Difference between revisions of "Diffuse large B-cell lymphoma"

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''Recommended "to improve the performance status of patients and to ameliorate side-effects of the first chemotherapy cycle."''
 
''Recommended "to improve the performance status of patients and to ameliorate side-effects of the first chemotherapy cycle."''
−
 
+
====Chemotherapy====
 
*[[Vincristine (Oncovin)]] 1 mg IV once (day not specified)
 
*[[Vincristine (Oncovin)]] 1 mg IV once (day not specified)
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 7
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 7
Line 100: Line 100:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Doxorubicin (Adriamycin)]] 75 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV once on day 1
−
*[[Vindesine (Eldisine)]] 2 mg/m2 IV once per day on days 1 & 5
+
*[[Vindesine (Eldisine)]] 2 mg/m<sup>2</sup> IV once per day on days 1 & 5
 
*[[Bleomycin (Blenoxane)]] 10 units IV once per day on days 1 & 5
 
*[[Bleomycin (Blenoxane)]] 10 units IV once per day on days 1 & 5
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO once per day on days 1 to 5
+
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 5
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
  
−
CNS prophylaxis:
+
====CNS prophylaxis====
 
*[[Methotrexate (MTX)]] 15 mg intrathecal on day 1
 
*[[Methotrexate (MTX)]] 15 mg intrathecal on day 1
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Filgrastim (Neupogen)]] 300 mcg (for patients <75 kg) or 480 mcg (for patients ≥75 kg) SC once per day on days 6 to 13
 
*[[Filgrastim (Neupogen)]] 300 mcg (for patients <75 kg) or 480 mcg (for patients ≥75 kg) SC once per day on days 6 to 13
  
−
'''14-day cycle x 4 cycles'''  
+
'''14-day cycle for 4 cycles'''  
  
 
''Treatment followed in 4 weeks by [[#Methotrexate_.28MTX.29|methotrexate consolidation]].''
 
''Treatment followed in 4 weeks by [[#Methotrexate_.28MTX.29|methotrexate consolidation]].''
Line 167: Line 167:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV over 15 minutes once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 15 minutes once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV bolus over 1 to 2 minutes once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV bolus over 1 to 2 minutes once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV bolus over 1 to 2 minutes once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV bolus over 1 to 2 minutes once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
  
−
'''21-day cycle x 8 cycles'''
+
'''21-day cycle for 8 cycles'''
  
 
===Regimen #2 {{#subobject:9e770b|Variant=1}}===
 
===Regimen #2 {{#subobject:9e770b|Variant=1}}===
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|}
 
|}
 
''Treatment in '''NHL-B2''' preceded by [[#Vincristine_.26_Prednisone|pre-phase vincristine & prednisone]].''
 
''Treatment in '''NHL-B2''' preceded by [[#Vincristine_.26_Prednisone|pre-phase vincristine & prednisone]].''
−
 
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
Line 219: Line 219:
 
*At the discretion of ordering physician: [[Filgrastim (Neupogen)]] 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13  
 
*At the discretion of ordering physician: [[Filgrastim (Neupogen)]] 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13  
  
−
'''21-day cycle x 6 cycles'''
+
'''21-day cycle for 6 cycles'''
  
 
====Radiation therapy for initial bulky disease (NHL-B2)====
 
====Radiation therapy for initial bulky disease (NHL-B2)====
Line 250: Line 250:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV over 15 minutes once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 15 minutes once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV bolus over 1 to 2 minutes once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV bolus over 1 to 2 minutes once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV bolus over 1 to 2 minutes once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV bolus over 1 to 2 minutes once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
  
−
'''21-day cycle x 3 cycles''', then followed by radiation therapy
+
'''21-day cycle for 3 cycles''', then followed by radiation therapy
  
 
Radiation therapy, starting 3 weeks after cycle 3 of CHOP:
 
Radiation therapy, starting 3 weeks after cycle 3 of CHOP:
Line 286: Line 286:
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 +
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
====Supportive medications====
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
 
−
*[[Prednisone (Sterapred)]] 40 mg/m2 PO once per day on days 1 to 5
 
−
 
 
−
Supportive medications:
 
 
*[[Filgrastim (Neupogen)]] used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
 
*[[Filgrastim (Neupogen)]] used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
  
−
'''21-day cycle x 8 cycles'''
+
'''21-day cycle for 8 cycles'''
  
 
===Regimen #5 {{#subobject:5b37b5|Variant=1}}===
 
===Regimen #5 {{#subobject:5b37b5|Variant=1}}===
Line 320: Line 320:
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 +
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose per cycle: 2 mg) IV once on day 1
 +
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
====Supportive medications====
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose per cycle: 2 mg) IV once on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg/m2 PO once per day on days 1 to 5
 
−
 
 
−
Supportive medications:
 
 
*[[Filgrastim (Neupogen)]] "recommended according to guidelines"
 
*[[Filgrastim (Neupogen)]] "recommended according to guidelines"
  
−
'''21-day cycle x 6 to 8 cycles'''
+
'''21-day cycle for 6 to 8 cycles'''
  
 
''Patients with CR/PR proceeded to receive [[#Rituximab_.28Rituxan.29|maintenance rituximab]] versus [[#Observation|observation]].''
 
