ||
<div class="toccolours" style="background-color:#ee6b6e"> | <div class="toccolours" style="background-color:#ee6b6e"> | ||
Line 1,022: | Line 1,023: | ||
# Jerkeman M, Anderson H, Cavallin-Ståhl E, Dictor M, Hagberg H, Johnson A, Kaasa S, Kvaløy S, Sundström C, Akerman M; Nordic Lymphoma Group. CHOP versus MACOP-B in aggressive lymphoma--a Nordic Lymphoma Group randomised trial. Ann Oncol. 1999 Sep;10(9):1079-86. [https://doi.org/10.1023/a:1008392528248 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/10572606/ PubMed] | # Jerkeman M, Anderson H, Cavallin-Ståhl E, Dictor M, Hagberg H, Johnson A, Kaasa S, Kvaløy S, Sundström C, Akerman M; Nordic Lymphoma Group. CHOP versus MACOP-B in aggressive lymphoma--a Nordic Lymphoma Group randomised trial. Ann Oncol. 1999 Sep;10(9):1079-86. [https://doi.org/10.1023/a:1008392528248 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/10572606/ PubMed] | ||
# '''LNH 98-5:''' Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C; Groupe d'Etude des Lymphomes de l'Adulte. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. [https://doi.org/10.1056/NEJMoa011795 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11807147/ PubMed] | # '''LNH 98-5:''' Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C; Groupe d'Etude des Lymphomes de l'Adulte. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. [https://doi.org/10.1056/NEJMoa011795 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11807147/ PubMed] | ||
− | ## '''Update:''' Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. [https://doi.org/10.1200/jco.2005.09.131 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15867204/ PubMed] | + | ## '''Update:''' Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. Epub 2005 May 2. [https://doi.org/10.1200/jco.2005.09.131 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15867204/ PubMed] |
− | ## '''Update:''' Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010 Sep 23;116(12):2040-5. [http://www.bloodjournal.org/content/116/12/2040.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951853/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20548096/ PubMed] | + | ## '''Update:''' Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010 Sep 23;116(12):2040-5. Epub 2010 Jun 14. [http://www.bloodjournal.org/content/116/12/2040.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951853/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20548096/ PubMed] |
## '''Update:''' Mounier N, Heutte N, Thieblemont C, Briere J, Gaulard P, Feugier P, Ghesquieres H, Van Den Neste E, Robu D, Tilly H, Bouabdallah R, Safar V, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte. Ten-year relative survival and causes of death in elderly patients treated with R-CHOP or CHOP in the GELA LNH-985 trial. Clin Lymphoma Myeloma Leuk. 2012 Jun;12(3):151-4. Epub 2012 Feb 1. [https://doi.org/10.1016/j.clml.2011.11.004 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22301063/ PubMed] | ## '''Update:''' Mounier N, Heutte N, Thieblemont C, Briere J, Gaulard P, Feugier P, Ghesquieres H, Van Den Neste E, Robu D, Tilly H, Bouabdallah R, Safar V, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte. Ten-year relative survival and causes of death in elderly patients treated with R-CHOP or CHOP in the GELA LNH-985 trial. Clin Lymphoma Myeloma Leuk. 2012 Jun;12(3):151-4. Epub 2012 Feb 1. [https://doi.org/10.1016/j.clml.2011.11.004 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22301063/ PubMed] | ||
# Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003 Dec 15;102(13):4284-9. Epub 2003 Aug 14. [http://www.bloodjournal.org/content/102/13/4284.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12920037/ PubMed] | # Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003 Dec 15;102(13):4284-9. Epub 2003 Aug 14. [http://www.bloodjournal.org/content/102/13/4284.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12920037/ PubMed] | ||
Line 1,032: | Line 1,033: | ||
# '''LNH 93-01:''' Reyes F, Lepage E, Ganem G, Molina TJ, Brice P, Coiffier B, Morel P, Ferme C, Bosly A, Lederlin P, Laurent G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med. 2005 Mar 24;352(12):1197-205. [https://doi.org/10.1056/NEJMoa042040 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15788496/ PubMed] | # '''LNH 93-01:''' Reyes F, Lepage E, Ganem G, Molina TJ, Brice P, Coiffier B, Morel P, Ferme C, Bosly A, Lederlin P, Laurent G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med. 2005 Mar 24;352(12):1197-205. [https://doi.org/10.1056/NEJMoa042040 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15788496/ PubMed] | ||
# Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648042/ PubMed] | # Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648042/ PubMed] | ||
− | ## '''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. [https://doi.org/10.1016/S1470-2045%2811%2970235-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21940214/ PubMed] | + | ## '''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. Epub 2011 Sep 21. [https://doi.org/10.1016/S1470-2045%2811%2970235-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21940214/ PubMed] |
# '''ECOG E4494:''' Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. [https://doi.org/10.1200/jco.2005.05.1003 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16754935/ PubMed] [https://clinicaltrials.gov/study/NCT00003150 NCT00003150] | # '''ECOG E4494:''' Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. [https://doi.org/10.1200/jco.2005.05.1003 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16754935/ PubMed] [https://clinicaltrials.gov/study/NCT00003150 NCT00003150] | ||
# '''MISTRAL:''' Betticher DC, Martinelli G, Radford JA, Kaufmann M, Dyer MJ, Kaiser U, Aulitzky WE, Beck J, von Rohr A, Kovascovics T, Cogliatti SB, Cina S, Maibach R, Cerny T, Linch DC. Sequential high dose chemotherapy as initial treatment for aggressive sub-types of non-Hodgkin lymphoma: results of the international randomized phase III trial (MISTRAL). Ann Oncol. 2006 Oct;17(10):1546-52. Epub 2006 Aug 3. [https://doi.org/10.1093/annonc/mdl153 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16888080/ PubMed] [https://clinicaltrials.gov/study/NCT00003215 NCT00003215] | # '''MISTRAL:''' Betticher DC, Martinelli G, Radford JA, Kaufmann M, Dyer MJ, Kaiser U, Aulitzky WE, Beck J, von Rohr A, Kovascovics T, Cogliatti SB, Cina S, Maibach R, Cerny T, Linch DC. Sequential high dose chemotherapy as initial treatment for aggressive sub-types of non-Hodgkin lymphoma: results of the international randomized phase III trial (MISTRAL). Ann Oncol. 2006 Oct;17(10):1546-52. Epub 2006 Aug 3. [https://doi.org/10.1093/annonc/mdl153 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16888080/ PubMed] [https://clinicaltrials.gov/study/NCT00003215 NCT00003215] | ||
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<div class="toccolours" style="background-color:#cbd5e7"> | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *RICOVER-60, patients with "Initial bulky disease" (lymphoma masses or conglomerates with a diameter of at least 7.5 cm or extranodal involvement): [[#Radiation_therapy|RT]] consolidation x | + | *RICOVER-60, patients with "Initial bulky disease" (lymphoma masses or conglomerates with a diameter of at least 7.5 cm or extranodal involvement): [[#Radiation_therapy|RT]] consolidation x 3600 cGy to areas of initial bulky disease |
</div></div><br> | </div></div><br> | ||
<div class="toccolours" style="background-color:#ee6b6e"> | <div class="toccolours" style="background-color:#ee6b6e"> | ||
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<div class="toccolours" style="background-color:#cbd5e7"> | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *RICOVER-60, patients with "Initial bulky disease" (lymphoma masses or conglomerates with a diameter of at least 7.5 cm or extranodal involvement): [[#Radiation_therapy|RT]] consolidation x | + | *RICOVER-60, patients with "Initial bulky disease" (lymphoma masses or conglomerates with a diameter of at least 7.5 cm or extranodal involvement): [[#Radiation_therapy|RT]] consolidation x 3600 cGy to areas of initial bulky disease |
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
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<!-- Presented orally and in abstract form at the 47th annual meeting of the American Society of Hematology, Atlanta, Georgia, December 11, 2005. --> | <!-- Presented orally and in abstract form at the 47th annual meeting of the American Society of Hematology, Atlanta, Georgia, December 11, 2005. --> | ||
# '''HOVON-26:''' Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, Ossenkoppele GJ, Doorduijn JK, Sonneveld P, van Imhoff GW. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007 Apr 1;109(7):2759-66. [http://www.bloodjournal.org/content/109/7/2759.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17132720/ PubMed] | # '''HOVON-26:''' Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, Ossenkoppele GJ, Doorduijn JK, Sonneveld P, van Imhoff GW. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007 Apr 1;109(7):2759-66. [http://www.bloodjournal.org/content/109/7/2759.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17132720/ PubMed] | ||
− | # '''RICOVER-60:''' Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. [https://doi.org/10.1016/S1470-2045%2808%2970002-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18226581/ PubMed] [https://clinicaltrials.gov/study/NCT00052936 NCT00052936] | + | # '''RICOVER-60:''' Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. Epub 2008 Jan 15. [https://doi.org/10.1016/S1470-2045%2808%2970002-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18226581/ PubMed] [https://clinicaltrials.gov/study/NCT00052936 NCT00052936] |
==CHOP Modified {{#subobject:bb947a|Regimen=1}}== | ==CHOP Modified {{#subobject:bb947a|Regimen=1}}== | ||
Line 1,273: | Line 1,274: | ||
|- | |- | ||
|} | |} | ||
− | ''Note: This regimen | + | ''Note: This regimen was designed for elderly patients and is of lower intensity than standard CHOP.'' |
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
Line 1,426: | Line 1,427: | ||
====Glucocorticoid therapy==== | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5 | *[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
+ | '''21- to 28-day cycle for 8 cycles''' | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
# '''EORTC 20751:''' Burgers JM, Somers R, Quasim MM, van Glabbekke M. Report on the EORTC 20751 lymphoma trial. Int J Radiat Oncol Biol Phys. 1983 Jan;9(1):11-5. [https://doi.org/10.1016/0360-3016(83)90201-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6341333/ PubMed] | # '''EORTC 20751:''' Burgers JM, Somers R, Quasim MM, van Glabbekke M. Report on the EORTC 20751 lymphoma trial. Int J Radiat Oncol Biol Phys. 1983 Jan;9(1):11-5. [https://doi.org/10.1016/0360-3016(83)90201-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6341333/ PubMed] | ||
# Carde P, Meerwaldt JH, van Glabbeke M, Somers R, Monconduit M, Thomas J, de Wolf-Peeters C, de Pauw B, Tanguy A, Kluin-Nelemans JC, Noordijk EM, Regnier R, Bron D, Lustman-Marechal J, Caillou B, Bosq J, van Heerde P, van Unnik JAM, Burgers MV, Hayat M, Cosset JM, van der Schueren E, Wagener J, Hagenbeek A, Cattan A, Duez N, Tubiana M; [[Study_Groups#EORTC|EORTC]] Lymphoma Group. Superiority of second over first generation chemotherapy in a randomized trial for stage III-IV intermediate and high-grade non-Hodgkin's lymphoma (NHL): the 1980-1985 EORTC trial. Ann Oncol. 1991 Jun;2(6):431-5. [https://doi.org/10.1093/oxfordjournals.annonc.a057979 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1722697/ PubMed] | # Carde P, Meerwaldt JH, van Glabbeke M, Somers R, Monconduit M, Thomas J, de Wolf-Peeters C, de Pauw B, Tanguy A, Kluin-Nelemans JC, Noordijk EM, Regnier R, Bron D, Lustman-Marechal J, Caillou B, Bosq J, van Heerde P, van Unnik JAM, Burgers MV, Hayat M, Cosset JM, van der Schueren E, Wagener J, Hagenbeek A, Cattan A, Duez N, Tubiana M; [[Study_Groups#EORTC|EORTC]] Lymphoma Group. Superiority of second over first generation chemotherapy in a randomized trial for stage III-IV intermediate and high-grade non-Hodgkin's lymphoma (NHL): the 1980-1985 EORTC trial. Ann Oncol. 1991 Jun;2(6):431-5. [https://doi.org/10.1093/oxfordjournals.annonc.a057979 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1722697/ PubMed] | ||
+ | |||
==CHVmP-VB {{#subobject:0a9c69|Regimen=1}}== | ==CHVmP-VB {{#subobject:0a9c69|Regimen=1}}== | ||
CHVmP-VB: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>Vm</u>'''26 (Teniposide), '''<u>P</u>'''rednisone, '''<u>V</u>'''incristine, '''<u>B</u>'''leomycin | CHVmP-VB: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>Vm</u>'''26 (Teniposide), '''<u>P</u>'''rednisone, '''<u>V</u>'''incristine, '''<u>B</u>'''leomycin | ||
Line 1,463: | Line 1,466: | ||
====Glucocorticoid therapy==== | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5 | *[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
+ | '''21-day cycle for 8 cycles''' | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
Line 1,492: | Line 1,496: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 650 mg/m<sup>2</sup> IV once per day on days 1 & 8 |
− | *[[Vincristine (Oncovin)]] | + | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8 |
− | *[[Procarbazine (Matulane)]] | + | *[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14 |
====Glucocorticoid therapy==== | ====Glucocorticoid therapy==== | ||
− | *[[Prednisone (Sterapred)]] | + | *[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 14 |
+ | '''28-day cycle for 6 cycles''' | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
# Stein RS, Moran EM, Desser RK, Miller JB, Golomb HM, Ultmann JE. Combination chemotherapy of lymphomas other than Hodgkin's disease. Ann Intern Med. 1974 Nov;81(5):601-8. [https://doi.org/10.7326/0003-4819-81-5-601 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4608355/ PubMed] | # Stein RS, Moran EM, Desser RK, Miller JB, Golomb HM, Ultmann JE. Combination chemotherapy of lymphomas other than Hodgkin's disease. Ann Intern Med. 1974 Nov;81(5):601-8. [https://doi.org/10.7326/0003-4819-81-5-601 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4608355/ PubMed] | ||
− | # DeVita VT Jr, Canellos GP, Chabner B, Schein P, Hubbard SP, Young RC. Advanced diffuse histiocytic lymphoma, a potentially curable disease. Lancet. 1975 Feb 1;1(7901):248-50. [https://doi.org/10.1016/s0140-6736(75)91142-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/46388/ PubMed] | + | # DeVita VT Jr, Canellos GP, Chabner B, Schein P, Hubbard SP, Young RC. Advanced diffuse histiocytic lymphoma, a potentially curable disease. Lancet. 1975 Feb 1;1(7901):248-50. [https://doi.org/10.1016/s0140-6736(75)91142-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/46388/ PubMed] |
+ | |||
==CNOP {{#subobject:3121b4|Regimen=1}}== | ==CNOP {{#subobject:3121b4|Regimen=1}}== | ||
CNOP: '''<u>C</u>'''yclophosphamide, '''<u>N</u>'''ovantrone (Mitoxantrone), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone | CNOP: '''<u>C</u>'''yclophosphamide, '''<u>N</u>'''ovantrone (Mitoxantrone), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone | ||
Line 1,911: | Line 1,917: | ||
|[https://doi.org/10.1200/JCO.2005.11.075 Laver et al. 2005 (POG 9315)] | |[https://doi.org/10.1200/JCO.2005.11.075 Laver et al. 2005 (POG 9315)] | ||
|1994-2000 | |1994-2000 | ||
− | | style="background-color:#91cf61" |Non-randomized part of RCT | + | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
Line 2,024: | Line 2,030: | ||
# Gianni AM, Bregni M, Siena S, Brambilla C, Di Nicola M, Lombardi F, Gandola L, Tarella C, Pileri A, Ravagnani F, Valagussa P, Bonadonna G. High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. N Engl J Med. 1997 May 1;336(18):1290-7. [https://doi.org/10.1056/NEJM199705013361804 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9113932/ PubMed] | # Gianni AM, Bregni M, Siena S, Brambilla C, Di Nicola M, Lombardi F, Gandola L, Tarella C, Pileri A, Ravagnani F, Valagussa P, Bonadonna G. High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. N Engl J Med. 1997 May 1;336(18):1290-7. [https://doi.org/10.1056/NEJM199705013361804 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9113932/ PubMed] | ||
# Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648042/ PubMed] | # Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648042/ PubMed] | ||
− | ## '''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. [https://doi.org/10.1016/S1470-2045%2811%2970235-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21940214/ PubMed] | + | ## '''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. Epub 2011 Sep 21. [https://doi.org/10.1016/S1470-2045%2811%2970235-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21940214/ PubMed] |
==m-BACOD {{#subobject:c52d3a|Regimen=1}}== | ==m-BACOD {{#subobject:c52d3a|Regimen=1}}== | ||
m-BACOD: '''<u>m</u>'''ethotrexate (moderate dose), '''<u>B</u>'''leomycin, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>D</u>'''examethasone | m-BACOD: '''<u>m</u>'''ethotrexate (moderate dose), '''<u>B</u>'''leomycin, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>D</u>'''examethasone | ||
Line 2,118: | Line 2,124: | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: The abstract does not contain treatment details, and the original manuscript is not available online.'' | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
Line 2,130: | Line 2,137: | ||
===References=== | ===References=== | ||
# Gherlinzoni F, Guglielmi C, Mazza P, Amadori S, Mandelli F, Tura S. Phase III comparative trial (m-BACOD v m-BNCOD) in the treatment of stage II to IV non-Hodgkin's lymphomas with intermediate- or high-grade histology. Semin Oncol. 1990 Dec;17(6 Suppl 10):3-8. [https://pubmed.ncbi.nlm.nih.gov/1701924/ PubMed] | # Gherlinzoni F, Guglielmi C, Mazza P, Amadori S, Mandelli F, Tura S. Phase III comparative trial (m-BACOD v m-BNCOD) in the treatment of stage II to IV non-Hodgkin's lymphomas with intermediate- or high-grade histology. Semin Oncol. 1990 Dec;17(6 Suppl 10):3-8. [https://pubmed.ncbi.nlm.nih.gov/1701924/ PubMed] | ||
+ | |||
==P/DOCE {{#subobject:375d4a|Regimen=1}}== | ==P/DOCE {{#subobject:375d4a|Regimen=1}}== | ||
P/DOCE: '''<u>P</u>'''rednisone, '''<u>D</u>'''oxorubicin, '''<u>O</u>'''ncovin (Vincristine), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, | P/DOCE: '''<u>P</u>'''rednisone, '''<u>D</u>'''oxorubicin, '''<u>O</u>'''ncovin (Vincristine), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, | ||
Line 2,144: | Line 2,152: | ||
|- | |- | ||
|} | |} | ||
− | ''Note: although the drugs are the same as those used in CHOEP, the doses are significantly different and this | + | ''Note: although the drugs are the same as those used in CHOEP, the doses are significantly different and this was intended for elderly persons (65+ years of age). Although the original paper described this as an 8-week protocol, we express it here in cyclic fashion.'' |
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Glucocorticoid therapy==== | ====Glucocorticoid therapy==== | ||
− | *[[Prednisone (Sterapred)]] 50 mg/day PO on days 1 to 10 | + | *[[Prednisone (Sterapred)]] 50 mg/day PO on days 1 to 10 |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per | + | *[[Doxorubicin (Adriamycin)]] as follows: |
− | *[[Vincristine (Oncovin)]] 1.2 mg/m<sup>2</sup> IV once | + | **Cycles 1 & 3: 40 mg/m<sup>2</sup> IV once per day on days 1 & 8 |
− | *[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV once | + | *[[Vincristine (Oncovin)]] 1.2 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV once on day | + | *[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV once on day 1 |
− | ''' | + | *[[Etoposide (Vepesid)]] as follows: |
+ | **Cycle 2: 50 mg/m<sup>2</sup> IV once on day 1, then 100 mg/m<sup>2</sup> PO once per day on days 2 to 5 | ||