''Patients with CR/PR proceeded to receive [[#Rituximab_.28Rituxan.29|maintenance rituximab]] versus [[#Observation|observation]].''
Line 345: Line 345:
 
## '''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. [http://jco.ascopubs.org/content/23/18/4117.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/23/18/4117.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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://bloodjournal.hematologylibrary.org/content/116/12/2040.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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. [http://bloodjournal.hematologylibrary.org/content/116/12/2040.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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 (GELA). 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. [http://www.sciencedirect.com/science/article/pii/S2152265011006070 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/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 (GELA). 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. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00607-0/fulltext link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/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 verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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 verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12920037 PubMed]
 
# 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. [http://bloodjournal.hematologylibrary.org/content/104/3/626.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14982884 PubMed]
 
# 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. [http://bloodjournal.hematologylibrary.org/content/104/3/626.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14982884 PubMed]
Line 384: Line 384:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 1600 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 1600 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 65 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 65 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 2 to 11, or until ANC is greater than 10,000
 
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 2 to 11, or until ANC is greater than 10,000
  
−
'''14-day cycles x up to 6 cycles'''
+
'''14-day cycle for up to 6 cycles'''
  
 
===Regimen #2 {{#subobject:d78eb4|Variant=1}}===
 
===Regimen #2 {{#subobject:d78eb4|Variant=1}}===
Line 411: Line 411:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 70 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 70 mg/m<sup>2</sup> IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 2 to 11
 
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 2 to 11
  
−
'''14-day cycles x 6 cycles'''
+
'''14-day cycle for 6 cycles'''
  
 
===Regimen #3 {{#subobject:22ca16|Variant=1}}===
 
===Regimen #3 {{#subobject:22ca16|Variant=1}}===
Line 456: Line 456:
  
 
====Main CHOP-14 regimen====
 
====Main CHOP-14 regimen====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
Line 464: Line 464:
 
*[[Filgrastim (Neupogen)]] 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13
 
*[[Filgrastim (Neupogen)]] 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13
  
−
'''14-day cycles x 6 cycles'''; some patients in Pfreundschuh et al. 2008 received 14-day cycles x 8 cycles
+
'''14-day cycle for 6 cycles'''; some patients in Pfreundschuh et al. 2008 received 14-day cycle for 8 cycles
  
 
====Radiation therapy for initial bulky disease====
 
====Radiation therapy for initial bulky disease====
Line 509: Line 509:
 
|}
 
|}
 
''This regimen is designed for elderly patients and is of lower intensity than standard CHOP.''
 
''This regimen is designed for elderly patients and is of lower intensity than standard CHOP.''
−
 
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 30 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once on day 1
 
*[[Vincristine (Oncovin)]] 1 mg IV once on day 1
 
*[[Vincristine (Oncovin)]] 1 mg IV once on day 1
 
*[[Prednisolone (Millipred)]] 20 mg PO BID on days 1 to 5
 
*[[Prednisolone (Millipred)]] 20 mg PO BID on days 1 to 5
  
−
'''21-day cycles x 6 cycles'''
+
'''21-day cycle for 6 cycles'''
  
 
===References===
 
===References===
Line 569: Line 569:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV once on day 1
+
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 1
 
*[[Vincristine (Oncovin)]] 1 mg IV once on day 1
 
*[[Vincristine (Oncovin)]] 1 mg IV once on day 1
 
*[[Prednisolone (Millipred)]] 20 mg PO BID on days 1 to 5
 
*[[Prednisolone (Millipred)]] 20 mg PO BID on days 1 to 5
  
−
'''21-day cycles x 6 cycles'''
+
'''21-day cycle for 6 cycles'''
  
 
===References===
 
===References===
Line 619: Line 619:
 
|-
 
|-
 
|}
 
|}
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 0 (cycles 1 to 4, 6, and 8)
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 0 (cycles 1 to 4, 6, and 8)
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 +
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg 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
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
  
−
'''14-day cycle x 8 cycles'''
+
'''14-day cycle for 8 cycles'''
  
 
====Radiotherapy====
 
====Radiotherapy====
Line 645: Line 646:
 
|-
 
|-
 
|}
 
|}
−
 
+
====R-CHOEP portion====
−
====R-CHOEP====
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
−
*[[Etoposide (Vepesid)]] 100 mg/m2 IV once per day on days 1 to 3
 
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day from day 4 or [[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 4
 
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day from day 4 or [[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 4
  
−
'''14-day cycle x 8 cycles, followed by:'''
+
'''14-day cycle for 8 cycles, followed by:'''
  
 
====CNS Prophylaxis====
 
====CNS Prophylaxis====
 
''Note that IT treatment was not part of prophylaxis, except that [[Methotrexate (MTX)]] 15 mg IT was allowed at time of diagnostic LP.''
 
''Note that IT treatment was not part of prophylaxis, except that [[Methotrexate (MTX)]] 15 mg IT was allowed at time of diagnostic LP.''
  
−
*[[Cytarabine (Cytosar)]] 3000 mg/m2 IV BID for 2 days (4 doses)
+
====HiDAC portion====
−
**Dose reduced to 2000 mg/m2 for patients aged 60-65 years
+
*[[Cytarabine (Cytosar)]] 3000 mg/m<sup>2</sup> IV BID for 2 days (4 doses)
 +
**Dose reduced to 2000 mg/m<sup>2</sup> for patients aged 60-65 years
  
 
'''Followed 3 weeks later by:'''
 
'''Followed 3 weeks later by:'''
  
−
*[[Methotrexate (MTX)]] 3000 mg/m2 IV continuous infusion over 24 hours
+
====HD-MTX portion====
 +
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV continuous infusion over 24 hours
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Folinic acid (Leucovorin)]] (dose/frequency not specified) starting at 36 hours
 
*[[Folinic acid (Leucovorin)]] (dose/frequency not specified) starting at 36 hours
  
Line 696: Line 698:
 
‘’Note: most of the variation between these regimen variants is in the dose or type of steroid.’’
 
‘’Note: most of the variation between these regimen variants is in the dose or type of steroid.’’
  
−
===Regimen #1, prednisone 100 mg/m2 {{#subobject:e3dfe2|Variant=1}}===
+
===Regimen #1, prednisone 100 mg/m<sup>2</sup> {{#subobject:e3dfe2|Variant=1}}===
 
{| border="1" style="text-align:center;" !align="left"  
 
{| border="1" style="text-align:center;" !align="left"  
 
|'''Study'''
 
|'''Study'''
Line 721: Line 723:
  
 
''This regimen was used for non-germinal center B-cell (non-GCB) DLBCL.''
 
''This regimen was used for non-germinal center B-cell (non-GCB) DLBCL.''
 +
====Chemotherapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 +
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
 +
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
'''21-day cycle for 6 cycles'''
−
*[[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 per cycle) IV once on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg/m2 PO once per day on days 1 to 5
 
  
−
'''21-day cycle x 6 cycles'''
+
===Regimen #2, prednisone 40 mg/m<sup>2</sup> {{#subobject:a326e|Variant=1}}===
−
 
 
−
===Regimen #2, prednisone 40 mg/m2 {{#subobject:a326e|Variant=1}}===
 
 
{| border="1" style="text-align:center;" !align="left"  
 
{| border="1" style="text-align:center;" !align="left"  
 
|'''Study'''
 
|'''Study'''
Line 768: Line 770:
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 +
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
====CNS prophylaxis====
−
*[[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 per cycle) IV once on day 1
 
−
*[[Prednisone (Sterapred)]] 40 mg/m2 PO once per day on days 1 to 5
 
−
 
 
−
CNS prophylaxis:
 
 
As described in Delarue et al. 2013 (LNH03-6B):
 
As described in Delarue et al. 2013 (LNH03-6B):
 
*[[Methotrexate (MTX)]] 15 mg IT once every 21 days x 4 total doses
 
*[[Methotrexate (MTX)]] 15 mg IT once every 21 days x 4 total doses
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Filgrastim (Neupogen)]] used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
 
*[[Filgrastim (Neupogen)]] used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
  
−
'''21-day cycle x 8 cycles'''
+
'''21-day cycle for 8 cycles'''
  
 
===Regimen #3, prednisone 100 mg, flat-dose vincristine {{#subobject:bcb2bf|Variant=1}}===
 
===Regimen #3, prednisone 100 mg, flat-dose vincristine {{#subobject:bcb2bf|Variant=1}}===
Line 814: Line 816:
 
|-
 
|-
 
|}
 
|}
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 +
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*Radiation therapy: 30 to 40 Gy given to sites of primary bulky disease; 30 to 40 Gy to primary extranodal disease at physician discretion
 
*Radiation therapy: 30 to 40 Gy given to sites of primary bulky disease; 30 to 40 Gy to primary extranodal disease at physician discretion
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Filgrastim (Neupogen)]] or [[Lenograstim (Granocyte)]] used at physician discretion for neutropenia
 
*[[Filgrastim (Neupogen)]] or [[Lenograstim (Granocyte)]] used at physician discretion for neutropenia
  
−
'''21-day cycle x 6 cycles'''
+
'''21-day cycle for 6 cycles'''
  
 
===Regimen #4, rituximab lead-in {{#subobject:f05383|Variant=1}}===
 
===Regimen #4, rituximab lead-in {{#subobject:f05383|Variant=1}}===
Line 849: Line 852:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Rituximab (Rituxan)]] as follows:
 
*[[Rituximab (Rituxan)]] as follows:
−
**Cycle 1: 375 mg/m2 IV once per day on days -7 & -3  
+
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days -7 & -3  
−
**Cycle 2 onwards: 375 mg/m2 IV once on day -2
+
**Cycle 2 onwards: 375 mg/m<sup>2</sup> IV once on day -2
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose per cycle: 2 mg) IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose per cycle: 2 mg) IV once on day 1
−
*[[Prednisone (Sterapred)]] 100 mg/m2 PO once per day on days 1 to 5
+
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Filgrastim (Neupogen)]] "recommended according to guidelines"
 
*[[Filgrastim (Neupogen)]] "recommended according to guidelines"
  
−
'''21-day cycle x 6 to 8 cycles'''
+
'''21-day cycle for 6 to 8 cycles'''
  
 
''This trial also included a randomization to [[Diffuse_large_B-cell_lymphoma#Rituximab_.28Rituxan.29|maintenance rituximab]] versus [[Diffuse_large_B-cell_lymphoma#Observation|observation]] for responders; however an advantage was only seen in the group receiving [[Diffuse_large_B-cell_lymphoma#CHOP|CHOP]] upfront, which is no longer standard of care.''
 
''This trial also included a randomization to [[Diffuse_large_B-cell_lymphoma#Rituximab_.28Rituxan.29|maintenance rituximab]] versus [[Diffuse_large_B-cell_lymphoma#Observation|observation]] for responders; however an advantage was only seen in the group receiving [[Diffuse_large_B-cell_lymphoma#CHOP|CHOP]] upfront, which is no longer standard of care.''
Line 888: Line 891:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO/IV once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO/IV once per day on days 1 to 5
  
−
Supportive medications:
+
====Supportive medications====
 
*Prophylactic [[Filgrastim (Neupogen)|G-CSF]] used for persisting grade 4 neutropenia or febrile neutropenia.
 
*Prophylactic [[Filgrastim (Neupogen)|G-CSF]] used for persisting grade 4 neutropenia or febrile neutropenia.
 
*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] (dose/schedule not specified) prophylaxis.
 
*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] (dose/schedule not specified) prophylaxis.
 
*Erythropoietin use was allowed for hemoglobin <11 g/dL.
 
*Erythropoietin use was allowed for hemoglobin <11 g/dL.
  
−
'''21-day cycle x 6 cycles'''
+
'''21-day cycle for 6 cycles'''
  
 
====Radiation therapy====
 
====Radiation therapy====
 
''"At the end of chemotherapy, radiotherapy (RT) was scheduled for sites of previous bulky disease or partially responding sites."''
 
''"At the end of chemotherapy, radiotherapy (RT) was scheduled for sites of previous bulky disease or partially responding sites."''
  
−
===Regimen #6, prednisolone 40 mg/m2 {{#subobject:74f424|Variant=1}}===
+
===Regimen #6, prednisolone 40 mg/m<sup>2</sup> {{#subobject:74f424|Variant=1}}===
 
{| border="1" style="text-align:center;" !align="left"  
 
{| border="1" style="text-align:center;" !align="left"  
 
|'''Study'''
 
|'''Study'''
Line 928: Line 931:
 
|-
 
|-
 
|}
 
|}
−
 
 
''Note: Cunningham et al. 2013 said that it based its regimen on Coiffier et al. 2002, but notably it uses prednisolone instead of prednisone.''
 
''Note: Cunningham et al. 2013 said that it based its regimen on Coiffier et al. 2002, but notably it uses prednisolone instead of prednisone.''
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Prednisolone (Millipred)]] 40 mg/m2 PO once per day on days 1 to 5
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
 +
*[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
CNS prophylaxis:
+
====CNS prophylaxis====
 
Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:
 
Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:
 
*[[Methotrexate (MTX)]] 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines."  No other details given.
 