+ | '''21-day cycle for 3 cycles''' | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
Line 2,272: | Line 2,282: | ||
# '''BNLI CHOPVPMITCEBO-GOODRISK:''' Burton C, Linch D, Hoskin P, Milligan D, Dyer MJ, Hancock B, Mouncey P, Smith P, Qian W, MacLennan K, Jack A, Webb A, Cunningham D. A phase III trial comparing CHOP to PMitCEBO with or without G-CSF in patients aged 60 plus with aggressive non-Hodgkin's lymphoma. Br J Cancer. 2006 Mar 27;94(6):806-13. [https://doi.org/10.1038/sj.bjc.6602975 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3216418/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16508640/ PubMed] [https://clinicaltrials.gov/study/NCT00005867 NCT00005867] | # '''BNLI CHOPVPMITCEBO-GOODRISK:''' Burton C, Linch D, Hoskin P, Milligan D, Dyer MJ, Hancock B, Mouncey P, Smith P, Qian W, MacLennan K, Jack A, Webb A, Cunningham D. A phase III trial comparing CHOP to PMitCEBO with or without G-CSF in patients aged 60 plus with aggressive non-Hodgkin's lymphoma. Br J Cancer. 2006 Mar 27;94(6):806-13. [https://doi.org/10.1038/sj.bjc.6602975 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3216418/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16508640/ PubMed] [https://clinicaltrials.gov/study/NCT00005867 NCT00005867] | ||
#'''NCIC-CTG LY.9:''' Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648042/ PubMed] [https://clinicaltrials.gov/study/NCT00064116 NCT00064116] | #'''NCIC-CTG LY.9:''' Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648042/ PubMed] [https://clinicaltrials.gov/study/NCT00064116 NCT00064116] | ||
− | ## '''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. [https://doi.org/10.1016/S1470-2045%2811%2970235-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21940214/ PubMed] | + | ## '''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. Epub 2011 Sep 21. [https://doi.org/10.1016/S1470-2045%2811%2970235-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21940214/ PubMed] |
==ProMACE-CytaBOM {{#subobject:5285e6|Regimen=1}}== | ==ProMACE-CytaBOM {{#subobject:5285e6|Regimen=1}}== | ||
ProMACE-CytaBOM: '''<u>Pro</u>'''lix (Prednisone), '''<u>M</u>'''ethotrexate, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>Cyta</u>'''rabine, '''<u>B</u>'''leomycin, '''<u>O</u>'''ncovin (Vincristine), '''<u>M</u>'''ethotrexate | ProMACE-CytaBOM: '''<u>Pro</u>'''lix (Prednisone), '''<u>M</u>'''ethotrexate, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>Cyta</u>'''rabine, '''<u>B</u>'''leomycin, '''<u>O</u>'''ncovin (Vincristine), '''<u>M</u>'''ethotrexate | ||
Line 2,697: | Line 2,707: | ||
<div class="toccolours" style="background-color:#cbd5e8"> | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#CEEP|CEEP]] x 2 | + | *Induction [[#CEEP|CEEP]] x 2 |
</div> | </div> | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
Line 2,743: | Line 2,753: | ||
|- | |- | ||
|} | |} | ||
− | ''Note: Velasquez et al. 1988 | + | ''Note: Velasquez et al. 1988 reported giving 6 to 10 courses, usually 4 courses beyond maximum response. To our knowledge, this regimen was not tested as an experimental arm in a RCT prior to becoming a standard comparator arm.'' |
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Glucocorticoid therapy==== | ====Glucocorticoid therapy==== | ||
Line 2,767: | Line 2,777: | ||
# '''PARMA:''' Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin F. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. [https://doi.org/10.1056/NEJM199512073332305 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/7477169/ PubMed] | # '''PARMA:''' Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin F. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. [https://doi.org/10.1056/NEJM199512073332305 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/7477169/ PubMed] | ||
# Josting A, Sieniawski M, Glossmann JP, Staak O, Nogova L, Peters N, Mapara M, Dörken B, Ko Y, Metzner B, Kisro J, Diehl V, Engert A. High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study. Ann Oncol. 2005 Aug;16(8):1359-65. Epub 2005 Jun 6. [https://doi.org/10.1093/annonc/mdi248 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15939712/ PubMed] | # Josting A, Sieniawski M, Glossmann JP, Staak O, Nogova L, Peters N, Mapara M, Dörken B, Ko Y, Metzner B, Kisro J, Diehl V, Engert A. High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study. Ann Oncol. 2005 Aug;16(8):1359-65. Epub 2005 Jun 6. [https://doi.org/10.1093/annonc/mdi248 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15939712/ PubMed] | ||
+ | ==DHAP/VIM {{#subobject:e57948|Regimen=1}}== | ||
+ | DHAP/VIM: '''<u>D</u>'''examethasone, '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>P</u>'''latinol (Cisplatin) alternating with '''<u>V</u>'''P-16 (Etoposide), '''<u>I</u>'''fosfamide, '''<u>M</u>'''ethotrexate | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen {{#subobject:f46b7f|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !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]] | ||
+ | |- | ||
+ | |[http://www.bloodjournal.org/content/111/2/537.long Vellenga et al. 2007 (HOVON-44)] | ||
+ | |2000-2005 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[Diffuse_large_B-cell_lymphoma#R-DHAP.2FR-VIM|R-DHAP/R-VIM]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: per the paper, "in case patients were non-responsive to DHAP but responsive to VIM, it was allowed to repeat the VIM regimen as the third cycle of reinduction chemotherapy." No statement was made as to whether Mesna was used in the VIM protocol.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Glucocorticoid therapy, DHAP portion (cycles 1 & 3)==== | ||
+ | *[[Dexamethasone (Decadron)]] 40 mg IV or PO once per day on days 1 to 4 | ||
+ | ====Chemotherapy, DHAP portion (cycles 1 & 3)==== | ||
+ | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m<sup>2</sup>) | ||
+ | *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 | ||
+ | ====Chemotherapy, VIM portion (cycle 2)==== | ||
+ | *[[Etoposide (Vepesid)]] 90 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | ||
+ | *[[Ifosfamide (Ifex)]] 1200 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
+ | *[[Methotrexate (MTX)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 5 | ||
+ | '''28-day cycle for 3 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *HOVON-44, responders: Stem-cell mobilization, then [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''HOVON-44:''' Vellenga E, van Putten WL, van 't Veer MB, Zijlstra JM, Fibbe WE, van Oers MH, Verdonck LF, Wijermans PW, van Imhoff GW, Lugtenburg PJ, Huijgens PC. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood. 2008 Jan 15;111(2):537-43. Epub 2007 Oct 30. [http://www.bloodjournal.org/content/111/2/537.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17971487/ PubMed] [https://clinicaltrials.gov/study/NCT00012051 NCT00012051] | ||
+ | |||
==EPIC (carboplatin) {{#subobject:9fugh4|Regimen=1}}== | ==EPIC (carboplatin) {{#subobject:9fugh4|Regimen=1}}== | ||
EPIC: '''<u>E</u>'''toposide, '''<u>P</u>'''rednisolone, '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin | EPIC: '''<u>E</u>'''toposide, '''<u>P</u>'''rednisolone, '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin | ||
Line 2,849: | Line 2,897: | ||
==MINE {{#subobject:aff118|Regimen=1}}== | ==MINE {{#subobject:aff118|Regimen=1}}== | ||
MINE: '''<u>M</u>'''esna, '''<u>I</u>'''fosfamide, '''<u>N</u>'''ovantrone (Mitoxantrone), '''<u>E</u>'''toposide | MINE: '''<u>M</u>'''esna, '''<u>I</u>'''fosfamide, '''<u>N</u>'''ovantrone (Mitoxantrone), '''<u>E</u>'''toposide | ||
+ | <br>VIM: '''<u>V</u>'''epesid (Etoposide), '''<u>I</u>'''fosfamide, '''<u>M</u>'''itoxantrone | ||
<div class="toccolours" style="background-color:#ee6b6e"> | <div class="toccolours" style="background-color:#ee6b6e"> | ||
− | ===Regimen {{#subobject:3a1597|Variant=1}}=== | + | ===Regimen variant #1 {{#subobject:3a1597|Variant=1}}=== |
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
Line 2,875: | Line 2,924: | ||
*Rodriguez et al. 1995, CR: A total of 6 cycles of MINE, then [[#ESHAP|ESHAP]] consolidation x 3 | *Rodriguez et al. 1995, CR: A total of 6 cycles of MINE, then [[#ESHAP|ESHAP]] consolidation x 3 | ||
*Rodriguez et al. 1995, PR: MINE was given to the point of maximal response, and then patients were crossed over to ESHAP. | *Rodriguez et al. 1995, PR: MINE was given to the point of maximal response, and then patients were crossed over to ESHAP. | ||
− | </div></div> | + | </div></div><br> |
− | |||
− | |||
− | |||
− | |||
<div class="toccolours" style="background-color:#ee6b6e"> | <div class="toccolours" style="background-color:#ee6b6e"> | ||
− | ===Regimen {{#subobject:9817aa|Variant=1}}=== | + | ===Regimen variant #2 {{#subobject:9817aa|Variant=1}}=== |
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
Line 2,894: | Line 2,939: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Ifosfamide (Ifex)]] 650 mg/m<sup>2</sup> IV once per day on day 1 to 3 | *[[Ifosfamide (Ifex)]] 650 mg/m<sup>2</sup> IV once per day on day 1 to 3 | ||
*[[Mitoxantrone (Novantrone)]] 3 mg/m<sup>2</sup> IV once per day on day 1 to 3 | *[[Mitoxantrone (Novantrone)]] 3 mg/m<sup>2</sup> IV once per day on day 1 to 3 | ||
+ | *[[Etoposide (Vepesid)]] 65 mg/m<sup>2</sup> IV once per day on day 1 to 3 | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
*[[Mesna (Mesnex)]] 300 mg IV three times per day on days 1 to 3 | *[[Mesna (Mesnex)]] 300 mg IV three times per day on days 1 to 3 | ||
Line 2,902: | Line 2,947: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
+ | # Rodriguez MA, Cabanillas FC, Velasquez W, Hagemeister FB, McLaughlin P, Swan F, Romaguera JE. Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP. J Clin Oncol. 1995 Jul;13(7):1734-41. [https://doi.org/10.1200/jco.1995.13.7.1734 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7602363/ PubMed] | ||
# Hopfinger G, Heinz R, Koller E, Schneider B, Pittermann E. Ifosfamide, mitoxantrone and etoposide (VIM) as salvage therapy of low toxicity in non-Hodgkin's lymphoma. Eur J Haematol. 1995 Oct;55(4):223-7. [https://doi.org/10.1111/j.1600-0609.1995.tb00261.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7589338/ PubMed] | # Hopfinger G, Heinz R, Koller E, Schneider B, Pittermann E. Ifosfamide, mitoxantrone and etoposide (VIM) as salvage therapy of low toxicity in non-Hodgkin's lymphoma. Eur J Haematol. 1995 Oct;55(4):223-7. [https://doi.org/10.1111/j.1600-0609.1995.tb00261.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7589338/ PubMed] | ||
Line 3,103: | Line 3,149: | ||
|1986-1988 | |1986-1988 | ||
|style="background-color:#1a9851"|Phase 3 (E-esc) | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
− | |[[# | + | |[[#ESHA_999|ESHA]] |
|style="background-color:#1a9850"|Superior RR | |style="background-color:#1a9850"|Superior RR | ||
|- | |- | ||
Line 3,129: | Line 3,175: | ||
# Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. [https://doi.org/10.1200/jco.1994.12.6.1169 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8201379/ PubMed] | # Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. [https://doi.org/10.1200/jco.1994.12.6.1169 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8201379/ PubMed] | ||
# Avilés A, Neri N, Huerta-Guzmán J, de Jesús Nambo M. ESHAP versus rituximab-ESHAP in frail patients with refractory diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2010 Apr;10(2):125-8. [https://doi.org/10.3816/CLML.2010.n.017 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20371445/ PubMed] | # Avilés A, Neri N, Huerta-Guzmán J, de Jesús Nambo M. ESHAP versus rituximab-ESHAP in frail patients with refractory diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2010 Apr;10(2):125-8. [https://doi.org/10.3816/CLML.2010.n.017 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20371445/ PubMed] | ||
+ | |||
==Etoposide, Ifosfamide, Methotrexate {{#subobject:d49400|Regimen=1}}== | ==Etoposide, Ifosfamide, Methotrexate {{#subobject:d49400|Regimen=1}}== | ||
IMVP-16: '''<u>I</u>'''fosfamide, '''<u>M</u>'''ethotrexate, '''<u>VP-16</u>''' (Etoposide) | IMVP-16: '''<u>I</u>'''fosfamide, '''<u>M</u>'''ethotrexate, '''<u>VP-16</u>''' (Etoposide) | ||
Line 3,195: | Line 3,242: | ||
|- | |- | ||
|} | |} | ||
− | ''Note: Third cycle intended to be followed by peripheral blood hematopoietic cell collection'' | + | ''Note: Third cycle was intended to be followed by peripheral blood hematopoietic cell collection. Carboplatin AUC was calculated based on a 12-hour creatinine clearance.'' |
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 2, '''mixed with mesna''' | *[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 2, '''mixed with mesna''' | ||
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg) IV bolus once on day 2 | *[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg) IV bolus once on day 2 | ||
− | |||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3 | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
Line 3,219: | Line 3,265: | ||
|- | |- | ||
|} | |} | ||
− | ''Note: Third cycle intended to be followed by peripheral blood hematopoietic cell collection'' | + | ''Note: Third cycle was intended to be followed by peripheral blood hematopoietic cell collection'' |
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== |
Revision as of 11:44, 18 May 2024
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main DLBCL page for current regimens.
67 regimens on this page
85 variants on this page
|
Untreated
ABP
ABP: Adriamycin (Doxorubicin), Bleomycin, Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Monfardini et al. 1977 | 1972-1974 | Phase 3 (E-switch-ic) | CVP | Did not meet endpoint of ORR |
Chemotherapy
- Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
- Bleomycin (Blenoxane) 15 mg/m2 IV once per day on days 1 & 8
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg/m2 IM once per day on days 1 to 5
21-day cycle for at least 6 cycles
References
- Monfardini S, Tancini G, De Lena M, Villa E, Valagussa P, Bonadonna G. Cyclophosphamide, vincristine, and prednisone (CVP) versus adriamycin, bleomycin, and prednisone (ABP) in stage IV non-Hodgkin's lymphomas. Med Pediatr Oncol. 1977;3(1):67-74. link to original article contains dosing details in manuscript PubMed
ACEP
ACEP: Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide, Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Dumontet et al. 2000 | 1995-1998 | Phase 2 | ||
Haioun et al. 2009 (LNH 98-3) | 1999-2004 | Phase 3 (E-de-esc) | ACVBP | Did not meet endpoint of OS |
Chemotherapy
- Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once per day on days 1 & 2
- Etoposide (Vepesid) as follows:
- Cycles 2 to 4: 150 mg/m2 IV once per day on days 1 to 3
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 (route not specified) once per day on days 1 to 5
CNS therapy, prophylaxis
- Methotrexate (MTX) 15 mg IT once on day 2
Supportive therapy
- G-CSF 5 mcg/kg/day SC on days 6 to 13
14-day cycle for 4 cycles
References
- Dumontet C, Thieblemont C, Espinouse D, Bouafia F, Hequet O, Salles G, Coiffier B. A prospective study of intensive induction therapy with high-dose consolidation in patients with aggressive non-Hodgkin's lymphoma and two or three adverse prognostic factors. Leukemia. 2000 Dec;14(12):2159-65. link to original article PubMed
- LNH 98-3: Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. link to original article contains dosing details in manuscript PubMed NCT00169169
ACOMLA
ACOMLA: Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Methotrexate, Leucovorin (Folinic acid), Ara-C (Cytarabine)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Newcomer et al. 1982 | NR in abstract | Randomized, fewer than 20 patients | CHOP-B | Seems to have inferior RFS |
Chemotherapy
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once per day on days 1, 8, 15
- Methotrexate (MTX) 120 mg/m2 IV once per day on days 22, 29, 36, 43, 50, 57, 71
- Cytarabine (Ara-C) 300 mg/m2 IV once per day on days 22, 29, 36, 43, 50, 57, 71
90-day cycle for 3 cycles
References
- Newcomer LN, Cadman EC, Nerenberg MI, Chen M, Bertino JR, Farber LR, Prosnitz LR. Randomized study comparing doxorubicin, cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (ACOMLA) with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-B) in the treatment of diffuse histiocytic lymphoma. Cancer Treat Rep. 1982 Jun;66(6):1279-84. PubMed
ACVBP
ACVBP: Adriamycin (Doxorubicin), Cyclophosphamide, Vindesine, Bleomycin, Prednisone
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tilly et al. 2000 (LNH87-1) | 1987-1993 | Phase 3 (E-esc) | m-BACOD | Did not meet primary endpoint of FFS |
Tilly et al. 2003 | 1993-1998 | Phase 3 (E-esc) | CHOP | Seems to have superior OS |
Morel et al. 2010 (LNH93-2) | 1993-1998 | Phase 3 (C) | ECVBP | Did not meet primary endpoint of EFS |
Reyes et al. 2005 (LNH 93-01) | 1993-2000 | Phase 3 (E-esc) | CHOP, then RT | Superior OS (secondary endpoint) OS60: 90% vs 81% Superior EFS (primary endpoint) |
Haioun et al. 2009 (LNH 98-3) | 1999-2004 | Phase 3 (C) | ACEP | Did not meet endpoint of OS |
Ketterer et al. 2013 (LNH03-1B) | 2003-2008 | Phase 3 (C) | R-ACVBP | Seems to have inferior PFS |
Induction
Chemotherapy
- Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
- Vindesine (Eldisine) 2 mg/m2 IV once per day on days 1 & 5
- Bleomycin (Blenoxane) 10 units IV once per day on days 1 & 5
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
CNS therapy, prophylaxis
- Methotrexate (MTX) 15 mg IT on day 2
Supportive therapy
- G-CSF or GM-CSF SC once per day on days 6 to 13
21-day cycle for 4 cycles, followed by:
Consolidation, part 1
Chemotherapy
- Methotrexate (MTX) 3000 mg/m2 IV once on day 1
Supportive therapy
- Leucovorin rescue
14-day cycle for 2 cycles, followed in 2 weeks by:
Consolidation, part 2 (EI)
Chemotherapy
- Etoposide (Vepesid) 300 mg/m2 IV once on day 1
- Ifosfamide (Ifex) 1500 mg/m2 IV once on day 1
Supportive therapy
- Mesna (Mesnex) "protection" (details not provided)
14-day cycle for 4 cycles, followed in 2 weeks by:
Consolidation, part 3
References
- LNH87-1: Tilly H, Mounier N, Lederlin P, Brière J, Dupriez B, Sebban C, Bosly A, Biron P, Nouvel C, Herbrecht R, Bordessoule D, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte. Randomized comparison of ACVBP and m-BACOD in the treatment of patients with low-risk aggressive lymphoma: the LNH87-1 study. J Clin Oncol. 2000 Mar;18(6):1309-15. link to original article PubMed
- Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003 Dec 15;102(13):4284-9. Epub 2003 Aug 14. link to original article contains dosing details in manuscript PubMed
- LNH 93-01: Reyes F, Lepage E, Ganem G, Molina TJ, Brice P, Coiffier B, Morel P, Ferme C, Bosly A, Lederlin P, Laurent G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med. 2005 Mar 24;352(12):1197-205. link to original article PubMed
- LNH 98-3: Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. link to original article PubMed NCT00169169
- LNH93-2: Morel P, Munck JN, Coiffier B, Gisselbrecht C, Ranta D, Bosly A, Tilly H, Quesnel B, Thyss A, Mounier N, Brière J, Molina T, Reyes F; GELA. Comparison of two high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone derived regimens in patients aged under 60 years with low-intermediate risk aggressive lymphoma: a final analysis of the multicenter LNH93-2 protocol. Leuk Lymphoma. 2010 Sep;51(9):1668-77. link to original article PubMed
- LNH03-1B: Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C; GELA. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. link to original article PubMed NCT00140595
ACVBP (Methylprednisolone)
ACVBP: Adriamycin (Doxorubicin), Cyclophosphamide, Vindesine, Bleomycin, MethylPrednisone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Coiffier et al. 1986 (LNH-80) | 1980-1984 | Phase 2 |
Note: this regimen was referred to as "intensified CHOP-Bleo" in the original manuscript, but bears more resemblance to ACVBP induction and is therefore re-named as ACVBP.