*[[Methotrexate (MTX)]] 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines."  No other details given.
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12 at physician discretion
 
*[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12 at physician discretion
 
*[[Allopurinol (Zyloprim)]] 300 mg PO once per day during cycle 1
 
*[[Allopurinol (Zyloprim)]] 300 mg PO once per day during cycle 1
 
*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Co-trimoxazole]] 480 mg (route not specified) BID on 3 days per week, taken throughout therapy, ending 2 weeks after chemotherapy is completed
 
*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Co-trimoxazole]] 480 mg (route not specified) BID on 3 days per week, taken throughout therapy, ending 2 weeks after chemotherapy is completed
  
−
'''21-day cycle x 8 cycles'''
+
'''21-day cycle for 8 cycles'''
  
 
===Regimen #7, short-course for early stage DLBCL {{#subobject:caca45|Variant=1}}===
 
===Regimen #7, short-course for early stage DLBCL {{#subobject:caca45|Variant=1}}===
Line 963: Line 966:
  
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on days -7, 1, 22, 43 (4 doses total)
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on days -7, 1, 22, 43 (4 doses total)
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
  
−
'''21-day cycle x 3 cycles, followed by:'''
+
'''21-day cycle for 3 cycles, followed by:'''
  
 
====Radiation therapy====
 
====Radiation therapy====
Line 992: Line 995:
  
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 0 or 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 0 or 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
  
−
CNS Prophylaxis:
+
====CNS prophylaxis====
 
*[[Methotrexate (MTX)]] 12 mg IT once per week x 4 total doses
 
*[[Methotrexate (MTX)]] 12 mg IT once per week x 4 total doses
  
−
'''21-day cycle x 6 cycles (up to 8 cycles for stage II patients), followed by:'''
+
'''21-day cycle for 6 cycles (up to 8 cycles for stage II patients), followed by:'''
  
 
====Radiation therapy====
 
====Radiation therapy====
Line 1,010: Line 1,013:
 
## '''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. [http://jco.ascopubs.org/content/23/18/4117.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/23/18/4117.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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://bloodjournal.hematologylibrary.org/content/116/12/2040.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20548096 PubMed] content property of [http://hemonc.org HemOnc.org]
 
## '''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://bloodjournal.hematologylibrary.org/content/116/12/2040.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20548096 PubMed] content property of [http://hemonc.org HemOnc.org]
−
## '''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 (GELA). 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. [http://www.sciencedirect.com/science/article/pii/S2152265011006070 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/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 (GELA). 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. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00607-0/fulltext link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/22301063 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970664-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970664-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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 (MInT) 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2811%2970235-2/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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 (MInT) 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2811%2970235-2/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21940214 PubMed]
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|}
 
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−
====Main CHOP-14 regimen====
+
====Main CHOP-14 portion====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
  
−
====Rituximab====
+
====Rituximab portion====
 
''Two arms were assessed; results are pending from this comparison. These higher doses were for males, only.''
 
''Two arms were assessed; results are pending from this comparison. These higher doses were for males, only.''
−
*[[Rituximab (Rituxan)]] 500 mg/m2 IV once every two weeks
+
*[[Rituximab (Rituxan)]] 500 mg/m<sup>2</sup> IV once every two weeks
 
OR
 
OR
−
*[[Rituximab (Rituxan)]] 500 mg/m2 IV once on days -1, 0, 3, 7, 14, 21, 28, 42
+
*[[Rituximab (Rituxan)]] 500 mg/m<sup>2</sup> IV once on days -1, 0, 3, 7, 14, 21, 28, 42
  
−
'''14-day cycles x 6 cycles (8 doses of rituximab regardless of total number of CHOP-14 cycles)'''
+
'''14-day cycle for 6 cycles (8 doses of rituximab regardless of total number of CHOP-14 cycles)'''
  
 
===Regimen #2 {{#subobject:6ec36f|Variant=1}}===
 
===Regimen #2 {{#subobject:6ec36f|Variant=1}}===
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|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 +
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
====CNS prophylaxis====
−
*[[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
 
−
*[[Prednisone (Sterapred)]] 40 mg/m2 PO once per day on days 1 to 5
 
−
 
 
−
CNS prophylaxis:
 
 
*[[Methotrexate (MTX)]] 15 mg IT once every 14 days x 4 total doses
 
*[[Methotrexate (MTX)]] 15 mg IT once every 14 days x 4 total doses
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Filgrastim (Neupogen)|Granulocyte colony-stimulating factor]] or [[Pegfilgrastim (Neulasta)|pegylated G-CSF]] "according to the treating doctor's decision, fulfilling existing guidelines and product labelling at that time."
 
*[[Filgrastim (Neupogen)|Granulocyte colony-stimulating factor]] or [[Pegfilgrastim (Neulasta)|pegylated G-CSF]] "according to the treating doctor's decision, fulfilling existing guidelines and product labelling at that time."
  
−
'''14-day cycles x 8 cycles'''
+
'''14-day cycle for 8 cycles'''
  
 
===Regimen #3 {{#subobject:8136b1|Variant=1}}===
 
===Regimen #3 {{#subobject:8136b1|Variant=1}}===
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|-
 
|-
 
|}
 
|}
−
====Main R-CHOP-14 regimen====
+
====Main R-CHOP-14 portion====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Prednisolone (Millipred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisolone (Millipred)]] 100 mg PO once per day on days 1 to 5
  
−
CNS prophylaxis:
+
====CNS prophylaxis====
 
Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:
 
Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:
 
*[[Methotrexate (MTX)]] 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines."  No other details given.
 