Chemotherapy
- Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
- Vindesine (Eldisine) 2 mg/m2 IV once per day on days 1 & 5
- Bleomycin (Blenoxane) 5 mg/m2 IV once per day on days 1 to 5
Glucocorticoid therapy
- Methylprednisolone (Solumedrol) 60 mg/m2 (route not specified) once per day on days 1 to 5
CNS therapy, prophylaxis
- Methotrexate (MTX) 15 mg IT once
15-day cycle for 3 cycles; cycles were delayed until ANC greater than 1500/μL
References
- LNH-80: Coiffier B, Bryon PA, Berger F, Archimbaud E, Ffrench M, Extra JM, Guyotat D, Fiere D, Gentilhomme O, Magaud JP, Blanc M, Peaud PY, Vuvan H, Viala JJ. Intensive and sequential combination chemotherapy for aggressive malignant lymphomas (protocol LNH-80). J Clin Oncol. 1986 Feb;4(2):147-53. link to original article contains dosing details in manuscript PubMed
BCOP
BCOP: BCNU (Carmustine), Cyclophosphamide, Oncovin (Vincristine), Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gams et al. 1985 | 1977-1981 | Phase 3 (E-switch-ic) | CHOP | Might have inferior OS |
Chemotherapy
- Carmustine (BCNU) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1 mg/m2 IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
28-day cycle for 6 cycles
References
- Gams RA, Rainey M, Dandy M, Bartolucci AA, Silberman H, Omura G; Southeastern Cancer Study Group. Phase III study of BCOP v CHOP in unfavorable categories of malignant lymphoma: a Southeastern Cancer Study Group trial. J Clin Oncol. 1985 Sep;3(9):1188-95. link to original article contains dosing details in manuscript PubMed
CAP-BOP
CAP-BOP: Cyclophosphamide, Adriamycin (Doxorubicin), Procarbazine, Bleomycin, Oncovin (Vincristine), Prednisone
COP-BLAM: Cyclophosphamide, Oncovin (Vincristine), Prednisone, BLeomycin, Adriamycin (Doxorubicin), Matulane (Procarbazine),
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Laurence et al. 1982 | 1977-1981 | Phase 2 |
Boyd et al. 1988 | 1981-1984 | Phase 2 |
Armitage et al. 1986 | 1982-1984 | Phase 2 |
Vose et al. 1988 | 1982-1986 | Phase 2 |
Chemotherapy
- Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Procarbazine (Matulane) 100 mg/m2 PO once per day on days 1 to 7
- Bleomycin (Blenoxane) 10 units SC once on day 15
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 15
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 15 to 21
21- to 28-day cycle for up to 9 cycles
References
- Laurence J, Coleman M, Allen SL, Silver RT, Pasmantier M. Combination chemotherapy of advanced diffuse histiocytic lymphoma with the six-drug COP-BLAM regimen. Ann Intern Med. 1982 Aug;97(2):190-5. link to original article PubMed
- Armitage JO, Weisenburger DD, Hutchins M, Moravec DF, Dowling M, Sorensen S, Mailliard J, Okerbloom J, Johnson PS, Howe D, Bascom GK, Casey J, Linder J, Purtilo DT. Chemotherapy for diffuse large-cell lymphoma--rapidly responding patients have more durable remissions. J Clin Oncol. 1986 Feb;4(2):160-4. link to original article PubMed
- Boyd DB, Coleman M, Papish SW, Topilow A, Kopel SK, Bernhardt B, Files JC, Schwartz S, Gaynor M, McDermott D, Reisman AM, Coleman BL. COPBLAM III: infusional combination chemotherapy for diffuse large-cell lymphoma. J Clin Oncol. 1988 Mar;6(3):425-33. link to original article PubMed
- Vose JM, Armitage JO, Weisenburger DD, Bierman PJ, Sorensen S, Hutchins M, Moravec DF, Howe D, Dowling MD, Mailliard J, Johnson PS, Pevnick W, Packard WM, Okerbloom J, Thompson RF, Langdon RM Jr, Soori G, Peterson C. The importance of age in survival of patients treated with chemotherapy for aggressive non-Hodgkin's lymphoma. J Clin Oncol. 1988 Dec;6(12):1838-44. link to original article contains dosing details in manuscript PubMed
CCOP
CCOP: Cyclophosphamide, Caelyx (Pegylated liposomal doxorubicin), Oncovin (Vincristine), Prednisone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Martino et al. 2002 | 1998-2000 | Phase 2 |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 30 minutes once on day 1
- Pegylated liposomal doxorubicin (Doxil) 30 mg/m2 IV over 60 minutes once on day 1
- Vincristine (Oncovin) 2 mg IV over 15 minutes once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
21-day cycle for 6 to 8 cycles
References
- Martino R, Perea G, Caballero MD, Mateos MV, Ribera JM, de Oteyza JP, Arranz R, Terol MJ, Sierra J, San Miguel JF. Cyclophosphamide, pegylated liposomal doxorubicin (Caelyx), vincristine and prednisone (CCOP) in elderly patients with diffuse large B-cell lymphoma: results from a prospective phase II study. Haematologica. 2002 Aug;87(8):822-7. link to original article contains dosing details in manuscript PubMed
CEEP
CEEP: Cyclophosphamide, Epirubicin, Eldesine (Vindesine), Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Milpied et al. 2004 (GOELAMS 072) | 1994-1999 | Phase 3 (E-esc) | CHOP | Seems to have superior EFS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Vindesine (Eldisine) 3 mg/m2 IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 80 mg/m2 PO or IV once per day on days 1 to 5
CNS therapy, prophylaxis
- Methotrexate (MTX) 15 mg IT once on day 2
- Methylprednisolone (Solumedrol) IT once on day 2
14-day cycle for 2 cycles
Subsequent treatment
- GOELAMS 072, patients with at least PR: CYM consolidation, then BEAM with auto HSCT intensification
References
- GOELAMS 072: Milpied N, Deconinck E, Gaillard F, Delwail V, Foussard C, Berthou C, Gressin R, Lucas V, Colombat P, Harousseau JL; Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang. Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. N Engl J Med. 2004 Mar 25;350(13):1287-95. link to original article contains dosing details in manuscript PubMed
CEOP
CEOP: Cyclophosphamide, Epirubicin, Oncovin (Vincristine), Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Economopoulos et al. 2002 | 1993-1999 | Phase 3 (C) | CNOP | Did not meet efficacy endpoints |
Chamorey et al. 2005 | 1994-1998 | Phase 3 (C) | MEMID | Did not meet primary endpoint of OS |
Economopoulos et al. 2007 (HE22A99) | 1999-2005 | Phase 3 (C) | CEOP-14 | Did not meet primary endpoint of OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Epirubicin (Ellence) 70 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg PO once per day on days 1 to 7
21-day cycles
References
- Economopoulos T, Dimopoulos MA, Mellou S, Pavlidis N, Samantas E, Nicolaides C, Tsatalas C, Papadopoulos A, Papageogriou E, Papasavvas P, Fountzilas G. Treatment of intermediate- and high-grade non-Hodgkin's lymphoma using CEOP versus CNOP. Eur J Haematol. 2002 Mar;68(3):135-43. link to original article contains dosing details in manuscript PubMed
- Chamorey E, Gressin R, Peyrade F, Rossi JF, Lepeu G, Foussard C, Harrousseau JL, Fabbro M, Richard B, Delwail V, Maisonneuve H, Vilque JP, Thyss A. Prospective randomized study comparing MEMID with a chop-like regimen in elderly patients with aggressive non-Hodgkin's lymphoma. Oncology. 2005;69(1):19-26. Epub 2005 Jul 28. link to original article PubMed
- HE22A99: Economopoulos T, Psyrri A, Dimopoulos MA, Kalogera-Fountzila A, Pavlidis N, Tsatalas C, Nikolaides C, Mellou S, Xiros N, Fountzilas G; Hellenic Cooperative Oncology Group. CEOP-21 versus CEOP-14 chemotherapy with or without rituximab for the first-line treatment of patients with aggressive lymphomas: results of the HE22A99 trial of the Hellenic Cooperative Oncology Group. Cancer J. 2007 Sep-Oct;13(5):327-34. link to original article PubMed
CEOP (Prednisolone)
CEOP: Cyclophosphamide, Epirubicin, Oncovin (Vincristine), Prednisolone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hertzberg et al. 2014 (ALLG NHL07) | 1994-1999 | Phase 3 (C) | DI-CEOP | Did not meet primary endpoint of OS60 |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
Glucocorticoid therapy
- Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
21-day cycle for 6 cycles
References
- ALLG NHL07: Hertzberg M, Matthews JP, Stone JM, Dubosq MC, Grigg A, Ellis D, Benson W, Browett P, Horvath N, Januszewicz H, Abdi E, Green M, Bonaventura A, Marlton P, Cannell P, Wolf M; ALLG. A phase III randomized trial of high-dose CEOP + filgrastim versus standard-dose CEOP in patients with non-Hodgkin lymphoma: 10-year follow-up data: Australasian Leukaemia and Lymphoma Group (ALLG) NHL07 trial. Am J Hematol. 2014 May;89(5):536-41. Epub 2014 Feb 21. link to original article contains dosing details in abstract PubMed
CHOEP-14
CHOEP-14: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone every 14 days
CHOPE: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne, Etoposide
VACOP: Vepesid (Etoposide), Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Pfreundschuh et al. 2004 (NHL-B1) | 1993-2000 | Phase 3 (E-esc) | 1. CHOP-21 2. CHOP-14 |
Superior EFS | Seems more toxic |
3. CHOEP-21 | Seems to have superior OS | ||||
Pfreundschuh et al. 2004 (NHL-B2) | 1993-2000 | Phase 3 (E-esc) | 1. CHOEP-21 2. CHOP-21 3. CHOP-14 |
Did not meet primary endpoint of EFS | Seems more toxic |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive therapy
- Filgrastim (Neupogen) by the following weight-based criteria:
- Less than 75 kg: 300 mcg SC once per day on days 4 to 13
- 75 kg or more: 480 mcg SC once per day on days 4 to 13
14-day cycle for 6 cycles; next cycle to start as long as WBC count is greater than 2.5 x 109/L and platelets greater than 80 x 109/L
Subsequent treatment
- NHL-B1, patients with initial bulky disease (mass conglomerate at least 7.5 cm) received: RT consolidation x 3600 cGy to extranodal sites of disease when possible
References
- NHL-B1: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article contains dosing details in manuscript PubMed
- NHL-B2: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. link to original article contains dosing details in manuscript PubMed
- Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains dosing details in manuscript PubMed
- Update: Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. Epub 2011 Sep 21. link to original article contains dosing details in abstract PubMed
CHOEP-21
CHOEP-21: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone every 21 days
CHOPE: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne, Etoposide
VACOP: Vepesid (Etoposide), Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Köppler et al. 1991 | NR | Phase 3 (C) | hCHOP/IVEP | ||
Kaiser et al. 2002 | 1990-1997 | Phase 3 (C) | CHOEP, then BEAM with auto HSCT | Did not meet primary endpoint of OS | |
Pfreundschuh et al. 2004 (NHL-B1) | 1993-2000 | Phase 3 (E-esc) | 1. CHOP-21 2. CHOP-14 |
Superior EFS | Seems more toxic |
3. CHOEP-14 | Seems to have inferior OS | ||||
Pfreundschuh et al. 2004 (NHL-B2) | 1993-2000 | Phase 3 (E-esc) | 1. CHOEP-14 2. CHOP-21 3. CHOP-14 |
Did not meet primary endpoint of EFS | Seems more toxic |
Pfreundschuh et al. 2007 (DSHNHL-1999-2) | 2000-2003 | Phase 3 (C) | High CHOEP-21 | Did not meet primary endpoint of EFS36 | Less toxic |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive therapy
- Filgrastim (Neupogen) by discretion of ordering physician
21-day cycle for 4 to 6 cycles; next cycle to start as long as WBC is >2.5 and platelets >80
Subsequent treatment
- NHL-B1, patients with initial bulky disease (mass conglomerate at least 7.5 cm) received: RT consolidation x 3600 cGy to extranodal sites of disease when possible
References
- Köppler H, Pflüger KH, Eschenbach I, Pfab R, Birkmann J, Zeller W, Steinhauer EU, Gropp C, Oehl S, Lötzke E, Kuhn H, Drings P, Gossmann HH, Lennert K, Stein H, Havemann K. Sequential versus alternating chemotherapy for high grade non-Hodgkin's lymphomas: a randomized multicentre trial. Hematol Oncol. 1991 Jul-Oct;9(4-5):217-23. link to original article PubMed
- Kaiser U, Uebelacker I, Abel U, Birkmann J, Trümper L, Schmalenberg H, Karakas T, Metzner B, Hossfeld DK, Bischoff HG, Franke A, Reiser M, Müller P, Mantovani L, Grundeis M, Rothmann F, von Seydewitz CU, Mesters RM, Steinhauer EU, Krahl D, Schumacher K, Kneba M, Baudis M, Schmitz N, Pfab R, Köppler H, Parwaresch R, Pfreundschuh M, Havemann K. Randomized study to evaluate the use of high-dose therapy as part of primary treatment for "aggressive" lymphoma. J Clin Oncol. 2002 Nov 15;20(22):4413-9. link to original article PubMed
- NHL-B1: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article contains dosing details in manuscript PubMed
- NHL-B2: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. link to original article contains dosing details in manuscript PubMed
- Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains dosing details in manuscript PubMed
- Update: Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. Epub 2011 Sep 21. link to original article contains dosing details in abstract PubMed
- DSHNHL-1999-2: Pfreundschuh M, Zwick C, Zeynalova S, Dührsen U, Pflüger KH, Vrieling T, Mesters R, Mergenthaler HG, Einsele H, Bentz M, Lengfelder E, Trümper L, Rübe C, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: II - Results of the randomized high-CHOEP trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Ann Oncol. 2008 Mar;19(3):545-52. Epub 2007 Dec 6. link to original article contains dosing details in manuscript PubMed NCT00053768
CHOP
CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Regimen variant #1, 3 cycles, prednisone 40 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Link et al. 1990 | 1983-1987 | Phase 3 (E-de-esc) | CHOP & RT | Did not meet primary endpoint of DFS |
Note: this was a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Note some substantial differences from typical CHOP protocols.
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.5 mg/m2 IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) as follows:
- Cycle 1: 40 mg/m2 PO once per day on days 1 to 21
- Cycle 2: 40 mg/m2 PO once per day on days 1 to 7
- Cycle 3: 40 mg/m2 PO once per day on days 1 to 5
21-day cycle for 3 cycles
Subsequent treatment
- 6-MP & MTX maintenance
Regimen variant #2, 3 cycles, prednisone 100 mg
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Miller et al. 1998 (SWOG S8736) | 1988-1995 | Phase 3 (E-switch-ooc) | See link | See link |
Reyes et al. 2005 (LNH 93-01) | 1993-2000 | Phase 3 (C) | ACVBP | Inferior OS |
Persky et al. 2014 (SWOG S0313) | 2004-2008 | Phase 2 |
Note: this was a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV over 1 to 2 minutes once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV over 1 to 2 minutes once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 3 cycles
Subsequent treatment
- SWOG S0313: IFRT, then ibritumomab tiuxetan consolidation
- SWOG S8736 & LNH 93-01: IFRT consolidation, 180 to 200 cGy fractions, total dose of 4000 to 5500 cGy. Total dose was often influenced by whether patients had clinical evidence of residual disease after 4000 cGy.
Regimen variant #3, 4 cycles
Study | Dates of enrollment | Evidence |
---|---|---|
Tondini et al. 1993 | 1985-1990 | Phase 2 |
Bonnet et al. 2007 | 1993-2002 | Non-randomized part of RCT |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
21-day cycle for 4 cycles
Subsequent treatment
- Bonnet et al. 2007: IFRT consolidation x 4000 cGy versus no further treatment
Regimen variant #4, 6 cycles, 100 mg prednisone
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pfreundschuh et al. 2004 (NHL-B1) | 1993-2000 | Phase 3 (C) | 1. CHOEP-14 2. CHOP-14 |
Seems to have inferior OS |
3. CHOEP-21 | Inferior EFS | |||
Pfreundschuh et al. 2004 (NHL-B2) | 1993-2000 | Phase 3 (C) | 1. CHOEP-14 | Did not meet primary endpoint of EFS |
2. CHOEP-21 | Did not meet primary endpoint of EFS | |||
3. CHOP-14 | Inferior OS | |||
Verdonck et al. 2007 (HOVON-26) | 1994-2004 | Phase 3 (C) | I-CHOP | Did not meet primary endpoint of OS |
Fridrik et al. 2009 (AGMT NHL-5) | 1995-2001 | Phase 3 (C) | CEOP/IMVP-Dexa | Inferior OS |
Preceding treatment
- NHL-B1 and NHL-B2: Vincristine & Prednisone pre-phase
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive therapy
- Per NHL-B1 and NHL-B2: At the discretion of ordering physician: Filgrastim (Neupogen) by the following weight-based criteria:
- Less than 75 kg: 300 mcg SC once per day on days 4 to 13
- 75 kg or more: 480 mcg SC once per day on days 4 to 13
21-day cycle for 6 cycles
Subsequent treatment
- NHL-B2, patients with "lymphoma masses or conglomerates with a diameter ≥7.5 cm) or extranodal involvement": RT consolidation x 3600 cGy to areas of initial bulky disease
Regimen variant #5, 6 cycles, 50 mg/m2 prednisone
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sonneveld et al. 1995 | 1988-1993 | Phase 3 (C) | CNOP | Seems to have superior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 50 mg/m2 PO once per day on days 1 to 5
28-day cycle for 6 cycles
Regimen variant #6, 6 to 8 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zinzani et al. 1995 | 1991-1993 | Phase 3 (C) | CIOP | Did not meet efficacy endpoints |
Habermann et al. 2006 (ECOG E4494) | 1998-2001 | Phase 3 (C) | R-CHOP | Seems to have inferior FFS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
Supportive therapy
- Filgrastim (Neupogen) "recommended according to guidelines"
21-day cycle for 6 to 8 cycles
Subsequent treatment
- ECOG E4494, patients with CR/PR: Rituximab maintenance versus observation
Regimen variant #7, 8 cycles, 40 mg/m2 prednisone
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tilly et al. 2003 | 1993-1998 | Phase 3 (C) | ACVBP | Seems to have inferior OS |
Coiffier et al. 2002 (LNH 98-5) | 1998-2000 | Phase 3 (C) | R-CHOP | Inferior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
Supportive therapy
- Filgrastim (Neupogen) used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
21-day cycle for 8 cycles
Regimen variant #8, 8 cycles, 100 mg prednisone
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
McKelvey et al. 1976 | 1972-1974 | Phase 3 (E-esc) | HOP | Did not meet endpoint of OS |
Elias et al. 1978 | 1974-1977 | Non-randomized | ||
Gordon et al. 1992 | 1984-1988 | Phase 3 (C) | m-BACOD | Did not meet endpoint of OS |
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) | 1986-1991 | Phase 3 (C) | 1. MACOP-B | Did not meet endpoint of OS |
2. m-BACOD | Did not meet endpoint of OS | |||
3. ProMACE-CytaBOM | Did not meet endpoint of OS | |||
Verdonck et al. 1995 | 1987-1994 | Phase 3 (C) | CHOP x 3, then HDT with auto HSCT | Did not meet primary endpoint of EFS |
Miller et al. 1998 (SWOG S8736) | 1988-1995 | Phase 3 (C) | CHOP x 3, then RT | Seems to have inferior OS |
Jerkeman et al. 1999 | 1989-1994 | Phase 3 (C) | MACOP-B | Did not meet primary endpoint of OS |
Betticher et al. 2006 (MISTRAL) | 1997-2003 | Phase 3 (C) | SHiDo | Did not meet primary endpoint of OS |
Ohmachi et al. 2010 (JCOG 9809) | 1999-2002 | Phase 3 (C) | CHOP-14 | Did not meet primary endpoint of PFS |
Note: McKelvey et al. 1976 gave CHOP for 3 cycles past CR.
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV over 1 to 2 minutes once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV over 1 to 2 minutes once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 8 cycles
Regimen variant #9, 8 cycles, uncapped vincristine, 100 mg prednisone
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gams et al. 1985 | 1977-1981 | Phase 3 (E-switch-ic) | BCOP | Might have superior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1 mg/m2 IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 8 cycles
Regimen variant #10, 8 cycles, uncapped vincristine, 100 mg/m2 prednisone
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Milpied et al. 2004 (GOELAMS 072) | 1994-1999 | Phase 3 (C) | CEEP, then CYM, then BEAM with auto HSCT | Seems to have inferior EFS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
21-day cycle for 8 cycles
Regimen variant #11, other
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Andersen et al. 1990 | 1983-1985 | Phase 3 (C) | CisEBP | Superior CR rate |
Chemotherapy
Glucocorticoid therapy
References
- McKelvey EM, Gottlieb JA, Wilson HE, Haut A, Talley RW, Stephens R, Lane M, Gamble JF, Jones SE, Grozea PN, Gutterman J, Coltman C, Moon TE. Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976 Oct;38(4):1484-93. link to original article contains dosing details in manuscript PubMed
- Elias L, Portlock CS, Rosenberg SA. Combination chemotherapy of diffuse histiocytic lymphoma with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP). Cancer. 1978 Oct;42(4):1705-10. link to original article contains dosing details in manuscript PubMed
- Gams RA, Rainey M, Dandy M, Bartolucci AA, Silberman H, Omura G; Southeastern Cancer Study Group. Phase III study of BCOP v CHOP in unfavorable categories of malignant lymphoma: a Southeastern Cancer Study Group trial. J Clin Oncol. 1985 Sep;3(9):1188-95. link to original article PubMed
- Link MP, Donaldson SS, Berard CW, Shuster JJ, Murphy SB; POG. Results of treatment of childhood localized non-Hodgkin's lymphoma with combination chemotherapy with or without radiotherapy. N Engl J Med. 1990 Apr 26;322(17):1169-74. link to original article contains dosing details in manuscript PubMed
- Andersen J, Thorling K, Bentzen SM, Brincker H, Christensen BE, Pedersen M; Danish Lymphoma Study Group. Phase III trial of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) versus cisplatin, etoposide, bleomycin and prednisone (CisEBP) for the treatment of advanced non-Hodgkin's lymphoma of high grade malignancy. Acta Oncol. 1990;29(8):995-9. link to original article PubMed
- Pavlovsky S, Santarelli MT, Erazo A, Diaz Maqueo JC, Somoza N, Lluesma Goñalons M, Cervantes G, Garcia Vela EL, Corrado C, Magnasco H, Milone G. Results of a randomized study of previously-untreated intermediate and high grade lymphoma using CHOP versus CNOP. Ann Oncol. 1992 Mar;3(3):205-9. link to original article PubMed
- Gordon LI, Harrington D, Andersen J, Colgan J, Glick J, Neiman R, Mann R, Resnick GD, Barcos M, Gottlieb A, O'Connell M. Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma. N Engl J Med. 1992 Nov 5;327(19):1342-9. link to original article contains dosing details in manuscript PubMed
- SWOG-8516/Intergroup 0067: Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. link to original article PubMed
- Update: Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group. J Clin Oncol. 2009 Jan 1;27(1):114-9. Epub 2008 Dec 1. link to original article link to PMC article PubMed
- Tondini C, Zanini M, Lombardi F, Bengala C, Rocca A, Giardini R, Buzzoni R, Valagussa P, Bonadonna G. Combined modality treatment with primary CHOP chemotherapy followed by locoregional irradiation in stage I or II histologically aggressive non-Hodgkin's lymphomas. J Clin Oncol. 1993 Apr;11(4):720-5. link to original article PubMed
- Verdonck LF, van Putten WL, Hagenbeek A, Schouten HC, Sonneveld P, van Imhoff GW, Kluin-Nelemans HC, Raemaekers JM, van Oers RH, Haak HL, Schots R, Dekker AW, de Gast GC, Löwenberg B. Comparison of CHOP chemotherapy with autologous bone marrow transplantation for slowly responding patients with aggressive non-Hodgkin's lymphoma. N Engl J Med. 1995 Apr 20;332(16):1045-51. link to original article contains dosing details in manuscript PubMed
- Zinzani PL, Martelli M, Storti S, Musso M, Cantonetti M, Leone G, Cajozzo A, Papa G, Iannitto E, Perrotti A, Bendandi M, Gherlinzoni F, Gentilini P, Rossi G, Aitini E, Mandelli F, Tura S. Phase III comparative trial using CHOP vs CIOP in the treatment of advanced intermediate-grade non-Hodgkin's lymphoma. Leuk Lymphoma. 1995 Oct;19(3-4):329-35. link to original article PubMed
- Sonneveld P, de Ridder M, van der Lelie H, Nieuwenhuis K, Schouten H, Mulder A, van Reijswoud I, Hop W, Lowenberg B. Comparison of doxorubicin and mitoxantrone in the treatment of elderly patients with advanced diffuse non-Hodgkin's lymphoma using CHOP versus CNOP chemotherapy. J Clin Oncol. 1995 Oct;13(10):2530-9. link to original article contains dosing details in manuscript PubMed
- SWOG S8736: Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med. 1998 Jul 2;339(1):21-6. link to original article contains dosing details in manuscript PubMed NCT00005089
- Update: Stephens DM, Li H, LeBlanc ML, Puvvada SD, Persky D, Friedberg JW, Smith SM. Continued risk of relapse independent of treatment modality in limited-stage diffuse large B-cell lymphoma: Final and long-term analysis of Southwest Oncology Group study S8736. J Clin Oncol. 2016 Sep 1;34(25):2997-3004. Epub 2016 Jul 5. link to original article link to PMC article PubMed
- Jerkeman M, Anderson H, Cavallin-Ståhl E, Dictor M, Hagberg H, Johnson A, Kaasa S, Kvaløy S, Sundström C, Akerman M; Nordic Lymphoma Group. CHOP versus MACOP-B in aggressive lymphoma--a Nordic Lymphoma Group randomised trial. Ann Oncol. 1999 Sep;10(9):1079-86. link to original article does not contain dosing details PubMed
- LNH 98-5: Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C; Groupe d'Etude des Lymphomes de l'Adulte. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. link to original article contains dosing details in manuscript PubMed
- Update: Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. Epub 2005 May 2. link to original article contains dosing details in abstract PubMed
- Update: Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010 Sep 23;116(12):2040-5. Epub 2010 Jun 14. link to original article contains dosing details in manuscript link to PMC article PubMed
- Update: Mounier N, Heutte N, Thieblemont C, Briere J, Gaulard P, Feugier P, Ghesquieres H, Van Den Neste E, Robu D, Tilly H, Bouabdallah R, Safar V, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte. Ten-year relative survival and causes of death in elderly patients treated with R-CHOP or CHOP in the GELA LNH-985 trial. Clin Lymphoma Myeloma Leuk. 2012 Jun;12(3):151-4. Epub 2012 Feb 1. link to original article PubMed
- Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003 Dec 15;102(13):4284-9. Epub 2003 Aug 14. link to original article contains dosing details in manuscript PubMed
- NHL-B1: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article contains dosing details in manuscript PubMed
- NHL-B2: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. link to original article contains dosing details in manuscript PubMed
- GOELAMS 072: Milpied N, Deconinck E, Gaillard F, Delwail V, Foussard C, Berthou C, Gressin R, Lucas V, Colombat P, Harousseau JL; Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang. Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. N Engl J Med. 2004 Mar 25;350(13):1287-95. link to original article contains dosing details in manuscript PubMed
- ECOG E1484: Horning SJ, Weller E, Kim K, Earle JD, O'Connell MJ, Habermann TM, Glick JH. Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol. 2004 Aug 1;22(15):3032-8. Epub 2004 Jun 21. link to original article PubMed
- LNH 93-01: Reyes F, Lepage E, Ganem G, Molina TJ, Brice P, Coiffier B, Morel P, Ferme C, Bosly A, Lederlin P, Laurent G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med. 2005 Mar 24;352(12):1197-205. link to original article PubMed
- Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains dosing details in manuscript PubMed
- Update: Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. Epub 2011 Sep 21. link to original article contains dosing details in abstract PubMed
- ECOG E4494: Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. link to original article contains dosing details in manuscript PubMed NCT00003150
- MISTRAL: Betticher DC, Martinelli G, Radford JA, Kaufmann M, Dyer MJ, Kaiser U, Aulitzky WE, Beck J, von Rohr A, Kovascovics T, Cogliatti SB, Cina S, Maibach R, Cerny T, Linch DC. Sequential high dose chemotherapy as initial treatment for aggressive sub-types of non-Hodgkin lymphoma: results of the international randomized phase III trial (MISTRAL). Ann Oncol. 2006 Oct;17(10):1546-52. Epub 2006 Aug 3. link to original article PubMed NCT00003215
- Bonnet C, Fillet G, Mounier N, Ganem G, Molina TJ, Thiéblemont C, Fermé C, Quesnel B, Martin C, Gisselbrecht C, Tilly H, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2007 Mar 1;25(7):787-92. Epub 2007 Jan 16. link to original article contains dosing details in manuscript PubMed
- HOVON-26: Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, Ossenkoppele GJ, Doorduijn JK, Sonneveld P, van Imhoff GW. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007 Apr 1;109(7):2759-66. link to original article contains dosing details in manuscript PubMed
- AGMT NHL-5: Fridrik MA, Hausmaninger H, Lang A, Drach J, Krieger O, Geissler D, Michlmayr G, Ulsperger E, Chott A, Oberaigner W, Greil R. Dose-dense therapy improves survival in aggressive non-Hodgkin's lymphoma. Ann Hematol. 2010 Mar;89(3):273-82. Epub 2009 Aug 20. link to original article PubMed
- JCOG 9809: Ohmachi K, Tobinai K, Kobayashi Y, Itoh K, Nakata M, Shibata T, Morishima Y, Ogura M, Suzuki T, Ueda R, Aikawa K, Nakamura S, Fukuda H, Shimoyama M, Hotta T; Lymphoma Study Group of the Japan Clinical Oncology Group. Phase III trial of CHOP-21 versus CHOP-14 for aggressive non-Hodgkin's lymphoma: final results of the Japan Clinical Oncology Group Study, JCOG 9809. Ann Oncol. 2011 Jun;22(6):1382-91. Epub 2010 Dec 31. link to original article contains dosing details in manuscript PubMed NCT00133302
- SWOG S0313: Persky DO, Miller TP, Unger JM, Spier CM, Puvvada S, Stea BD, Press OW, Constine LS, Barton KP, Friedberg JW, LeBlanc M, Fisher RI. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood. 2015 Jan 8;125(2):236-41. Epub 2014 Nov 13. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00070018
CHOP (Prednisolone)
CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burton et al. 2006 (BNLI CHOPVPMITCEBO-GOODRISK) | 1997-1999 | Phase 3 (C) | PMitCEBO | Did not meet primary endpoint of FFS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
Glucocorticoid therapy
- Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
21-day cycle for 6 to 8 cycles
References
- BNLI CHOPVPMITCEBO-GOODRISK: Burton C, Linch D, Hoskin P, Milligan D, Dyer MJ, Hancock B, Mouncey P, Smith P, Qian W, MacLennan K, Jack A, Webb A, Cunningham D. A phase III trial comparing CHOP to PMitCEBO with or without G-CSF in patients aged 60 plus with aggressive non-Hodgkin's lymphoma. Br J Cancer. 2006 Mar 27;94(6):806-13. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00005867
CHOP-14
CHOP-DI: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Dose Intense
I-CHOP: Intensified Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
CHOP-14: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone every 14 days
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Blayney et al. 2003 (SWOG 9349) | 1994-1997 | Phase 2 |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 65 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive therapy
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 2 to 11, or until ANC is greater than 10,000/μL
14-day cycle for up to 6 cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Verdonck et al. 2007 (HOVON-26) | 1994-2004 | Phase 3 (E-esc) | CHOP-21 | Did not meet primary endpoint of OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 70 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive therapy
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 2 to 11
14-day cycle for 6 cycles
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pfreundschuh et al. 2004 (NHL-B1) | 1993-2000 | Phase 3 (E-esc) | 1. CHOEP-14 | Inferior EFS |
2. CHOEP-21 3. CHOP-21 |
Seems to have superior OS | |||
Pfreundschuh et al. 2008 (RICOVER-60) | 2000-2005 | Phase 3 (C) | 1. CHOP-14 x 8 | Seems to have inferior EFS |
2. R-CHOP-14 x 6 | Inferior OS | |||
3. R-CHOP-14 x 8 | Inferior PFS |
Preceding treatment
- Vincristine & Prednisone pre-phase (recommended in NHL-B1 and mandatory in RICOVER-60)
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive therapy
- (per Pfreundschuh et al. 2004):
- Filgrastim (Neupogen) by the following weight-based criteria:
- Less than 75 kg: 300 mcg SC once per day on days 4 to 13
- 75 kg or more: 480 mcg SC once per day on days 4 to 13
14-day cycle for 6 cycles
Subsequent treatment
- RICOVER-60, patients with "Initial bulky disease" (lymphoma masses or conglomerates with a diameter of at least 7.5 cm or extranodal involvement): RT consolidation x 3600 cGy to areas of initial bulky disease
Regimen variant #4
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pfreundschuh et al. 2008 (RICOVER-60) | 2000-2005 | Phase 3 (E-esc) | 1. CHOP-14 x 6 | Seems to have superior EFS |
2. R-CHOP-14 x 6 | Not reported | |||
3. R-CHOP-14 x 8 | Not reported |
Preceding treatment
- Vincristine & Prednisone pre-phase
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive therapy
- Filgrastim (Neupogen) by the following weight-based criteria:
- Less than 75 kg: 300 mcg SC once per day on days 4 to 13
- 75 kg or more: 480 mcg SC once per day on days 4 to 13
14-day cycle for 8 cycles
Subsequent treatment
- RICOVER-60, patients with "Initial bulky disease" (lymphoma masses or conglomerates with a diameter of at least 7.5 cm or extranodal involvement): RT consolidation x 3600 cGy to areas of initial bulky disease
References
- SWOG 9349: Blayney DW, LeBlanc ML, Grogan T, Gaynor ER, Chapman RA, Spiridonidis CH, Taylor SA, Bearman SI, Miller TP, Fisher RI; SWOG. Dose-intense chemotherapy every 2 weeks with dose-intense cyclophosphamide, doxorubicin, vincristine, and prednisone may improve survival in intermediate- and high-grade lymphoma: a phase II study of the Southwest Oncology Group (SWOG 9349). J Clin Oncol. 2003 Jul 1;21(13):2466-73. link to original article contains dosing details in manuscript PubMed
- NHL-B1: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article contains dosing details in manuscript PubMed
- NHL-B2: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. link to original article PubMed
- HOVON-26: Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, Ossenkoppele GJ, Doorduijn JK, Sonneveld P, van Imhoff GW. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007 Apr 1;109(7):2759-66. link to original article contains dosing details in manuscript PubMed
- RICOVER-60: Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. Epub 2008 Jan 15. link to original article contains dosing details in manuscript PubMed NCT00052936
CHOP Modified
mCHOP: modified Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Link et al. 1997 | 1983-1991 | Non-randomized part of RCT |
Note: This regimen has some major differences from standard CHOP.
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once per day on days 1, 22, 43
- Doxorubicin (Adriamycin) 40 mg/m2 IV once per day on days 1, 22, 43
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36, 43
Glucocorticoid therapy
- Prednisone (Sterapred) 40 mg/m2/day on days 1 to 28, 43 to 47
9-week course
References
- Link MP, Shuster JJ, Donaldson SS, Berard CW, Murphy SB. Treatment of children and young adults with early-stage non-Hodgkin's lymphoma. N Engl J Med. 1997 Oct 30;337(18):1259-66. link to original article PubMed
CHOP Modified (Prednisolone)
mCHOP: modified Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bessell et al. 2003 (CLG NH 3003) | 1993-2000 | Phase 3 (E-switch-ic) | MCOP | Not designed to look at efficacy |
Note: This regimen was designed for elderly patients and is of lower intensity than standard CHOP.