*[[Methotrexate (MTX)]] 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines."  No other details given.
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12
 
*[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12
 
*Allopurinol (Aloprim) 300 mg PO once per day during cycle 1
 
*Allopurinol (Aloprim) 300 mg PO once per day during cycle 1
 
*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Co-trimoxazole]] 480 mg (route not specified) BID on 3 days per week, taken throughout therapy, ending 2 weeks after treatment is completed
 
*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Co-trimoxazole]] 480 mg (route not specified) BID on 3 days per week, taken throughout therapy, ending 2 weeks after treatment is completed
  
−
'''14-day cycles x 6 cycles; then give additional doses of rituximab as described below'''
+
'''14-day cycle for 6 cycles; then give additional doses of rituximab as described below'''
  
 
====Additional doses of Rituximab====
 
====Additional doses of Rituximab====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
  
−
'''14-day cycles x 2 cycles'''
+
'''14-day cycle for 2 cycles'''
  
 
===Regimen #4 {{#subobject:30c25c|Variant=1}}===
 
===Regimen #4 {{#subobject:30c25c|Variant=1}}===
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====Main regimen====
 
====Main regimen====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Filgrastim (Neupogen)]] or [[Lenograstim (Granocyte)]] (dose/route/frequency not specified) starting on day 4, to continue until count recovery  
 
*[[Filgrastim (Neupogen)]] or [[Lenograstim (Granocyte)]] (dose/route/frequency not specified) starting on day 4, to continue until count recovery  
  
−
'''14-day cycles x 6 to 8 cycles (8 doses of rituximab regardless of total number of cycles)'''
+
'''14-day cycle for 6 to 8 cycles (8 doses of rituximab regardless of total number of cycles)'''
  
 
====Radiation therapy for initial bulky disease====
 
====Radiation therapy for initial bulky disease====
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====Main regimen====
 
====Main regimen====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on days -4, 0, 10, 29, 57, 99, 155, and 239 (independent of CHOP cycles)
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on days -4, 0, 10, 29, 57, 99, 155, and 239 (independent of CHOP cycles)
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Filgrastim (Neupogen)]] or [[Lenograstim (Granocyte)]] (dose/route/frequency not specified) starting on day 4, to continue until count recovery  
 
*[[Filgrastim (Neupogen)]] or [[Lenograstim (Granocyte)]] (dose/route/frequency not specified) starting on day 4, to continue until count recovery  
  
−
'''14-day cycles x 6 cycles'''
+
'''14-day cycle for 6 cycles'''
  
 
====Radiation therapy for initial bulky disease====
 
====Radiation therapy for initial bulky disease====
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===Regimen {{#subobject:1593ec|Variant=1}}===
 
===Regimen {{#subobject:1593ec|Variant=1}}===
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Prednisone (Sterapred)]] 40 mg/m2 PO once per day on days 1 to 5
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
'''21-day cycles x up to 8 cycles'''
+
'''21-day cycle for up to 8 cycles'''
  
 
===References===
 
===References===
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====Part A (cycles 1, 3, 5)====
 
====Part A (cycles 1, 3, 5)====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m2 IV Q12H on days 1 to 3 (6 total doses)
+
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV Q12H on days 1 to 3 (6 total doses)
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg) IV once per day on days 5 & 12
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 5 & 12
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 5  
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 5  
 
*[[Dexamethasone (Decadron)]] 40 mg PO/IV once per day on days 2 to 5
 
*[[Dexamethasone (Decadron)]] 40 mg PO/IV once per day on days 2 to 5
  
−
Supportive care:
+
====Supportive medications====
−
*[[Mesna (Mesnex)]] 600 mg/m2/day IV continuous infusion on days 1 to 3
+
*[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 3
 
*[[Filgrastim (Neupogen)]] or [[Pegfilgrastim (Neulasta)]] starting 24 to 48 hours after completion of chemotherapy
 
*[[Filgrastim (Neupogen)]] or [[Pegfilgrastim (Neulasta)]] starting 24 to 48 hours after completion of chemotherapy
 
*[[Ciprofloxacin (Cipro)]] 500 mg PO BID for 10 days after chemotherapy
 
*[[Ciprofloxacin (Cipro)]] 500 mg PO BID for 10 days after chemotherapy
Line 1,313: Line 1,317:
 
*[[Valacyclovir (Valtrex)]] 500 mg PO once per day for 10 days after chemotherapy
 
*[[Valacyclovir (Valtrex)]] 500 mg PO once per day for 10 days after chemotherapy
  
−
Dose modifications:
+
====Dose modifications====
 
*[[Vincristine (Oncovin)]] reduced once by 50% for NCI common toxicity criteria Grade 2+ peripheral neuropathy, omitted if Grade 2+ peripheral neuropathy persists
 
*[[Vincristine (Oncovin)]] reduced once by 50% for NCI common toxicity criteria Grade 2+ peripheral neuropathy, omitted if Grade 2+ peripheral neuropathy persists
 
*[[Doxorubicin (Adriamycin)]] and [[Cyclophosphamide (Cytoxan)]] reduced by 20% in subsequent A cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC <0.75 × 10^9/L or platelet count <75 × 10^9/L on day 21  
 
*[[Doxorubicin (Adriamycin)]] and [[Cyclophosphamide (Cytoxan)]] reduced by 20% in subsequent A cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC <0.75 × 10^9/L or platelet count <75 × 10^9/L on day 21  
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====Part B (cycles 2, 4, 6)====
 
====Part B (cycles 2, 4, 6)====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Methotrexate (MTX)]] 200 mg/m2 IV over 2 hours then 800 mg/m2 IV over 22 hours on day 1
+
*[[Methotrexate (MTX)]] 200 mg/m<sup>2</sup> IV over 2 hours then 800 mg/m<sup>2</sup> IV over 22 hours on day 1
−
*[[Cytarabine (Cytosar)]] 3000 mg/m2 IV over 2 hours Q12H on days 3 & 4 (4 total doses)
+
*[[Cytarabine (Cytosar)]] 3000 mg/m<sup>2</sup> IV over 2 hours Q12H on days 3 & 4 (4 total doses)
  
−
Supportive care:
+
====Supportive medications====
 
*[[Folinic acid (Leucovorin)]] (dose/timing not specified) until serum methotrexate level <0.1 µM
 
*[[Folinic acid (Leucovorin)]] (dose/timing not specified) until serum methotrexate level <0.1 µM
 