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 30 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1 mg IV once on day 1
Glucocorticoid therapy
- Prednisolone (Millipred) 20 mg PO twice per day on days 1 to 5
21-day cycle for 6 cycles
References
- CLG NH 3003: Bessell EM, Burton A, Haynes AP, Glaholm J, Child JA, Cullen MH, Davies JM, Smith GM, Ellis IO, Jack A, Jones EL; Central Lymphoma Group UK. A randomised multicentre trial of modified CHOP versus MCOP in patients aged 65 years and over with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003 Feb;14(2):258-67. link to original article contains dosing details in manuscript PubMed NCT00002576
CHOP-BCG
CHOP-BCG: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Bacillus Calmette-Guérin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Jones et al. 1979 | 1974-1977 | Phase 3 (E-esc) | 1. CHOP-B | Not reported |
2. COP-Bleo | Might have superior CR rate |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/mg2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/mg2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/mg2 (maximum dose of 2 mg) IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Immunotherapy
- BCG vaccine 1 ampule SC once per day on days 8 & 15
21- to 28-day cycle for 8 cycles
References
- Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Butler JJ, Byrne GE Jr, Moon TE, Fisher R, Haskins CL, Coltman CA Jr; SWOG. Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study. Cancer. 1979 Feb;43(2):417-25. link to original article contains dosing details in manuscript PubMed
- Update: Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Talley R, Butler JJ, Byrne GE Jr, Hartsock R, Dixon D, Salmon SE. Improved complete remission rates and survival for patients with large cell lymphoma treated with chemoimmunotherapy: a Southwest Oncology Group Study. Cancer. 1983 Mar 15;51(6):1083-90. link to original article PubMed
CHOP-B
CHOP-B: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Bleomycin
B-CHOP: Bleomycin, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
BACOP: Bleomycin, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rodriguez et al. 1977 | 1973-1975 | Phase 2 | ||
Skarin et al. 1977 | 1973-1975 | Phase 2 | ||
Jones et al. 1979 | 1974-1977 | Phase 3 (E-esc) | 1. CHOP-BCG | Not reported |
2. COP-Bleo | Might have superior CR rate | |||
Newcomer et al. 1982 | NR in abstract | Randomized, fewer than 20 patients (E-de-esc) | ACOMLA | Seems to have superior RFS |
Bajetta et al. 1988 | 1976-1984 | Phase 3 (E-esc) | CVP | Seems to have superior FFFP |
Meyer et al. 1993 | 1982-1989 | Phase 3 (C) | esc-BACOP | Did not meet efficacy endpoints |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Bleomycin (Blenoxane) 4 mg/m2 IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 8 cycles
References
- Rodriguez V, Cabanillas F, Burgess MA, McKelvey EM, Valdivieso M, Bodey GP, Freireich EJ. Combination chemotherapy ("CHOP-Bleo") in advanced (non-Hodgkin) malignant lymphoma. Blood. 1977 Mar;49(3):325-33. link to original article PubMed
- Skarin AT, Rosenthal DS, Moloney WC, Frei E 3rd. Combination chemotherapy of advanced non-Hodgkin lymphoma with bleomycin, adriamycin, cyclophosphamide, vincristine, and prednisone (BACOP). Blood. 1977 May;49(5):759-70. link to original article PubMed
- Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Butler JJ, Byrne GE Jr, Moon TE, Fisher R, Haskins CL, Coltman CA Jr; SWOG. Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study. Cancer. 1979 Feb;43(2):417-25. link to original article contains dosing details in manuscript PubMed
- Update: Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Talley R, Butler JJ, Byrne GE Jr, Hartsock R, Dixon D, Salmon SE. Improved complete remission rates and survival for patients with large cell lymphoma treated with chemoimmunotherapy: a Southwest Oncology Group Study. Cancer. 1983 Mar 15;51(6):1083-90. link to original article PubMed
- Newcomer LN, Cadman EC, Nerenberg MI, Chen M, Bertino JR, Farber LR, Prosnitz LR. Randomized study comparing doxorubicin, cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (ACOMLA) with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-B) in the treatment of diffuse histiocytic lymphoma. Cancer Treat Rep. 1982 Jun;66(6):1279-84. PubMed
- Bajetta E, Valagussa P, Bonadonna G, Lattuada A, Buzzoni R, Rilke F, Banfi A. Combined modality treatment for stage I-II non-Hodgkin's lymphomas: CVP versus BACOP chemotherapy. Int J Radiat Oncol Biol Phys. 1988 Jul;15(1):3-12. link to original article PubMed
- Meyer RM, Quirt IC, Skillings JR, Cripps MC, Bramwell VH, Weinerman BH, Gospodarowicz MK, Burns BF, Sargeant AM, Shepherd LE, Zee B, Hryniuk WM. Escalated as compared with standard doses of doxorubicin in BACOP therapy for patients with non-Hodgkin's lymphoma. N Engl J Med. 1993 Dec 9;329(24):1770-6. link to original article PubMed
CHVP
CHVP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vumon (Teniposide), Prednisone
CHVmP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vm26 (Teniposide), Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burgers et al. 1983 (EORTC 20751) | 1975-1980 | Phase 3 (C) | CVP | Not reported |
Carde et al. 1991 | 1980-1986 | Phase 3 (C) | CHVmP-VB | Inferior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Teniposide (Vumon) 60 mg/m2 IV over 60 minutes once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
21- to 28-day cycle for 8 cycles
References
- EORTC 20751: Burgers JM, Somers R, Quasim MM, van Glabbekke M. Report on the EORTC 20751 lymphoma trial. Int J Radiat Oncol Biol Phys. 1983 Jan;9(1):11-5. link to original article PubMed
- Carde P, Meerwaldt JH, van Glabbeke M, Somers R, Monconduit M, Thomas J, de Wolf-Peeters C, de Pauw B, Tanguy A, Kluin-Nelemans JC, Noordijk EM, Regnier R, Bron D, Lustman-Marechal J, Caillou B, Bosq J, van Heerde P, van Unnik JAM, Burgers MV, Hayat M, Cosset JM, van der Schueren E, Wagener J, Hagenbeek A, Cattan A, Duez N, Tubiana M; EORTC Lymphoma Group. Superiority of second over first generation chemotherapy in a randomized trial for stage III-IV intermediate and high-grade non-Hodgkin's lymphoma (NHL): the 1980-1985 EORTC trial. Ann Oncol. 1991 Jun;2(6):431-5. link to original article contains dosing details in abstract PubMed
CHVmP-VB
CHVmP-VB: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vm26 (Teniposide), Prednisone, Vincristine, Bleomycin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Carde et al. 1991 | 1980-1986 | Phase 3 (E-esc) | CHVP | Superior OS |
Somers et al. 1994 (EORTC 20855) | 1986-1991 | Phase 3 (C) | ProMACE-MOPP | Inferior ORR |
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Teniposide (Vumon) 60 mg/m2 IV over 60 minutes once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 15
- Bleomycin (Blenoxane) 10 mg IV once on day 15
Glucocorticoid therapy
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
21-day cycle for 8 cycles
References
- Carde P, Meerwaldt JH, van Glabbeke M, Somers R, Monconduit M, Thomas J, de Wolf-Peeters C, de Pauw B, Tanguy A, Kluin-Nelemans JC, Noordijk EM, Regnier R, Bron D, Lustman-Marechal J, Caillou B, Bosq J, van Heerde P, van Unnik JAM, Burgers MV, Hayat M, Cosset JM, van der Schueren E, Wagener J, Hagenbeek A, Cattan A, Duez N, Tubiana M; EORTC Lymphoma Group. Superiority of second over first generation chemotherapy in a randomized trial for stage III-IV intermediate and high-grade non-Hodgkin's lymphoma (NHL): the 1980-1985 EORTC trial. Ann Oncol. 1991 Jun;2(6):431-5. link to original article contains dosing details in abstract PubMed
- EORTC 20855: Somers R, Carde P, Thomas J, Tirelli U, Keuning JJ, Bron D, Delmer A, de Bock R, De Wolf-Peeters C, van Glabbeke M, Duez N; EORTC. EORTC study of non-Hodgkin's lymphoma: phase III study comparing CHVmP-VB and ProMACE-MOPP in patients with stage II, III, and IV intermediate- and high-grade lymphoma. Ann Oncol. 1994;5 Suppl 2:85-9. Erratum in: Ann Oncol 1994 May;5(5):475. link to original article contains dosing details in manuscript PubMed
C-MOPP
C-MOPP: CyclophosphaMide, Oncovin (Vincristine), Procarbazine, Prednisone
COPP: Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone
Regimen
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
DeVita et al. 1975 | 1965-1972 | Phase 2 | |
Stein et al. 1974 | 1970-1973 | Phase 3 (E-esc) | Vincristine & Prednisone (VP) |
Chemotherapy
- Cyclophosphamide (Cytoxan) 650 mg/m2 IV once per day on days 1 & 8
- Vincristine (Oncovin) 1.4 mg/m2 IV once per day on days 1 & 8
- Procarbazine (Matulane) 100 mg/m2 PO once per day on days 1 to 14
Glucocorticoid therapy
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 14
28-day cycle for 6 cycles
References
- Stein RS, Moran EM, Desser RK, Miller JB, Golomb HM, Ultmann JE. Combination chemotherapy of lymphomas other than Hodgkin's disease. Ann Intern Med. 1974 Nov;81(5):601-8. link to original article PubMed
- DeVita VT Jr, Canellos GP, Chabner B, Schein P, Hubbard SP, Young RC. Advanced diffuse histiocytic lymphoma, a potentially curable disease. Lancet. 1975 Feb 1;1(7901):248-50. link to original article contains dosing details in manuscript PubMed
CNOP
CNOP: Cyclophosphamide, Novantrone (Mitoxantrone), Oncovin (Vincristine), Prednisone
MCOP: Mitoxantrone, Cyclophosphamide, Oncovin (Vincristine), Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sonneveld & Michiels 1990 | NR | Phase 2 | ||
Pavlovsky et al. 1992a | 1985-1988 | Phase 3 (E-switch-ic) | CHOP | Did not meet endpoint of OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Mitoxantrone (Novantrone) 10 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 50 mg/m2 PO once per day on days 1 to 5
28-day cycle for 6 cycles
References
- Sonneveld P, Michiels JJ. Full dose chemotherapy in elderly patients with non-Hodgkin's lymphoma: a feasibility study using a mitoxantrone containing regimen. Br J Cancer. 1990 Jul;62(1):105-8. link to original article link to PMC article contains dosing details in manuscript PubMed
- Pavlovsky S, Santarelli MT, Erazo A, Diaz Maqueo JC, Somoza N, Lluesma Goñalons M, Cervantes G, Garcia Vela EL, Corrado C, Magnasco H, Milone G. Results of a randomized study of previously-untreated intermediate and high grade lymphoma using CHOP versus CNOP. Ann Oncol. 1992 Mar;3(3):205-9. link to original article PubMed
- Update: Bezwoda W, Rastogi RB, Erazo Valla A, Diaz-Maqueo JC, Pavlovsky S, Morioka H, Resegotti L, Rueckle H, Somoza N, Moreno-Nogueira JA, Bernasconi C, Ho A, Burns I, Lardinois J, van der Merwe A, Richards E; Novantrone International Study Group. Long-term results of a multicentre randomised, comparative phase III trial of CHOP versus CNOP regimens in patients with intermediate- and high-grade non-Hodgkin's lymphomas. Eur J Cancer. 1995 Jun;31A(6):903-11. link to original article PubMed
CNOP (Prednisolone)
CNOP: Cyclophosphamide, Novantrone (Mitoxantrone), Oncovin (Vincristine), Prednisolone
MCOP: Mitoxantrone, Cyclophosphamide, Oncovin (Vincristine), Prednisolone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bessell et al. 2003 (CLG NH 3003) | 1993-2000 | Phase 3 (E-switch-ic) | Modified CHOP | Not designed to look at efficacy |
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Mitoxantrone (Novantrone) 10 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1 mg IV once on day 1
Glucocorticoid therapy
- Prednisolone (Millipred) 20 mg PO twice per day on days 1 to 5
21-day cycle for 6 cycles
References
- CLG NH 3003: Bessell EM, Burton A, Haynes AP, Glaholm J, Child JA, Cullen MH, Davies JM, Smith GM, Ellis IO, Jack A, Jones EL; Central Lymphoma Group UK. A randomised multicentre trial of modified CHOP versus MCOP in patients aged 65 years and over with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003 Feb;14(2):258-67. link to original article contains dosing details in manuscript PubMed NCT00002576
COMP
COMP: Cyclophosphamide, Oncovin (Vincristine), Methotrexate, Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Anderson et al. 1983 | 1977-1979 | Phase 3 (E-de-esc) | LSA2-L2 | Did not meet primary endpoint of FFS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV once per day on days 3, 10, 17, 24
- Methotrexate (MTX) 180 mg/m2 IV push, then 120 mg/m2 IV over 4 hours once on day 12
Glucocorticoid therapy
- Prednisone (Sterapred) 15 mg/m2 (maximum dose of 60 mg/day) PO four times per day on days 3 to 30, then taper off on days 31 to 37
CNS therapy, prophylaxis
- Methotrexate (MTX) 6.25 mg/m2 IT once per day on days 5, 31, 34
One course
Subsequent treatment
- COMP maintenance
References
- Anderson JR, Wilson JF, Jenkin DT, Meadows AT, Kersey J, Chilcote RR, Coccia P, Exelby P, Kushner J, Siegel S, Hammond D. Childhood non-Hodgkin's lymphoma: the results of a randomized therapeutic trial comparing a 4-drug regimen (COMP) with a 10-drug regimen (LSA2-L2). N Engl J Med. 1983 Mar 10;308(10):559-65. link to original article contains dosing details in manuscript PubMed
COP-Bleo
COP-Bleo: Cyclophosphamide, Oncovin (Vincristine), Prednisone, Bleomycin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Coltman et al. 1977 | 1966-1974 | Non-randomized | ||
Jones et al. 1979 | 1974-1977 | Phase 3 (C) | 1. CHOP-BCG 2. CHOP-B |
Might have inferior CR rate |
Note: to our knowledge, this regimen was not tested as an experimental arm in a RCT prior to becoming a standard comparator arm.
Chemotherapy
- Cyclophosphamide (Cytoxan) 125 mg/m2 PO once per day on days 1 to 14
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once per day on days 1 & 8
- Bleomycin (Blenoxane) 4 mg/m2 IV once per day on days 1 & 8
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
28-day cycles
References
- Coltman CA Jr, Luce JK, McKelvey EM, Jones SE, Moon TE; SWOG. Chemotherapy of non-Hodgkin's lymphoma: 10 years' experience in the Southwest Oncology Group. Cancer Treat Rep. 1977 Sep;61(6):1067-78. PubMed
- Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Butler JJ, Byrne GE Jr, Moon TE, Fisher R, Haskins CL, Coltman CA Jr; SWOG. Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study. Cancer. 1979 Feb;43(2):417-25. link to original article contains dosing details in manuscript PubMed
- Update: Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Talley R, Butler JJ, Byrne GE Jr, Hartsock R, Dixon D, Salmon SE. Improved complete remission rates and survival for patients with large cell lymphoma treated with chemoimmunotherapy: a Southwest Oncology Group Study. Cancer. 1983 Mar 15;51(6):1083-90. link to original article PubMed
CVP
CVP: Cyclophosphamide, Vincristine, Prednisone
COP: Cyclophosphamide, Oncovin (Vincristine), Prednisone
VCP: Vincristine, Cyclophosphamide, Prednisone
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hoogstraten et al. 1969 | NR | Phase 3 (E-esc) | 1. Cyclophosphamide | Superior CR rate |
2. CVP; lower-dose | Not reported |
Chemotherapy
- Cyclophosphamide (Cytoxan) 15 mg/kg IV once on day 1
- Vincristine (Oncovin) 25 mcg/kg IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 1 mg/kg PO once per day on days 1 to 7
7-day cycle for 6 cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Benjamin et al. 1976 | 1970-1973 | Randomized, fewer than 20 pts (E-de-esc) | MOPP | Not reported |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1500 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once per day on days 1 & 8
Glucocorticoid therapy
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 14
28-day cycles
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bagley et al. 1972 | 1967-1970 | Phase 2 | ||
Monfardini et al. 1977 | 1972-1974 | Phase 3 (C) | ABP | Did not meet endpoint of ORR |
Bajetta et al. 1988 | 1976-1984 | Phase 3 (C) | BACOP | Seems to have inferior FFFP |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
21-day cycles
References
- Hoogstraten B, Owens AH, Lenhard RE, Glidewell OJ, Leone LA, Olson KB, Harley JB, Townsend SR, Miller S, Spurr CL. Combination chemotherapy in lymphosarcoma and reticulum cell sarcoma. Blood. 1969 Feb;33(2):370-8. link to original article contains dosing details in manuscript PubMed
- Bagley CM Jr, Devita VT Jr, Berard CW, Canellos GP. Advanced lymphosarcoma: intensive cyclical combination chemotherapy with cyclophosphamide, vincristine, and prednisone. Ann Intern Med. 1972 Feb;76(2):227-34. link to original article PubMed
- Benjamin RS, Wiernik PH, O'Connell MJ, Chang P, Sutherland JC. A comparison of cyclophosphamide, vincristine, and prednisone (COP) with nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) in the treatment of nodular, poorly differentiated, lymphocytic lymphoma. Cancer. 1976 Nov;38(5):1896-902. link to original article contains dosing details in manuscript PubMed
- Monfardini S, Tancini G, De Lena M, Villa E, Valagussa P, Bonadonna G. Cyclophosphamide, vincristine, and prednisone (CVP) versus adriamycin, bleomycin, and prednisone (ABP) in stage IV non-Hodgkin's lymphomas. Med Pediatr Oncol. 1977;3(1):67-74. link to original article PubMed
- Bajetta E, Valagussa P, Bonadonna G, Lattuada A, Buzzoni R, Rilke F, Banfi A. Combined modality treatment for stage I-II non-Hodgkin's lymphomas: CVP versus BACOP chemotherapy. Int J Radiat Oncol Biol Phys. 1988 Jul;15(1):3-12. link to original article does not contain dosing details PubMed
Cyclophosphamide monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hoogstraten et al. 1969 | NR | Phase 3 (C) | CVP | Inferior CR rate |
References
- Hoogstraten B, Owens AH, Lenhard RE, Glidewell OJ, Leone LA, Olson KB, Harley JB, Townsend SR, Miller S, Spurr CL. Combination chemotherapy in lymphosarcoma and reticulum cell sarcoma. Blood. 1969 Feb;33(2):370-8. link to original article contains dosing details in manuscript PubMed
DA-EPOCH
DA-EPOCH: Dose Adjusted Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Wilson et al. 2002 | 1993-1999 | Phase 2 |
Chemotherapy
- Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m2)
- Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m2)
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 5
- Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 PO twice per day on days 1 to 5
Supportive therapy
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC greater than 5000/μL past nadir
- PCP prophylaxis with ONE of the following:
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day 3 days per week
- Atovaquone (Mepron) 1500 mg PO once per day
- Pentamidine (Nebupent) 300 mg nebulized every 28 days
21-day cycle for 6 to 8 cycles; begin new cycle every 21 days if ANC greater than 1000/μL and platelets greater than 100 x 109/L. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.
Dose and schedule modifications
- Start cycle 1 as described above.
- Obtain CBCs twice per week for nadir measurements.
- If nadir ANC greater than 500/μL, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
- If nadir ANC less than 500/μL on 1 or 2 measurements, use same doses as last cycle.
- If nadir ANC less than 500/μL on at least 3 measurements, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
- And/or if nadir platelet count less than 25 x 109/L on at least 1 measurement, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
- Dose adjustments below the cycle 1 starting dose only applies to cyclophosphamide. The lowest etoposide and doxorubicin would be dosed at is the original cycle 1 dose.