*[[Sodium bicarbonate]] 1300 mg PO BID until methotrexate level <0.1 µM
 
*[[Sodium bicarbonate]] 1300 mg PO BID until methotrexate level <0.1 µM
Line 1,334: Line 1,338:
 
*[[Valacyclovir (Valtrex)]] 500 mg PO once per day for 10 days after chemotherapy
 
*[[Valacyclovir (Valtrex)]] 500 mg PO once per day for 10 days after chemotherapy
  
−
Dose modifications:
+
====Dose modifications====
 
*[[Methotrexate (MTX)]] reduced by 25% in subsequent B cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC < 0.75 × 10^9/L or platelet count < 75 × 10^9/L on day 21
 
*[[Methotrexate (MTX)]] reduced by 25% in subsequent B cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC < 0.75 × 10^9/L or platelet count < 75 × 10^9/L on day 21
 
*[[Cytarabine (Cytosar)]] reduced by 33% in subsequent B cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC < 0.75 × 10^9/L or platelet count < 75 × 10^9/L on day 21
 
*[[Cytarabine (Cytosar)]] reduced by 33% in subsequent B cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC < 0.75 × 10^9/L or platelet count < 75 × 10^9/L on day 21
Line 1,340: Line 1,344:
 
'''21-day cycles'''
 
'''21-day cycles'''
  
−
CNS prophylaxis: ''"recommended in patients with paraspinal disease, paranasal sinus disease, testicular disease, bone marrow disease, diffuse osseous disease or ≥2 sites of extranodal disease. Actual administration of prophylactic intrathecal chemotherapy was at the treating physician's discretion."''
+
====CNS prophylaxis==== ''"recommended in patients with paraspinal disease, paranasal sinus disease, testicular disease, bone marrow disease, diffuse osseous disease or ≥2 sites of extranodal disease. Actual administration of prophylactic intrathecal chemotherapy was at the treating physician's discretion."''
  
 
===References===
 
===References===
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|-
 
|-
 
|}
 
|}
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Epirubicin (Ellence)]] 50 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Vinblastine (Velban)]] 5 mg/m2 IV once on day 1
+
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Prednisone (Sterapred)]] 50 mg/m2 PO/IV once per day on days 1 to 5
+
*[[Vinblastine (Velban)]] 5 mg/m<sup>2</sup> IV once on day 1
 +
*[[Prednisone (Sterapred)]] 50 mg/m<sup>2</sup> PO/IV once per day on days 1 to 5
  
−
Supportive medications:
+
====Supportive medications====
 
*Prophylactic [[Filgrastim (Neupogen)|G-CSF]] used for persisting grade 4 neutropenia or febrile neutropenia.
 
*Prophylactic [[Filgrastim (Neupogen)|G-CSF]] used for persisting grade 4 neutropenia or febrile neutropenia.
 
*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] (dose/route/schedule not specified) prophylaxis.
 
*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] (dose/route/schedule not specified) prophylaxis.
 
*Erythropoietin use was allowed for hemoglobin <11 g/dL.
 
*Erythropoietin use was allowed for hemoglobin <11 g/dL.
  
−
'''21-day cycles x 6 cycles'''
+
'''21-day cycle for 6 cycles'''
  
 
====Radiation therapy====
 
====Radiation therapy====
Line 1,423: Line 1,428:
  
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
  
−
'''21-day cycle x 3 cycles, followed by:'''
+
'''21-day cycle for 3 cycles, followed by:'''
  
 
====Radiation therapy====
 
====Radiation therapy====
Line 1,436: Line 1,441:
  
 
====Consolidation radioimmunotherapy====
 
====Consolidation radioimmunotherapy====
−
*[[Rituximab (Rituxan)]] 250 mg/m2 IV once on day 1, then another single dose on day 7, 8 or 9
+
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once on day 1, then another single dose on day 7, 8 or 9
 
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 0.4 mCi/kg (maximum dose of 32 mCi) IV once, given within four hours of second dose of [[Rituximab (Rituxan)]]
 
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 0.4 mCi/kg (maximum dose of 32 mCi) IV once, given within four hours of second dose of [[Rituximab (Rituxan)]]
  
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|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per cycle or day 1 before the start of EPOCH (depending on reference)
 +
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 4 (total dose of 200 mg/m2)
 +
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO BID on days 1 to 5
 +
*[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 4 (total dose of 1.6 mg/m2)
 +
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once over 15 minutes on day 5
 +
*[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 4 (total dose of 40 mg/m2)
  
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per cycle or day 1 before the start of EPOCH (depending on reference)
+
====Supportive medications====
−
*[[Etoposide (Vepesid)]] 50 mg/m2/day IV continuous infusion on days 1 to 4 (total dose of 200 mg/m2)
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO BID on days 1 to 5
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/m2/day IV continuous infusion on days 1 to 4 (total dose of 1.6 mg/m2)
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once over 15 minutes on day 5
 
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m2/day IV continuous infusion on days 1 to 4 (total dose of 40 mg/m2)
 
−
 
 
−
Supportive medications:
 
 
*Growth factor support with one of the following:
 
*Growth factor support with one of the following:
 
**[[Filgrastim (Neupogen)]] 5 mcg/kg SQ once per day, starting on day 6 and continuing until ANC >5,000/uL past nadir
 
**[[Filgrastim (Neupogen)]] 5 mcg/kg SQ once per day, starting on day 6 and continuing until ANC >5,000/uL past nadir
Line 1,510: Line 1,515:
 
*Only in García-Suárez et al. 2007: [[Darbepoetin alfa (Aranesp)]] 2.25 ug/kg SC when hemoglobin concentration was ≤100 g/l.
 
*Only in García-Suárez et al. 2007: [[Darbepoetin alfa (Aranesp)]] 2.25 ug/kg SC when hemoglobin concentration was ≤100 g/l.
  
−
'''21-day cycle x 6 to 8 cycles'''
+
'''21-day cycle for 6 to 8 cycles'''
  
−
Dose-adjustments for EPOCH protocol:
+
====Dose modifications====
 
*Start cycle 1 as described above.
 
*Start cycle 1 as described above.
 
*Obtain CBCs twice per week for nadir measurements.
 
*Obtain CBCs twice per week for nadir measurements.
Line 1,567: Line 1,572:
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
|-
 
|-
−
|[http://www.sciencedirect.com/science/article/pii/S215226501400411X Oki et al. 2014]
+
|[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00411-X/fulltext Oki et al. 2014]
 
|<span  
 
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
Line 1,576: Line 1,581:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Doxorubicin liposomal (Doxil)]] 40 mg/m2 (maximum dose of 90 mg) IV over 60 minutes once on day 1
+
*[[Doxorubicin liposomal (Doxil)]] 40 mg/m<sup>2</sup> (maximum dose of 90 mg) IV over 60 minutes once on day 1
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg per IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg per IV once on day 1
−
*[[Prednisone (Sterapred)]] 40 mg/m2 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
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Filgrastim (Neupogen)]] 5 μg/kg SC once per day from day 2 until ANC > 3000/μl
 
*[[Filgrastim (Neupogen)]] 5 μg/kg SC once per day from day 2 until ANC > 3000/μl
 
OR
 
OR
 
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2
 
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2
  
−
Dose modifications:
+
====Dose modifications====
 
*Dose reduction level 1 (see paper for triggers):
 
*Dose reduction level 1 (see paper for triggers):
 
**[[Doxorubicin liposomal (Doxil)]] reduced to 35 mg/m2
 
**[[Doxorubicin liposomal (Doxil)]] reduced to 35 mg/m2
Line 1,596: Line 1,601:
 
**[[Cyclophosphamide (Cytoxan)]] reduced to 450 mg/m2
 
**[[Cyclophosphamide (Cytoxan)]] reduced to 450 mg/m2
  
−
'''21-day cycle x 6 to 8 cycles'''
+
'''21-day cycle for 6 to 8 cycles'''
  
 
===Regimen #2 {{#subobject:5fd9ca|Variant=1}}===
 
===Regimen #2 {{#subobject:5fd9ca|Variant=1}}===
Line 1,614: Line 1,619:
  
 
''Only the dose of liposomal doxorubicin and number of cycles used was specified in the abstract.  The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.''  
 
''Only the dose of liposomal doxorubicin and number of cycles used was specified in the abstract.  The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.''  
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin liposomal (Doxil)]] 30 mg/m2 IV once on day 1
+
*[[Doxorubicin liposomal (Doxil)]] 30 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
  
−
'''21-day cycle x 6 cycles'''
+
'''21-day cycle for 6 cycles'''
  
 
===References===
 
===References===
 
# Zaja F, Tomadini V, Zaccaria A, Lenoci M, Battista M, Molinari AL, Fabbri A, Battista R, Cabras MG, Gallamini A, Fanin R. CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2006 Oct;47(10):2174-80. [http://informahealthcare.com/doi/full/10.1080/10428190600799946 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/17071492 PubMed]
 
# Zaja F, Tomadini V, Zaccaria A, Lenoci M, Battista M, Molinari AL, Fabbri A, Battista R, Cabras MG, Gallamini A, Fanin R. CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2006 Oct;47(10):2174-80. [http://informahealthcare.com/doi/full/10.1080/10428190600799946 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/17071492 PubMed]
−
# Oki Y, Ewer MS, Lenihan DJ, Fisch MJ, Hagemeister FB, Fanale M, Romaguera J, Pro B, Fowler N, Younes A, Astrow AB, Huang X, Kwak LW, Samaniego F, McLaughlin P, Neelapu SS, Wang M, Fayad LE, Durand JB, Rodriguez MA. Pegylated liposomal doxorubicin replacing conventional doxorubicin in standard R-CHOP chemotherapy for elderly patients with diffuse large B-cell lymphoma: an open label, single arm, phase II trial. Clin Lymphoma Myeloma Leuk. 2015 Mar;15(3):152-8. Epub 2014 Sep 28. [http://www.sciencedirect.com/science/article/pii/S215226501400411X link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25445468 PubMed]
+
# Oki Y, Ewer MS, Lenihan DJ, Fisch MJ, Hagemeister FB, Fanale M, Romaguera J, Pro B, Fowler N, Younes A, Astrow AB, Huang X, Kwak LW, Samaniego F, McLaughlin P, Neelapu SS, Wang M, Fayad LE, Durand JB, Rodriguez MA. Pegylated liposomal doxorubicin replacing conventional doxorubicin in standard R-CHOP chemotherapy for elderly patients with diffuse large B-cell lymphoma: an open label, single arm, phase II trial. Clin Lymphoma Myeloma Leuk. 2015 Mar;15(3):152-8. Epub 2014 Sep 28. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00411-X/fulltext link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344896/ link to PMC article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25445468 PubMed]
  
 
==R-CEOP90 (Epirubicin) {{#subobject:ebcd7e|Regimen=1}}==
 
==R-CEOP90 (Epirubicin) {{#subobject:ebcd7e|Regimen=1}}==
Line 1,632: Line 1,637:
 
|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
R-CEOP90: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin ('''<u>90</u>''' mg/m2 dosing), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
+
R-CEOP90: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin ('''<u>90</u>''' mg/m<sup>2</sup> dosing), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
  
 
===Regimen {{#subobject:d0b303|Variant=1}}===
 
===Regimen {{#subobject:d0b303|Variant=1}}===
Line 1,650: Line 1,655:
  
 
''This regimen is intended to reduce cardiotoxicity and was not just for patients with contraindicated doxorubicin. Note that the cycle length is not explicitly defined in the paper but was reported as a median of 21 days (range 21 to 33 days).''  
 
''This regimen is intended to reduce cardiotoxicity and was not just for patients with contraindicated doxorubicin. Note that the cycle length is not explicitly defined in the paper but was reported as a median of 21 days (range 21 to 33 days).''  
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 2
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 2
−
*[[Epirubicin (Ellence)]] 90 mg/m2 IV once on day 2
+
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 2
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 2
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 2
 
*[[Prednisolone (Millipred)]] 100 mg/day on days 2 to 6
 
*[[Prednisolone (Millipred)]] 100 mg/day on days 2 to 6
  
−
'''21-day cycle x 4 cycles followed by involved field radiotherapy (30-45 Gy) of bulky disease and extranodal and residual masses for patients with stage IA or IIA disease; 6 cycles for all others'''
+
'''21-day cycle for 4 cycles followed by involved field radiotherapy (30-45 Gy) of bulky disease and extranodal and residual masses for patients with stage IA or IIA disease; 6 cycles for all others'''
  
 
===References===
 
===References===
Line 1,685: Line 1,690:
  
 
''This regimen is intended for patients with a contraindication to anthracyclines. Only the dose of etoposide and number of cycles used was specified in the abstract.  The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.''  
 