References
- Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, Steinberg SM, Little RF, Janik J, Gutierrez M, Raffeld M, Staudt L, Cheson BD, Longo DL, Harris N, Jaffe ES, Chabner BA, Wittes R, Balis F. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15;99(8):2685-93. link to original article contains dosing details in manuscript PubMed
DICEP
DICEP: Dose Intensive Cyclophosphamide, Etoposide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Stewart et al. 2006 | 1998-2004 | Phase 2 |
Preceding treatment
- CHOP induction x 1
Chemotherapy
- Cyclophosphamide (Cytoxan) 1750 mg/m2 IV over 2 hours once per day on days 1 to 3
- Etoposide (Vepesid) 350 mg/m2 IV over 2 hours once per day on days 1 to 3
- Cisplatin (Platinol) 35 mg/m2 IV over 2 hours once per day on days 1 to 3
Supportive therapy
- Mesna (Mesnex) 1750 mg/m2/day IV continuous infusion over 72 hours, started on day 1 (total dose: 5250 mg/m2)
- Filgrastim (Neupogen) by the following weight-based criteria:
- Less than 70 kg: 300 mcg SC once per day, started on day 14 and continued until stem cell collection completed
- 70 to 100 kg: 480 mcg SC once per day, started on day 14 and continued until stem cell collection completed
- More than 70 kg: 600 mcg SC once per day, started on day 14 and continued until stem cell collection completed
One course
Subsequent treatment
- BEAM, then auto HSCT consolidation
References
- Stewart DA, Bahlis N, Valentine K, Balogh A, Savoie L, Morris DG, Jones A, Brown C, Russell JA. Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2006 Jun 15;107(12):4623-7. Epub 2006 Feb 7. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
F-MACHOP
F-MACHOP: Fluorouracil, Methotrexate, Ara-C (Cytarabine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Amadori et al. 1985 | NR in abstract | Non-randomized |
Infanti et al. 1996 | 1991-1996 | Non-randomized |
Chemotherapy
- Fluorouracil (5-FU) 15 mg/kg IV over 6 hours once on day 2 (hours 36 to 42)
- Methotrexate (MTX) 500 mg/m2 IV over 6 hours once on day 6 (hours 60 to 66)
- Cytarabine (Ara-C) 1000 mg/m2 IV over 6 hours once on day 3 (hours 42 to 48)
- Cyclophosphamide (Cytoxan) 800 mg/m2 IV bolus once on day 2 (hour 36)
- Doxorubicin (Adriamycin) 60 mg/m2 IV bolus once on day 3 (hour 48)
- Vincristine (Oncovin) 0.5 mg/m2 IV bolus twice per day on day 1 (hours 0 and 12)
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 14
Supportive therapy
- Leucovorin (Folinic acid) 20 mg/m2 IV bolus at hours 84, 96, 108, 120
21-day cycle for 6 cycles
References
- Amadori S, Guglielmi C, Anselmo AP, Cimino G, Ruco LP, Papa G, Biagini C, Mandelli F. Treatment of diffuse aggressive non-Hodgkin's lymphomas with an intensive multi-drug regimen including high-dose cytosine arabinoside (F-MACHOP). Semin Oncol. 1985 Jun;12(2 Suppl 3):218-22. PubMed
- Update: Guglielmi C, Amadori S, Anselmo AP, Baroni CD, Biagini C, Cimino G, Papa G, Mandelli F. Sequential combination chemotherapy of high-grade non-Hodgkin's lymphoma with 5-fluorouracil, methotrexate, cytosine-arabinoside, cyclophosphamide, doxorubicin, vincristine, and prednisone (F-MACHOP). Cancer Invest. 1987;5(3):159-69. link to original article PubMed
- Update: Guglielmi C, Amadori S, Ruco LP, Mantovani L, Martelli M, Papa G, Mandelli F. Combination chemotherapy for the treatment of diffuse aggressive lymphomas: F-MACHOP update. Semin Oncol. 1987 Jun;14(2 Suppl 1):104-9. PubMed
- Update: Guglielmi C, Amadori S, Martelli M, Dragoni F, Mandelli F. The F-MACHOP sequential combination chemotherapy regimen in advanced diffuse aggressive lymphomas: long-term results. Ann Oncol. 1991 May;2(5):365-71. link to original article PubMed
- Infanti L, Silvestri F, Fanin R, Salmaso F, Zaja F, Barillari G, Patriarca F, Geromin A, Cerno M, Damiani D, Baccarani M. The F-MACHOP regimen in the treatment of aggressive non-Hodgkin's lymphomas: a single center experience in 72 patients. Haematologica. 1996 Nov-Dec;81(6):521-8. link to original article contains dosing details in manuscript PubMed
HOP
HOP: Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
APO: Adriamycin (Doxorubicin), Prednisone, Oncovin (Vincristine)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
McKelvey et al. 1976 | 1972-1974 | Phase 3 (E-de-esc) | CHOP | Did not meet endpoint of OS |
Laver et al. 2001 (POG 8615) | 1986-1991 | Phase 3 (C) | ACOP | Did not meet primary endpoint of EFS |
Laver et al. 2005 (POG 9315) | 1994-2000 | Non-randomized part of phase 3 RCT |
Chemotherapy
- Doxorubicin (Adriamycin) as follows:
- Cycles 1 to 6: 80 mg/m2 IV once on day 1
- Cycle 7: 70 mg/m2 IV once on day 1 (for a cumulative dose of 550 mg/m2)
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
14- to 21-day cycles
References
- McKelvey EM, Gottlieb JA, Wilson HE, Haut A, Talley RW, Stephens R, Lane M, Gamble JF, Jones SE, Grozea PN, Gutterman J, Coltman C, Moon TE. Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976 Oct;38(4):1484-93. link to original article contains dosing details in manuscript PubMed
- POG 8615: Laver JH, Mahmoud H, Pick TE, Hutchinson RE, Weinstein HJ, Schwenn M, Weitzman S, Murphy SB, Ochoa S, Shuster JJ; Pediatric Oncology Group. Results of a randomized phase III trial in children and adolescents with advanced stage diffuse large cell non Hodgkin's lymphoma: a Pediatric Oncology Group study. Leuk Lymphoma. 2001 Jul;42(3):399-405. link to original article PubMed
- POG 9315: Laver JH, Kraveka JM, Hutchison RE, Chang M, Kepner J, Schwenn M, Tarbell N, Desai S, Weitzman S, Weinstein HJ, Murphy SB. Advanced-stage large-cell lymphoma in children and adolescents: results of a randomized trial incorporating intermediate-dose methotrexate and high-dose cytarabine in the maintenance phase of the APO regimen: a Pediatric Oncology Group phase III trial. J Clin Oncol. 2005 Jan 20;23(3):541-7. link to original article PubMed NCT00002618
LD-ACOP-B
LD-ACOP-B: Low-Dose Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone, Bleomycin
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
O'Reilly et al. 1991 | 1983-1985 | Non-randomized |
Chemotherapy
- Cyclophosphamide (Cytoxan) 250 mg/m2 IV once per day on days 1, 15, 29
- Doxorubicin (Adriamycin) 25 mg/m2 IV once per day on days 1, 15, 29
- Vincristine (Oncovin) 1.2 mg/m2 (maximum dose of 2 mg) IV once per day on days 8, 22, 36
- Bleomycin (Blenoxane) 10 units/m2 IV once per day on days 8, 22, 36
Glucocorticoid therapy
- Prednisone (Sterapred) as follows:
- Cycle 1: 50 mg PO once per day on days 1 to 42
- Cycle 2: 50 mg PO once every other day on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41
Supportive therapy
42-day cycle for 2 cycles
References
- O'Reilly SE, Klimo P, Connors JM. Low-dose ACOP-B and VABE: weekly chemotherapy for elderly patients with advanced-stage diffuse large-cell lymphoma. J Clin Oncol. 1991 May;9(5):741-7. link to original article contains dosing details in manuscript PubMed
MACOP-B
MACOP-B: Methotrexate, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone, Bleomycin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Klimo et al. 1985a | 1981-1984 | Non-randomized | ||
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) | 1986-1991 | Phase 3 (E-esc) | 1. CHOP 2. m-BACOD 3. ProMACE-CytaBOM |
Did not meet endpoint of OS |
Sertoli et al. 1994 | 1987-1991 | Phase 3 (E-switch-ic) | ProMACE-MOPP | Did not meet endpoint of OS36 |
Gianni et al. 1997 | 1987-NR | Phase 3 (C) | High-dose sequential therapy | Inferior EFS |
Chemotherapy
- Methotrexate (MTX) 400 mg/m2 IV once per week on weeks 2, 6, 10
- Doxorubicin (Adriamycin) 50 mg/m2 IV once per week on weeks 1, 3, 5, 7, 9, 11
- Cyclophosphamide (Cytoxan) 350 mg/m2 IV once per week on weeks 1, 3, 5, 7, 9, 11
- Vincristine (Oncovin) 1.4 mg/m2 IV once per week on weeks 2, 4, 6, 8, 10, 12
- Bleomycin (Blenoxane) 10 units/m2 IV once per week on weeks 4, 8, 12
Glucocorticoid therapy
- Prednisone (Sterapred) 75 mg PO once per day, tapered over last 15 days (schedule not reported)
CNS therapy, prophylaxis
- (for patients with bone marrow involvement):
- Methotrexate (MTX) 12 mg IV
Supportive therapy
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 2 tablets (not specified if SS or DS) PO twice per day
12-week course
References
- Klimo P, Connors JM. MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med. 1985 May;102(5):596-602. link to original article PubMed
- Update: Klimo P, Connors JM. Updated clinical experience with MACOP-B. Semin Hematol. 1987 Apr;24(2 Suppl 1):26-34. PubMed
- SWOG-8516: Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. link to original article PubMed
- Update: Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group. J Clin Oncol. 2009 Jan 1;27(1):114-9. Epub 2008 Dec 1. link to original article link to PMC article PubMed
- Sertoli MR, Santini G, Chisesi T, Congiu AM, Rubagotti A, Contu A, Salvagno L, Coser P, Porcellini A, Vespignani M, Capnist G, Rossi E, Mangoni L, Fabris P, Vinante O, Tedeschi L, Endrizzi L, Miglio LP, Perrotta A, Rosso R, Damasio E, Rizzoli V. MACOP-B versus ProMACE-MOPP in the treatment of advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group. J Clin Oncol. 1994 Jul;12(7):1366-74. link to original article PubMed
- Gianni AM, Bregni M, Siena S, Brambilla C, Di Nicola M, Lombardi F, Gandola L, Tarella C, Pileri A, Ravagnani F, Valagussa P, Bonadonna G. High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. N Engl J Med. 1997 May 1;336(18):1290-7. link to original article PubMed
- Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains dosing details in manuscript PubMed
- Update: Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. Epub 2011 Sep 21. link to original article contains dosing details in abstract PubMed
m-BACOD
m-BACOD: methotrexate (moderate dose), Bleomycin, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Dexamethasone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Skarin et al. 1983 | 1976-1981 | Non-randomized | ||
Shipp et al. 1990 | 1981-1986 | Non-randomized | ||
Gherlinzoni et al. 1990 | 1984-1986 | Phase 3 (C) | m-BNCOD | Did not meet endpoints of OS/RFS |
Gordon et al. 1992 | 1984-1988 | Phase 3 (E-esc) | CHOP | Did not meet endpoint of OS |
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) | 1986-1991 | Phase 3 (E-esc) | 1. CHOP 2. MACOP-B 3. ProMACE-CytaBOM |
Did not meet endpoint of OS |
Tilly et al. 2000 (LNH87-1) | 1987-1993 | Phase 3 (C) | ACVBP | Did not meet primary endpoint of FFS |
Chemotherapy
- Methotrexate (MTX) 200 mg/m2 IV once per day on days 8 & 15
- Bleomycin (Blenoxane) 4 units/m2 IV once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1 mg/m2 (maximum dose of 2 mg) IV once on day 1
Glucocorticoid therapy
- Dexamethasone (Decadron) 6 mg/m2 (no route specified) once per day on days 1 to 5
Supportive therapy
- Leucovorin (Folinic acid) 10 mg/m2 IV or PO every 6 hours on days 9 & 10, 16 & 17, starting 24 hours after each methotrexate
21-day cycle for 10 cycles
Dose and schedule modifications
- If nadir WBC <1,000 or nadir platelets less than 50,000: 50% of cyclophosphamide and doxorubicin
- If WBC <1,000, platelets less than 50,000, or creatinine >50% of baseline on day of treatment, methotrexate was omitted
References
- Skarin AT, Canellos GP, Rosenthal DS, Case DC Jr, MacIntyre JM, Pinkus GS, Moloney WC, Frei E 3rd. Improved prognosis of diffuse histiocytic and undifferentiated lymphoma by use of high dose methotrexate alternating with standard agents (M-BACOD). J Clin Oncol. 1983 Feb;1(2):91-8. link to original article PubMed
- Gherlinzoni F, Guglielmi C, Mazza P, Amadori S, Mandelli F, Tura S. Phase III comparative trial (m-BACOD v m-BNCOD) in the treatment of stage II to IV non-Hodgkin's lymphomas with intermediate- or high-grade histology. Semin Oncol. 1990 Dec;17(6 Suppl 10):3-8. PubMed
- Shipp MA, Yeap BY, Harrington DP, Klatt MM, Pinkus GS, Jochelson MS, Rosenthal DS, Skarin AT, Canellos GP. The m-BACOD combination chemotherapy regimen in large-cell lymphoma: analysis of the completed trial and comparison with the M-BACOD regimen. J Clin Oncol. 1990 Jan;8(1):84-93. link to original article contains dosing details in manuscript PubMed
- Gordon LI, Harrington D, Andersen J, Colgan J, Glick J, Neiman R, Mann R, Resnick GD, Barcos M, Gottlieb A, O'Connell M. Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma. N Engl J Med. 1992 Nov 5;327(19):1342-9. link to original article PubMed
- SWOG 8516: Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. link to original article PubMed
- Update: Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group. J Clin Oncol. 2009 Jan 1;27(1):114-9. Epub 2008 Dec 1. link to original article link to PMC article PubMed
- LNH87-1: Tilly H, Mounier N, Lederlin P, Brière J, Dupriez B, Sebban C, Bosly A, Biron P, Nouvel C, Herbrecht R, Bordessoule D, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte. Randomized comparison of ACVBP and m-BACOD in the treatment of patients with low-risk aggressive lymphoma: the LNH87-1 study. J Clin Oncol. 2000 Mar;18(6):1309-15. link to original article PubMed
m-BNCOD
m-BNCOD: methotrexate (moderate dose), Bleomycin, Novantrone (Mitoxantrone), Cyclophosphamide, Oncovin (Vincristine), Dexamethasone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gherlinzoni et al. 1990 | 1984-1986 | Phase 3 (E-switch-ic) | m-BACOD | Did not meet endpoints of OS/RFS |
Note: The abstract does not contain treatment details, and the original manuscript is not available online.
Chemotherapy
- Methotrexate (MTX)
- Bleomycin (Blenoxane)
- Mitoxantrone (Novantrone)
- Cyclophosphamide (Cytoxan)
- Vincristine (Oncovin)
Glucocorticoid therapy
References
- Gherlinzoni F, Guglielmi C, Mazza P, Amadori S, Mandelli F, Tura S. Phase III comparative trial (m-BACOD v m-BNCOD) in the treatment of stage II to IV non-Hodgkin's lymphomas with intermediate- or high-grade histology. Semin Oncol. 1990 Dec;17(6 Suppl 10):3-8. PubMed
P/DOCE
P/DOCE: Prednisone, Doxorubicin, Oncovin (Vincristine), Cyclophosphamide, Etoposide,
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
O'Reilly et al. 1993 | 1988-1991 | Phase 2 |
Note: although the drugs are the same as those used in CHOEP, the doses are significantly different and this was intended for elderly persons (65+ years of age). Although the original paper described this as an 8-week protocol, we express it here in cyclic fashion.
Glucocorticoid therapy
- Prednisone (Sterapred) 50 mg/day PO on days 1 to 10
Chemotherapy
- Doxorubicin (Adriamycin) as follows:
- Cycles 1 & 3: 40 mg/m2 IV once per day on days 1 & 8
- Vincristine (Oncovin) 1.2 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 300 mg/m2 IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycle 2: 50 mg/m2 IV once on day 1, then 100 mg/m2 PO once per day on days 2 to 5
21-day cycle for 3 cycles
References
- O'Reilly SE, Connors JM, Howdle S, Hoskins P, Klasa R, Klimo P, Stuart DS. In search of an optimal regimen for elderly patients with advanced-stage diffuse large-cell lymphoma: results of a phase II study of P/DOCE chemotherapy. J Clin Oncol. 1993 Nov;11(11):2250-7. link to original article contains dosing details in manuscript PubMed
PACEBOM
PACEBOM: Prednisolone, Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide, Bleomycin, Oncovin (Vincristine), Methotrexate
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Linch et al. 2000 | 1987-1991 | Phase 3 (E-esc) | CHOP | Might have superior cause-specific survival |
Note: the text suggests that this is an 11-week protocol, but table 1 indicates it to be 12 weeks.
Glucocorticoid therapy
- Prednisolone (Millipred) as follows:
- Cycles 1 to 4: 50 mg PO once per day
- Cycles 5 to 12: 50 mg PO once every other day
Chemotherapy
- Doxorubicin (Adriamycin) as follows:
- Cycles 1, 3, 5, 7, 9, 11: 35 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 1, 3, 5, 7, 9, 11: 300 mg/m2 IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1, 3, 5, 7, 9, 11: 150 mg/m2 IV once on day 1
- Bleomycin (Blenoxane) as follows:
- Cycles 2, 4, 6, 8, 10, 12: 10 mg/m2 IV once on day 1
- Vincristine (Oncovin) as follows:
- Cycles 2, 4, 6, 8, 10, 12: 1.4 mg/m2 IV once on day 1
- Methotrexate (MTX) as follows:
- Cycles 2, 4, 6, 8, 10, 12: 100 mg/m2 IV once on day 1
7-day cycle for 12 cycles (see note)
References
- Linch DC, Smith P, Hancock BW, Hoskin PJ, Cunningham DC, Newland AC, Milligan D, Stevenson PA, Wood JK, Maclennan KA, Vaughan B, Vaughan G, Gregory WM; British National Lymphoma Investigation. A randomized British National Lymphoma Investigation trial of CHOP vs a weekly multi-agent regimen (PACEBOM) in patients with histologically aggressive non-Hodgkin's lymphoma. Ann Oncol. 2000;11 Suppl 1:87-90. link to original article contains dosing details in manuscript PubMed
PEN
PEN: Prednisone, Etoposide, Novantrone (Mitoxantrone)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Goss et al. 1995 | 1991-1993 | Phase 2 |
Glucocorticoid therapy
- Prednisone (Sterapred) 50 mg PO once per day on days 1 to 14
Chemotherapy
- Etoposide (Vepesid) 50 mg PO once per day on days 1 to 14
- Mitoxantrone (Novantrone) 8 mg/m2 IV once on day 1
28-day cycles
References
- Goss P, Burkes R, Rudinskas L, King M, Chow W, Myers R, Davidson M, Poldre P, Crump M, Sutton D, Scott G. A phase II trial of prednisone, oral etoposide, and novantrone (PEN) as initial treatment of non-Hodgkin's lymphoma in elderly patients. Leuk Lymphoma. 1995 Jun;18(1-2):145-52. link to original article contains dosing details in abstract PubMed
PMitCEBO
PMitCEBO: Prednisolone, Mitoxantrone, Cyclophosphamide, Etoposide, Bleomycin, Oncovin (Vincristine)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mainwaring et al. 2001 | 1993-1997 | Phase 3 (E-switch-ic) | PAdriaCEBO | Superior OS |
Burton et al. 2006 (BNLI CHOPVPMITCEBO-GOODRISK) | 1997-1999 | Phase 3 (E-esc) | CHOP | Did not meet primary endpoint of FFS |
Pfreundschuh et al. 2006 (NCIC-CTG LY.9) | 2000-2003 | Phase 3 (C) | 1a. R-CHOP 1b. R-CHOEP 1c. R-MACOP-B 1d. R-PMitCEBO |
Inferior EFS1 |
1Reported efficacy is based on the 2011 update.
Glucocorticoid therapy
- Prednisolone (Millipred) as follows:
- Cycles 1 to 4: 50 mg PO once per day on days 1 to 7
- Cycles 5 up to 16: 50 mg PO once every other day
Chemotherapy
- Mitoxantrone (Novantrone) 7 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 300 mg/m2 IV once on day 1
- Etoposide (Vepesid) 150 mg/m2 IV once on day 1
- Bleomycin (Blenoxane) 10 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
7-day cycle for up to 16 cycles
References
- Mainwaring PN, Cunningham D, Gregory W, Hoskin P, Hancock B, Norton AJ, MacLennan K, Smith P, Vaughan Hudson G, Linch D. Mitoxantrone is superior to doxorubicin in a multiagent weekly regimen for patients older than 60 with high-grade lymphoma: results of a BNLI randomized trial of PAdriaCEBO versus PMitCEBO. Blood. 2001 May 15;97(10):2991-7. link to original article PubMed
- BNLI CHOPVPMITCEBO-GOODRISK: Burton C, Linch D, Hoskin P, Milligan D, Dyer MJ, Hancock B, Mouncey P, Smith P, Qian W, MacLennan K, Jack A, Webb A, Cunningham D. A phase III trial comparing CHOP to PMitCEBO with or without G-CSF in patients aged 60 plus with aggressive non-Hodgkin's lymphoma. Br J Cancer. 2006 Mar 27;94(6):806-13. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00005867
- NCIC-CTG LY.9: Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains dosing details in manuscript PubMed NCT00064116
- Update: Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. Epub 2011 Sep 21. link to original article contains dosing details in abstract PubMed
ProMACE-CytaBOM
ProMACE-CytaBOM: Prolix (Prednisone), Methotrexate, Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide, Cytarabine, Bleomycin, Oncovin (Vincristine), Methotrexate
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Longo et al. 1991 | 1981-1988 | Phase 3 (E-switch-ic) | ProMACE-MOPP | Seems to have superior OS |
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) | 1986-1991 | Phase 3 (E-esc) | 1. CHOP 2. MACOP-B 3. m-BACOD |
Did not meet endpoint of OS |
Glucocorticoid therapy
- Prednisone (Prolix) 60 mg/m2 PO once per day on days 1 to 14
Chemotherapy
- Methotrexate (MTX) 120 mg/m2 IV once on day 8
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once on day 1
- Cytarabine (Ara-C) 300 mg/m2 IV once on day 8
- Bleomycin (Blenoxane) 5 units/m2 IV once on day 8
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 8
Supportive therapy
- Leucovorin (Folinic acid) 25 mg/m2 PO every 6 hours on day 9, starting 24 hours after methotrexate
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day throughout the course of treatment
21-day cycle for 6 cycles or 2 cycles after maximum clinical response
CNS therapy, prophylaxis
- Patients with initial bone or bone marrow involvement who achieved a CR were treated with 2400 cGy prophylactic cranial irradiation.
Dose and schedule modifications
- "If WBC count is at least 4 x 109/L, use 100% doses of all drugs
- If WBC count is 3 to 3.999 x 109/L, 100% prednisone, bleomycin, vincristine, cytarabine, and methotrexate; 75% cyclophosphamide, doxorubicin, and etoposide
- If WBC count is 2 to 2.999 x 109/L, 100% prednisone, bleomycin, vincristine, and methotrexate; 75% etoposide, cytarabine; 50% cyclophosphamide, doxorubicin
- If WBC count is 1 to 1.999 x 109/L, 100% prednisone, bleomycin, vincristine and methotrexate; 25% cyclophosphamide, doxorubicin, etoposide, and cytarabine
- If WBC count is 0 to 0.999 x 109/L, 100% prednisone, vincristine, and bleomycin; 50% methotrexate, no other drugs
- If platelet count is at least 100 x 109/L, use 100% doses of all drugs
- If platelet count is 50 to 99 x 109/L, 100% prednisone, bleomycin, vincristine, and methotrexate; 50% etoposide and cytarabine; 25% cyclophosphamide and doxorubicin
- If platelet count is 0 to 49 x 109/L, 100% prednisone, bleomycin, and vincristine; 50% methotrexate, no other drugs"
References
- Longo DL, DeVita VT Jr, Duffey PL, Wesley MN, Ihde DC, Hubbard SM, Gilliom M, Jaffe ES, Cossman J, Fisher RI, Young RC. Superiority of ProMACE-CytaBOM over ProMACE-MOPP in the treatment of advanced diffuse aggressive lymphoma: results of a prospective randomized trial. J Clin Oncol. 1991 Jan;9(1):25-38. Erratum in: J Clin Oncol 1991 Apr;9(4):710. link to original article contains dosing details in manuscript PubMed
- SWOG-8516: Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. link to original article PubMed
- Update: Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group. J Clin Oncol. 2009 Jan 1;27(1):114-9. Epub 2008 Dec 1. link to original article link to PMC article PubMed
ProMACE-MOPP
ProMACE-MOPP: Prolix (Prednisone), Methotrexate, Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide, Mustargen (Mechlorethamine), Oncovin (Vincristine), Procarbazine, Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fisher et al. 1983 | 1977-1981 | Non-randomized | ||
Longo et al. 1991 | 1981-1988 | Phase 3 (C) | ProMACE-CytaBOM | Seems to have inferior OS |
Somers et al. 1994 (EORTC 20855) | 1986-1991 | Phase 3 (E-switch-ic) | CHVmP-VB | Superior ORR |
Sertoli et al. 1994 | 1987-1991 | Phase 3 (C) | MACOP-B | Did not meet endpoint of OS36 |
Chemotherapy
- Methotrexate (MTX) 500 mg/m2 IV once on day 15
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once on day 1
- Mechlorethamine (Mustargen) 6 mg/m2 IV once on day 8
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 8
- Procarbazine (Matulane) 100 mg/m2 PO once per day on days 8 to 15
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 15
28-day cycle for 8 cycles
References
- Fisher RI, DeVita VT Jr, Hubbard SM, Longo DL, Wesley R, Chabner BA, Young RC. Diffuse aggressive lymphomas: increased survival after alternating flexible sequences of proMACE and MOPP chemotherapy. Ann Intern Med. 1983 Mar;98(3):304-9. link to original article PubMed
- Longo DL, DeVita VT Jr, Duffey PL, Wesley MN, Ihde DC, Hubbard SM, Gilliom M, Jaffe ES, Cossman J, Fisher RI, Young RC. Superiority of ProMACE-CytaBOM over ProMACE-MOPP in the treatment of advanced diffuse aggressive lymphoma: results of a prospective randomized trial. J Clin Oncol. 1991 Jan;9(1):25-38. Erratum in: J Clin Oncol 1991 Apr;9(4):710. link to original article PubMed
- EORTC 20855: Somers R, Carde P, Thomas J, Tirelli U, Keuning JJ, Bron D, Delmer A, de Bock R, De Wolf-Peeters C, van Glabbeke M, Duez N. EORTC study of non-Hodgkin's lymphoma: phase III study comparing CHVmP-VB and ProMACE-MOPP in patients with stage II, III, and IV intermediate- and high-grade lymphoma. Ann Oncol. 1994;5 Suppl 2:85-9. Erratum in: Ann Oncol 1994 May;5(5):475. link to original article contains dosing details in manuscript PubMed
- Sertoli MR, Santini G, Chisesi T, Congiu AM, Rubagotti A, Contu A, Salvagno L, Coser P, Porcellini A, Vespignani M, Capnist G, Rossi E, Mangoni L, Fabris P, Vinante O, Tedeschi L, Endrizzi L, Miglio LP, Perrotta A, Rosso R, Damasio E, Rizzoli V. MACOP-B versus ProMACE-MOPP in the treatment of advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group. J Clin Oncol. 1994 Jul;12(7):1366-74. link to original article does not contain dosing details PubMed
R-CHMP
R-CHMP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Marqibo (Vincristine liposomal), Prednisone
Regimen variant #1, 3 cycles
Study | Dates of enrollment | Evidence |
---|---|---|
Hagemeister et al. 2013 | 2001-2002 | Phase 2 |
Note: This regimen was intended for stage I patients with no LN greater than 5 cm.
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine liposomal (Marqibo) 2 mg/m2 IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 3 cycles
Subsequent treatment
- RT consolidation
Regimen variant #2, 6 cycles
Study | Dates of enrollment | Evidence |
---|---|---|
Hagemeister et al. 2013 | 2001-2002 | Phase 2 |
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine liposomal (Marqibo) 2 mg/m2 IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 6 cycles
References
- Hagemeister F, Rodriguez MA, Deitcher SR, Younes A, Fayad L, Goy A, Dang NH, Forman A, McLaughlin P, Medeiros LJ, Pro B, Romaguera J, Samaniego F, Silverman JA, Sarris A, Cabanillas F. Long term results of a phase 2 study of vincristine sulfate liposome injection (Marqibo(®) ) substituted for non-liposomal vincristine in cyclophosphamide, doxorubicin, vincristine, prednisone with or without rituximab for patients with untreated aggressive non-Hodgkin lymphomas. Br J Haematol. 2013 Sep;162(5):631-8. Epub 2013 Jun 27. link to original article contains dosing details in manuscript PubMed
VABE
VABE: Vincristine, Adriamycin (Doxorubicin), Bleomycin, Etoposide, Prednisone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
O'Reilly et al. 1991 | 1983-1985 | Non-randomized |
Chemotherapy
- Vincristine (Oncovin) 1 mg/m2 (maximum dose of 2 mg) IV once on day 8
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Bleomycin (Blenoxane) 5 units/m2 IV once on day 8
- Etoposide (Vepesid) 80 mg/m2 IV once on day 1, then 160 mg/m2 PO once on day 2
Glucocorticoid therapy
- Prednisone (Sterapred) as follows:
- Cycles 1 to 3: 50 mg PO once per day on days 1 to 14
- Cycles 4 to 6: 50 mg PO once every other day on days 1, 3, 5, 7, 9, 11, 13
Supportive therapy
- Hydrocortisone (Cortef) 100 mg IV once on day 8, given with bleomycin
- Cotrimoxazole
- Cimetidine (Tagamet)
- Ketoconazole (Nizoral)
14-day cycle for 6 cycles
References
- O'Reilly SE, Klimo P, Connors JM. Low-dose ACOP-B and VABE: weekly chemotherapy for elderly patients with advanced-stage diffuse large-cell lymphoma. J Clin Oncol. 1991 May;9(5):741-7. link to original article contains dosing details in manuscript PubMed
VACOP-B
VACOP-B: Vepesid (Etoposide), Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone, Bleomycin
P-VABEC: Prednisone, Vincristine, Adriamycin (Doxorubicin), Bleomycin, Etoposide, Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Pichert et al. 1992 | Retrospective | |
Martelli et al. 1993 | 1988-1990 | Phase 2 |
Chemotherapy
- Etoposide (Vepesid) 100 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 30 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 350 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.2 mg/m2 (maximum dose of 2 mg) IV once on day 8
- Bleomycin (Blenoxane) 5 mg/m2 IV once on day 8
Glucocorticoid therapy
- Prednisone (Sterapred) 50 mg PO once per day on days 1 to 14
14-day cycle for 6 cycles
References
- Retrospective: Pichert G, Peters J, Stahel RA, Dommann C, Joss R, Gebbers JO, Kroner T, Sulser H, Honegger HP, Maurer R, Pampallona S. Chemotherapy with MACOP-B and VACOP-B for intermediate- and high-grade non-Hodgkin's lymphoma: clinical results and analysis of prognostic factors. Ann Oncol. 1992 Sep;3(8):645-9. link to original article PubMed
- Martelli M, Guglielmi C, Coluzzi S, Avvisati G, Amadori S, Giovannini M, Torromeo C, Mandelli F. P-VABEC: a prospective study of a new weekly chemotherapy regimen for elderly aggressive non-Hodgkin's lymphoma. J Clin Oncol. 1993 Dec;11(12):2362-9. link to original article contains dosing details in manuscript PubMed
VCAP
VCAP: Vindesine, Cyclophosphamide, Adriamycin (Doxorubicin), Prednisone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Bernard et al. 2005 | 1984-1996 | Phase 2 |
Chemotherapy
- Vindesine (Eldisine) 4 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 1500 mg/m2 IV once on day 2
- Doxorubicin (Adriamycin) 80 mg/m2 IV once on day 2
Glucocorticoid therapy
- Prednisone (Sterapred) 80 mg/m2 PO once per day on days 1 to 5
CNS therapy, prophylaxis
- Methotrexate (MTX) 15 mg IT once on day not specified (3 doses total)
21-day cycle for 3 cycles
References
- Bernard M, Cartron G, Rachieru P, LeMevel A, Branger B, Le Maignan C, Berthou C, Ghandour C, Delwail V, Milpied N, Cassasus P, Celigny PS, Guyotat D, Lamy T, Desablens B; GOELAMS. Long-term outcome of localized high-grade non-Hodgkin's lymphoma treated with high dose CHOP regimen and involved field radiotherapy: results of a GOELAMS study. Haematologica. 2005 Jun;90(6):802-9. link to original article contains dosing details in manuscript PubMed
VEPA
VEPA: Vincristine, Endoxan (Cyclophosphamide), Prednisolone, Adriamycin (Doxorubicin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shimoyama et al. 1988 (JCOG8101) | 1981-1983 | Phase 3 (C) | VEPA-M | Did not meet efficacy endpoints |
Note: while the drugs are the same as those used in CHOP, administration details vary significantly; see paper for details.
Chemotherapy
- Vincristine (Oncovin) 1 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
- Cyclophosphamide (Cytoxan) 350 mg/m2 IV once per day on days 1, 8, 15
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
Glucocorticoid therapy
- Prednisolone (Millipred) 40 mg/m2 PO once per day on days 1 to 3, 8 to 10, 15 to 17
21-day cycle for 2 cycles
References
- JCOG8101: Shimoyama M, Ota K, Kikuchi M, Yunoki K, Konda S, Takatsuki K, Ichimaru M, Ogawa M, Kimura I, Tominaga S, Tsugane S, Taguchi H, Minato K, Takenaka T, Tobinai K, Kurita S, Oyama A, Hisano S, Kozuru M, Matsumoto M, Nomura K, Takiguchi T, Sugai S, Yamaguchi K, Hattori T, Kinoshita K, Tajima K, Suemasu K. Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M. J Clin Oncol. 1988 Jan;6(1):128-41. link to original article contains dosing details in manuscript PubMed
VNCOP-B
VNCOP-B: Vepesid (Etoposide), Novantrone (Mitoxantrone), Cyclophosphamide, Oncovin (Vincristine), Prednisone, Bleomycin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zinzani et al. 1997 | 1993-1995 | Phase 3 (C) | VNCOP-B & G-CSF | Did not meet endpoint of RFS |
Zinzani et al. 2002 | 1996-2001 | Phase 3 (C) | VNCOP-B & G-CSF x 12 wk | Did not meet endpoint of RFS60 |
Chemotherapy
- Etoposide (Vepesid) 150 mg/m2 IV once on day 8
- Mitoxantrone (Novantrone) 10 mg/m2 IV once per day on days 1 & 15
- Cyclophosphamide (Cytoxan) 300 mg/m2 IV once per day on days 1 & 15
- Vincristine (Oncovin) 2 mg IV once per day on days 8 & 22
- Bleomycin (Blenoxane) 10 mg/m2 IV once on day 22
Glucocorticoid therapy
- Prednisone (Sterapred) as follows:
- Cycle 1: 40 mg IM once per day on days 1 to 28
- Cycle 2: 40 mg IM once per day on days 1 to 14, then tapered over the next 2 weeks
28-day cycle for 2 cycles
References
- Zinzani PL, Pavone E, Storti S, Moretti L, Fattori PP, Guardigni L, Falini B, Gobbi M, Gentilini P, Lauta VM, Bendandi M, Gherlinzoni F, Magagnoli M, Venturi S, Aitini E, Tabanelli M, Leone G, Liso V, Tura S. Randomized trial with or without granulocyte colony-stimulating factor as adjunct to induction VNCOP-B treatment of elderly high-grade non-Hodgkin's lymphoma. Blood. 1997 Jun 1;89(11):3974-9. link to original article contains dosing details in manuscript PubMed
- Zinzani PL, Gherlinzoni F, Storti S, Zaccaria A, Pavone E, Moretti L, Gentilini P, Guardigni L, De Renzo A, Fattori PP, Falini B, Lauta VM, Mannina D, Zaja F, Mazza P, Volpe E, Lauria F, Aitini E, Ciccone F, Tani M, Stefoni V, Alinari L, Baccarani M, Tura S. Randomized trial of 8-week versus 12-week VNCOP-B plus G-CSF regimens as front-line treatment in elderly aggressive non-Hodgkin's lymphoma patients. Ann Oncol. 2002 Sep;13(9):1364-9. link to original article PubMed
VR-CHOP
VR-CHOP: Velcade (Bortezomib), Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne
RB-CHOP: Rituximab, Bortezomib, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ruan et al. 2010 (Cornell 0309006313) | 2004-2007 | Phase 2 | ||
Leonard et al. 2017 (C05013) | 2009-2013 | Randomized Phase 2 (E-esc) | R-CHOP | Did not meet primary endpoint of PFS |
Targeted therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1 & 4
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive therapy
- Cornell 0309006313: "Standard" Acetaminophen (Tylenol) and Diphenhydramine (Benadryl) prior to rituximab
- C05013: Prophylaxis against VZV and PJP were recommended
21-day cycle for 6 cycles
References
- Cornell 0309006313: Ruan J, Martin P, Furman RR, Lee SM, Cheung K, Vose JM, Lacasce A, Morrison J, Elstrom R, Ely S, Chadburn A, Cesarman E, Coleman M, Leonard JP. Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Feb 20;29(6):690-7. Epub 2010 Dec 28. link to original article contains dosing details in manuscript PubMed NCT00151320
- C05013: Leonard JP, Kolibaba KS, Reeves JA, Tulpule A, Flinn IW, Kolevska T, Robles R, Flowers CR, Collins R, DiBella NJ, Papish SW, Venugopal P, Horodner A, Tabatabai A, Hajdenberg J, Park J, Neuwirth R, Mulligan G, Suryanarayan K, Esseltine DL, de Vos S. Randomized phase II study of R-CHOP with or without bortezomib in previously untreated patients with non-germinal center B-cell-like diffuse large B-cell lymphoma. J Clin Oncol. 2017 Nov 1;35(31):3538-3546. Epub 2017 Sep 1. link to original article contains dosing details in manuscript PubMed NCT00931918
- REMoDL-B: Davies A, Cummin TE, Barrans S, Maishman T, Mamot C, Novak U, Caddy J, Stanton L, Kazmi-Stokes S, McMillan A, Fields P, Pocock C, Collins GP, Stephens R, Cucco F, Clipson A, Sha C, Tooze R, Care MA, Griffiths G, Du MQ, Westhead DR, Burton C, Johnson PWM. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. Lancet Oncol. 2019 May;20(5):649-662. Epub 2019 Apr 1. link to original article link to PMC article PubMed NCT01324596
Consolidation after upfront therapy
Cyclophosphamide & TBI, then auto HSCT
Cy/TBI: Cyclophosphamide & Total Body Irradiation
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Takvorian et al. 1987 | 1982-1987 | Non-randomized |
Chemotherapy
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
Radiotherapy
- Total body irradiation (TBI) 1200 cGy in fractions on days –6 to –4 (pulmonary dosage was limited to 800 cGy)
References
- Takvorian T, Canellos GP, Ritz J, Freedman AS, Anderson KC, Mauch P, Tarbell N, Coral F, Daley H, Yeap B, Schlossman SF, Nadler LM. Prolonged disease-free survival after autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma with a poor prognosis. N Engl J Med. 1987 Jun 11;316(24):1499-505. link to original article PubMed
Cytarabine & Methotrexate (CYM)
CYM: CYtarabine, Methotrexate
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Milpied et al. 2004 (GOELAMS 072) | 1994-1999 | Non-randomized part of phase 3 RCT |
Preceding treatment
- Induction CEEP x 2
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 120 hours, started on day 37 (total dose: 500 mg/m2)
- Methotrexate (MTX) 3000 mg/m2 IV once on day 1
65-day course
Subsequent treatment
- BEAM with auto HSCT intensification
References
- GOELAMS 072: Milpied N, Deconinck E, Gaillard F, Delwail V, Foussard C, Berthou C, Gressin R, Lucas V, Colombat P, Harousseau JL; Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang. Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. N Engl J Med. 2004 Mar 25;350(13):1287-95. link to original article contains dosing details in manuscript PubMed
Relapsed or refractory, salvage therapy
DHAP
DHAP: Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Velasquez et al. 1988 | 1984-1986 | Phase 2 | ||
Philip et al. 1995 (PARMA) | 1987-1994 | Phase 3 (C) | DHAP x 2, then BEAC | Seems to have inferior OS |
Josting et al. 2005 | NR | Phase 2 |
Note: Velasquez et al. 1988 reported giving 6 to 10 courses, usually 4 courses beyond maximum response. To our knowledge, this regimen was not tested as an experimental arm in a RCT prior to becoming a standard comparator arm.
Glucocorticoid therapy
- Dexamethasone (Decadron) 40 mg IV over 15 minutes once per day on days 1 to 4
Chemotherapy
- Cytarabine (Ara-C) by the following age-based criteria:
- Younger than 70 years old: 2000 mg/m2 IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m2)
- Older than 70 years old: 1000 mg/m2 IV over 3 hours every 12 hours on day 2 (total dose per cycle: 2000 mg/m2)
- Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours, started on day 1
Supportive therapy
- Metoclopramide (Reglan) 1 mg/kg (route and frequency not indicated)
- Diphenhydramine (Benadryl) 25 mg IV (frequency not indicated)
21- to 28-day cycle for 2 cycles (PARMA & Josting et al. 2005) or up to 10 cycles (see note)
Subsequent treatment
- PARMA, responders (PR/CR) after cycle 2: DHAP x 4 versus BEAC, then autologous HSCT consolidation
- Josting et al. 2005, responders (PR/CR) after cycle 2: HD-MTX with stem cell mobilization, then HDT, then autologous HSCT consolidation
References
- Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, Barlogie B. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117-22. link to original article contains dosing details in manuscript PubMed
- PARMA: Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin F. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. link to original article does not contain dosing details PubMed
- Josting A, Sieniawski M, Glossmann JP, Staak O, Nogova L, Peters N, Mapara M, Dörken B, Ko Y, Metzner B, Kisro J, Diehl V, Engert A. High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study. Ann Oncol. 2005 Aug;16(8):1359-65. Epub 2005 Jun 6. link to original article contains dosing details in abstract PubMed
DHAP/VIM
DHAP/VIM: Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin) alternating with VP-16 (Etoposide), Ifosfamide, Methotrexate
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Vellenga et al. 2007 (HOVON-44) | 2000-2005 | Phase 3 (C) | R-DHAP/R-VIM | Inferior PFS |
Note: per the paper, "in case patients were non-responsive to DHAP but responsive to VIM, it was allowed to repeat the VIM regimen as the third cycle of reinduction chemotherapy." No statement was made as to whether Mesna was used in the VIM protocol.
Glucocorticoid therapy, DHAP portion (cycles 1 & 3)
- Dexamethasone (Decadron) 40 mg IV or PO once per day on days 1 to 4
Chemotherapy, DHAP portion (cycles 1 & 3)
- Cytarabine (Ara-C) 2000 mg/m2 IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m2)
- Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours, started on day 1
Chemotherapy, VIM portion (cycle 2)
- Etoposide (Vepesid) 90 mg/m2 IV once per day on days 1, 3, 5
- Ifosfamide (Ifex) 1200 mg/m2 IV once per day on days 1 to 5
- Methotrexate (MTX) 30 mg/m2 IV once per day on days 1 & 5
28-day cycle for 3 cycles
Subsequent treatment
- HOVON-44, responders: Stem-cell mobilization, then BEAM with autologous hematopoietic stem cell transplant
References
- HOVON-44: Vellenga E, van Putten WL, van 't Veer MB, Zijlstra JM, Fibbe WE, van Oers MH, Verdonck LF, Wijermans PW, van Imhoff GW, Lugtenburg PJ, Huijgens PC. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood. 2008 Jan 15;111(2):537-43. Epub 2007 Oct 30. link to original article contains dosing details in manuscript PubMed NCT00012051
EPIC (carboplatin)
EPIC: Etoposide, Prednisolone, Ifosfamide, Carboplatin
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Richardson et al. 1994 | 1991-1993 | Phase 2, fewer than 20 patients |
Chemotherapy
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 4
- Ifosfamide (Ifex) 1000 mg/m2 IV once per day on days 1 to 5
- Carboplatin (Paraplatin) 60 mg/m2 IV once on day 10
Glucocorticoid therapy
- Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
Supportive therapy
21-day cycles
References
- Richardson DS, Tighe M, Cull G, Johnson SA, Phillips MJ. Salvage chemotherapy for relapsed and resistant lymphoma with a carboplatin containing schedule--EPIC. Hematol Oncol. 1994 May-Jun;12(3):125-8. link to original article PubMed
EPIC (cisplatin)
EPIC: Etoposide, Prednisolone, Ifosfamide, Cisplatin
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Hickish et al. 1993 | 1989-1991 | Phase 2 |
Chemotherapy
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 4
- Ifosfamide (Ifex) 1000 mg/m2 IV once per day on days 1 to 5
- Cisplatin (Platinol) 60 mg/m2 IV once on day 10
Glucocorticoid therapy
- Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
Supportive therapy
21-day cycles
References
- Hickish T, Roldan A, Cunningham D, Mansi J, Ashley S, Nicolson V, Gore ME, Catovsky D, Smith IE. EPIC: an effective low toxicity regimen for relapsing lymphoma. Br J Cancer. 1993 Sep;68(3):599-604. link to original article link to PMC article contains dosing details in manuscript PubMed
HAM
HAM: High-dose Ara-C (Cytarabine) & Mitoxantrone
NOAC: NOvantrone (Mitoxantrone) & Ara-C (Cytarabine)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Ho et al. 1989 | 1986-1987 | Phase 2 |
Chemotherapy
- Cytarabine (Ara-C) 3000 mg/m2 IV every 12 hours on day 1 (2 doses)
- Mitoxantrone (Novantrone) 10 mg/m2 IV over 15 minutes once per day on days 2 & 3
21-day cycle for 2 cycles
References
- Ho AD, del Valle F, Rückle H, Schwammborn J, Schlimok G, Hiddemann W, Meusers P, Thiel E, Dörken B, Hunstein W. Mitoxantrone and high-dose cytarabine as salvage therapy for refractory non-Hodgkin's lymphoma. Cancer. 1989 Oct 1;64(7):1388-92. link to original article contains dosing details in manuscript PubMed
MINE
MINE: Mesna, Ifosfamide, Novantrone (Mitoxantrone), Etoposide
VIM: Vepesid (Etoposide), Ifosfamide, Mitoxantrone
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Rodriguez et al. 1995 | NR | Phase 2 |
Chemotherapy
- Ifosfamide (Ifex) 1333 mg/m2 IV over 60 minutes once per day on days 1 to 3
- Mitoxantrone (Novantrone) 8 mg/m2 IV once on day 1
- Etoposide (Vepesid) 65 mg/m2 IV over 60 minutes once per day on days 1 to 3
Supportive therapy
- Mesna (Mesnex) 1333 mg/m2 IV over 60 minutes once per day on days 1 to 3
- Mesna (Mesnex) 500 mg PO once, diluted in water or juice, 4 hours following ifosfamide administration
21-day cycles (see below)
Subsequent treatment
- Rodriguez et al. 1995, CR: A total of 6 cycles of MINE, then ESHAP consolidation x 3
- Rodriguez et al. 1995, PR: MINE was given to the point of maximal response, and then patients were crossed over to ESHAP.
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Hopfinger et al. 1995 | 1986-1992 | Phase 2 |
Chemotherapy
- Ifosfamide (Ifex) 650 mg/m2 IV once per day on day 1 to 3
- Mitoxantrone (Novantrone) 3 mg/m2 IV once per day on day 1 to 3
- Etoposide (Vepesid) 65 mg/m2 IV once per day on day 1 to 3
Supportive therapy
- Mesna (Mesnex) 300 mg IV three times per day on days 1 to 3
21-day cycles
References
- Rodriguez MA, Cabanillas FC, Velasquez W, Hagemeister FB, McLaughlin P, Swan F, Romaguera JE. Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP. J Clin Oncol. 1995 Jul;13(7):1734-41. link to original article contains dosing details in manuscript PubMed
- Hopfinger G, Heinz R, Koller E, Schneider B, Pittermann E. Ifosfamide, mitoxantrone and etoposide (VIM) as salvage therapy of low toxicity in non-Hodgkin's lymphoma. Eur J Haematol. 1995 Oct;55(4):223-7. link to original article contains dosing details in manuscript PubMed
VIPD
VIPD: VP-16 (Etoposide), Ifosfamide, Platinol (Cisplatin), Dexamethasone
DVIP: Dexamethasone, VP-16 (Etoposide), Ifosfamide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Haim et al. 1992 | 1989-1991 | Phase 2 |
Glucocorticoid therapy
- Dexamethasone (Decadron) 20 mg IV twice per day on days 1 to 4
Chemotherapy
- Etoposide (Vepesid) 75 mg/m2 IV once per day on days 1 to 4
- Ifosfamide (Ifex) 1200 mg/m2 IV once per day on days 1 to 4
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 4
Supportive therapy
- Mesna (Mesnex) 240 mg IV three times per day on days 1 to 4
21-day cycles
References
- Haim N, Rosenblatt E, Wollner M, Ben-Shahar M, Epelbaum R, Robinson E. Salvage therapy for non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide, and cisplatin. Cancer Chemother Pharmacol. 1992;30(3):243-4. link to original article contains dosing details in manuscript PubMed
Consolidation after salvage therapy
ESHAP
ESHAP: Etoposide, Solumedrol (Methylprednisolone), High dose Ara-C (Cytarabine), Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Rodriguez et al. 1995 | NR | Phase 2 |
Preceding treatment
- MINE salvage induction
Chemotherapy
- Etoposide (Vepesid) 60 mg/m2 IV over 60 minutes once per day on days 1 to 4
- Cytarabine (Ara-C) 2000 mg/m2 IV over 2 hours once on day 5
- Cisplatin (Platinol) 25 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 100 mg/m2)
Glucocorticoid therapy
- Methylprednisolone (Solumedrol) 500 mg IV as a short infusion once per day on days 1 to 4
21-day cycle for 3 cycles
References
- Rodriguez MA, Cabanillas FC, Velasquez W, Hagemeister FB, McLaughlin P, Swan F, Romaguera JE. Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP. J Clin Oncol. 1995 Jul;13(7):1734-41. link to original article contains dosing details in manuscript PubMed
Relapsed or refractory, further lines of therapy
CEPP(B)
CEPP(B): Cyclophosphamide, Etoposide, Procarbazine, Prednisone, (optional) Bleomycin
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Chao et al. 1990 | 1982-1989 | Phase 2 |
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once per day on days 1 & 8
- Etoposide (Vepesid) 70 mg/m2 IV once per day on days 1 to 3
- Procarbazine (Matulane) 60 mg/m2 IV once per day on days 1 to 10
- Bleomycin (Blenoxane) 15 units/m2 (route not specified) once per day on days 1 & 15
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 IV once per day on days 1 to 10
1-month cycles
Dose and schedule modifications
- Cyclophosphamide dose was increased by 50 mg/m2 with each cycle, if prior dose was tolerated
- Etoposide dose was increased by 15 mg/m2 with each cycle, if prior dose was tolerated
References
- Chao NJ, Rosenberg SA, Horning SJ. CEPP(B): an effective and well-tolerated regimen in poor-risk, aggressive non-Hodgkin's lymphoma. Blood. 1990 Oct 1;76(7):1293-8. link to original article contains dosing details in manuscript PubMed
DICE
DICE: Dexamethasone, Ifosfamide, Cisplatin, Etoposide
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Goss et al. 1991 | NR | Phase 2 |
Coleman et al. 2001 | NR in abstract | Phase 2 |
Glucocorticoid therapy
- Dexamethasone (Decadron) 10 mg IV bolus four times per day on days 1 to 4
Chemotherapy
- Ifosfamide (Ifex) 1000 mg/m2 (maximum dose of 1750 mg) IV over 15 to 20 minutes once per day on days 1 to 4
- Cisplatin (Platinol) 25 mg/m2 IV over 60 minutes once per day on days 1 to 4
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 4
Supportive therapy
21- to 28-day cycles
References
- Goss PE, Shepherd FA, Scott JG, Warner E, Baker MA, Sutton D, Farquharson HA, Buick S, Sutcliffe S. Dexamethasone/ifosfamide/cisplatin/etoposide (DICE) as therapy for patients with advanced refractory non-Hodgkin's lymphoma: preliminary report of a phase II study. Ann Oncol. 1991 Jan;2 Suppl 1:43-6. link to original article contains dosing details in abstract PubMed
- Coleman M, Leonard J, Shuster MW, Kaufman TP. DICE (dexamethasone, ifosfamide, cisplatin, etoposide) infusional chemotherapy for refractory or relapsed non-Hodgkin's lymphoma (NHL). Eur J Haematol. 2001 Jul;64:41-5. PubMed
DICEP
DICEP: Dose Intensive Cyclophosphamide, Etoposide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Neidhart et al. 1994 | 1987-1991 | Phase 2 |
Chemotherapy
- Cyclophosphamide (Cytoxan) 2500 mg/m2/day IV on days 1 & 2
- Etoposide (Vepesid) 500 mg/m2/day IV on days 1 to 3
- Cisplatin (Platinol) 50 mg/m2/day IV on days 1 to 3
References
- Neidhart JA, Kubica R, Stidley C, Pfile J, Clark D, Rinehart J. Multiple cycles of dose-intensive cyclophosphamide, etoposide, and cisplatinum (DICEP) produce durable responses in refractory non-Hodgkin's lymphoma. Cancer Invest. 1994;12(1):1-11. link to original article contains dosing details in abstract PubMed
EPOCH
EPOCH: Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
CHEOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Etoposide, Oncovin (Vincristine), Prednisone
Regimen
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Wilson et al. 1993 | 1990-1992 | Phase 2 | ORR: 87% |
Chemotherapy
- Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m2)
- Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m2)
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 6
- Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 PO on days 1 to 6
Supportive therapy
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC >5000/μL past nadir
- PCP prophylaxis with any one of the following:
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day 3 days per week
- Atovaquone (Mepron) 1500 mg PO once per day
- Pentamidine (Nebupent) 300 mg nebulized every 28 days
21-day cycle for 6 to 8 cycles
References
- Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, Kohler DR, Jaffe ES, Herdt J, Cheson BD, Chabner BA. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J Clin Oncol. 1993 Aug;11(8):1573-82. link to original article contains dosing details in manuscript PubMed
- Update: Gutierrez M, Chabner BA, Pearson D, Steinberg SM, Jaffe ES, Cheson BD, Fojo A, Wilson WH. Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas: an 8-year follow-up study of EPOCH. J Clin Oncol. 2000 Nov 1;18(21):3633-42. link to original article PubMed
ESHAP
ESHAP: Etoposide, Solumedrol (Methylprednisolone) High-dose Ara-C (Cytarabine), Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Velasquez et al. 1994 | 1986-1988 | Phase 3 (E-esc) | ESHA | Superior RR |
Avilés et al. 2010 | NR | Phase 3 (C) | R-ESHAP | Did not meet efficacy endpoints |
Note: timing of cycle was variable and dependent on "recovery of the toxic effects"
Chemotherapy
- Etoposide (Vepesid) 40 mg/m2 IV over 60 minutes once per day on days 1 to 4
- Cytarabine (Ara-C) 2000 mg/m2 IV over 2 hours once on day 5
- Cisplatin (Platinol) 25 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 100 mg/m2)
Glucocorticoid therapy
- Methylprednisolone (Solumedrol) 250 to 500 mg IV over 15 minutes once per day on days 1 to 5
Supportive therapy
- At least 1 liter normal saline with 25 to 50 g Mannitol once per day throughout chemotherapy
- Metoclopramide (Reglan) 0.5 to 1 mg/kg (route not specified) "given regularly"
21- to 28-day cycle for 6 to 8 cycles
References
- Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. link to original article contains dosing details in manuscript PubMed
- Avilés A, Neri N, Huerta-Guzmán J, de Jesús Nambo M. ESHAP versus rituximab-ESHAP in frail patients with refractory diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2010 Apr;10(2):125-8. link to original article PubMed
Etoposide, Ifosfamide, Methotrexate
IMVP-16: Ifosfamide, Methotrexate, VP-16 (Etoposide)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Cabanillas et al. 1982 | NR | Phase 2 |
Chemotherapy
- Ifosfamide (Ifex) 1000 mg/m2 IV over 60 minutes once per day on days 1 to 5
- Methotrexate (MTX) 30 mg/m2 (route not specified) once per day on days 3 & 10
- Etoposide (Vepesid) 100 mg/m2 IV over 2 hours once per day on days 1 to 3
21-day cycles
References
- Cabanillas F, Hagemeister FB, Bodey GP, Freireich EJ. IMVP-16: an effective regimen for patients with lymphoma who have relapsed after initial combination chemotherapy. Blood. 1982 Sep;60(3):693-7. link to original article contains dosing details in manuscript PubMed
GDP
GDP: Gemcitabine, Dexamethasone, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Crump et al. 2004 | 2001-2002 | Phase 2 |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
- Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 1
Glucocorticoid therapy
- Dexamethasone (Decadron) 40 mg IV or PO once per day on days 1 to 4
21-day cycle for up to 6 cycles
References
- Crump M, Baetz T, Couban S, Belch A, Marcellus D, Howson-Jan K, Imrie K, Myers R, Adams G, Ding K, Paul N, Shepherd L, Iglesias J, Meyer R; National Cancer Institute of Canada Clinical Trials Group. Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). Cancer. 2004 Oct 15;101(8):1835-42. link to original article PubMed
ICE
ICE: Ifosfamide, Carboplatin, Etoposide
Regimen variant #1, inpatient
Study | Dates of enrollment | Evidence |
---|---|---|
Moskowitz et al. 1999 | 1993-1997 | Phase 2 |
Zelenetz et al. 2003 | 1993-2000 | Phase 2 |
Note: Third cycle was intended to be followed by peripheral blood hematopoietic cell collection. Carboplatin AUC was calculated based on a 12-hour creatinine clearance.
Chemotherapy
- Ifosfamide (Ifex) 5000 mg/m2 IV continuous infusion over 24 hours, started on day 2, mixed with mesna
- Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg) IV bolus once on day 2
- Etoposide (Vepesid) 100 mg/m2 IV bolus once per day on days 1 to 3
Supportive therapy
- Mesna (Mesnex) 5000 mg/m2 IV continuous infusion over 24 hours, started on day 2, mixed with ifosfamide
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 5 to 12 (10 mcg/kg with cycle 3, given until collection of peripheral blood hematopoietic cells)
14-day cycle for 3 cycles; treatment can be delayed until ANC is greater than 1000/μL and platelet count greater than 50 x 109/L
Regimen variant #2, outpatient
Study | Dates of enrollment | Evidence |
---|---|---|
Hertzberg et al. 2003 | NR | Phase 2, fewer than 20 pts in this subgroup |
Note: Third cycle was intended to be followed by peripheral blood hematopoietic cell collection
Chemotherapy
- Ifosfamide (Ifex) 1667 mg/m2 IV over 2 hours once per day on days 1 to 3, mixed with mesna
- Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg) IV over 60 minutes once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV over 30 minutes once per day on days 1 to 3
Supportive therapy
- Mesna (Mesnex) 1667 mg/m2 IV over 2 hours once per day on days 1 to 3, mixed with ifosfamide
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, started on day 5
21-day cycle for 3 cycles
References
- Moskowitz CH, Bertino JR, Glassman JR, Hedrick EE, Hunte S, Coady-Lyons N, Agus DB, Goy A, Jurcic J, Noy A, O'Brien J, Portlock CS, Straus DS, Childs B, Frank R, Yahalom J, Filippa D, Louie D, Nimer SD, Zelenetz AD. Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3776-85. link to original article contains dosing details in manuscript PubMed
- Zelenetz AD, Hamlin P, Kewalramani T, Yahalom J, Nimer S, Moskowitz CH. Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003;14 Suppl 1:i5-10. link to original article contains dosing details in manuscript PubMed
- Hertzberg MS, Crombie C, Benson W, Taper J, Gottlieb D, Bradstock KF. Outpatient-based ifosfamide, carboplatin and etoposide (ICE) chemotherapy in transplant-eligible patients with non-Hodgkin's lymphoma and Hodgkin's disease. Ann Oncol. 2003;14 Suppl 1:i11-6. link to original article contains dosing details in manuscript PubMed
R-INO
R-INO: Rituximab, INOtuzumab ozogamicin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fayad et al. 2013 (B1931004) | 2006-NR | Phase 1/2 | ||
Dang et al. 2017 (B1931008) | 2011-2013 | Phase 3 (E-switch-ooc) | Investigator's choice of: 1a. BR 1b. Gemcitabine & Rituximab |
Did not meet primary endpoint of OS Median OS: 9.5 vs 9.5 mo (HR 1.1, 95% CI 0.8-1.4) |
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Antibody-drug conjugate therapy
- Inotuzumab ozogamicin (Besponsa) 1.8 mg/m2 IV once on day 2
28-day cycle for up to 8 cycles
References
- B1931004: Fayad L, Offner F, Smith MR, Verhoef G, Johnson P, Kaufman JL, Rohatiner A, Advani A, Foran J, Hess G, Coiffier B, Czuczman M, Giné E, Durrant S, Kneissl M, Luu KT, Hua SY, Boni J, Vandendries E, Dang NH. Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab. J Clin Oncol. 2013 Feb 10;31(5):573-83. Epub 2013 Jan 7. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00299494
- B1931008: Dang NH, Ogura M, Castaigne S, Fayad LE, Jerkeman M, Radford J, Pezzutto A, Bondarenko I, Stewart DA, Shnaidman M, Sullivan S, Vandendries E, Tobinai K, Ramchandren R, Hamlin PA, Giné E, Ando K. Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab versus chemotherapy plus rituximab for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2018 Aug;182(4):583-586. Epub 2017 Jul 5. link to original article link to PMC article contains dosing details in abstract PubMed NCT01232556