''This regimen is intended for patients with a contraindication to anthracyclines. Only the dose of etoposide and number of cycles used was specified in the abstract.  The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.''  
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Etoposide (Vepesid)]] 50 mg/m2 IV once on day 1; 100 mg/m2 PO once per day on days 2 & 3
+
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV once on day 1; 100 mg/m<sup>2</sup> PO once per day on days 2 & 3
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
−
**Alternate dosing used in the R-CHOP regimens described in Coiffier et al. 2002 & 2010; Feugier et al. 2005; Mounier et al. 2012 - LNH-98.5 is [[Prednisone (Sterapred)]] 40 mg/m2 PO once per day on days 1 to 5
+
**Alternate dosing used in the R-CHOP regimens described in Coiffier et al. 2002 & 2010; Feugier et al. 2005; Mounier et al. 2012 - LNH-98.5 is [[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
'''21-day cycles x 3 to 4 cycles +/- radiation therapy for patients with limited stage disease; 6 cycles for patients with advanced stage disease'''
+
'''21-day cycle for 3 to 4 cycles +/- radiation therapy for patients with limited stage disease; 6 cycles for patients with advanced stage disease'''
  
 
===References===
 
===References===
Line 1,719: Line 1,724:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin liposomal (Doxil)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin liposomal (Doxil)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine liposomal (Marqibo)]] 2 mg/m2 IV once on day 1
+
*[[Vincristine liposomal (Marqibo)]] 2 mg/m<sup>2</sup> IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
  
−
'''21-day cycles x 6 cycles; stage I patients with no LN > 5 cm received 3 cycles followed by local XRT'''
+
'''21-day cycle for 6 cycles; stage I patients with no LN > 5 cm received 3 cycles followed by local XRT'''
  
 
===References===
 
===References===
Line 1,756: Line 1,761:
  
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
−
*[[Prednisone (Sterapred)]] 100 mg/m2 PO once per day on days 1 to 5
+
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
'''21-day cycle x 4 to 6 cycles, followed in 3 to 12 weeks by:'''
+
'''21-day cycle for 4 to 6 cycles, followed in 3 to 12 weeks by:'''
  
 
====Consolidation radioimmunotherapy====
 
====Consolidation radioimmunotherapy====
−
*[[Rituximab (Rituxan)]] 250 mg/m2 IV once per day on days 1 & 8
+
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 14.8 MBq/kg IV once on day 8
 
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 14.8 MBq/kg IV once on day 8
  
Line 1,796: Line 1,801:
  
 
''Intended for use in patients unlikely to tolerate anthracyclines due to cardiac comorbidity.''
 
''Intended for use in patients unlikely to tolerate anthracyclines due to cardiac comorbidity.''
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
*[[Gemcitabine (Gemzar)]] as follows:
 
*[[Gemcitabine (Gemzar)]] as follows:
−
**Cycle 1: 750 mg/m2 IV over 30 minutes once per day on days 1 & 8  
+
**Cycle 1: 750 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8  
−
**Cycle 2: 875 mg/m2 IV over 30 minutes once per day on days 1 & 8
+
**Cycle 2: 875 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
−
**Cycles 3 to 6: 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
+
**Cycles 3 to 6: 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
*[[Prednisolone (Millipred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisolone (Millipred)]] 100 mg PO once per day on days 1 to 5
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Acetaminophen (Tylenol)]] 1000 mg (route not specified) prior to [[Rituximab (Rituxan)]]
 
*[[Acetaminophen (Tylenol)]] 1000 mg (route not specified) prior to [[Rituximab (Rituxan)]]
 
*[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg IV prior to [[Rituximab (Rituxan)]]
 
*[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg IV prior to [[Rituximab (Rituxan)]]
 
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 9
 
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 9
  
−
CNS prophylaxis:
+
====CNS prophylaxis====
 
*[[Methotrexate (MTX)]] 12.5 mg IT x 3 cycles (timing not specified) for patients at high risk of CNS relapse
 
*[[Methotrexate (MTX)]] 12.5 mg IT x 3 cycles (timing not specified) for patients at high risk of CNS relapse
  
−
'''21-day cycle x 6 cycles'''
+
'''21-day cycle for 6 cycles'''
  
 
===References===
 
===References===
Line 1,841: Line 1,846:
 
|-
 
|-
 
|}
 
|}
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 1500 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 65 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 65 mg/m<sup>2</sup> IV once on day 1
−
*[[Prednisone (Sterapred)]] 60 mg/m2 once per day on days 1 to 5
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
 +
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> once per day on days 1 to 5
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Pegfilgrastim (Neulasta)]] given after each cycle
 
*[[Pegfilgrastim (Neulasta)]] given after each cycle
  
−
'''21-day cycle x 3 cycles'''
+
'''21-day cycle for 3 cycles'''
  
 
''Patients with a negative PET-CT after 3 cycles received another 3 cycles of R-MegaCHOP for a total of 6 cycles; others underwent intensification of treatment with [[Diffuse_large_B-cell_lymphoma#R-IFE|R-IFE]].''
 
''Patients with a negative PET-CT after 3 cycles received another 3 cycles of R-MegaCHOP for a total of 6 cycles; others underwent intensification of treatment with [[Diffuse_large_B-cell_lymphoma#R-IFE|R-IFE]].''
Line 1,878: Line 1,884:
 
|-
 
|-
 
|}
 
|}
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once on day 1
 +
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once on day 1
 
*[[Vincristine (Oncovin)]] 1 mg IV once on day 1
 
*[[Vincristine (Oncovin)]] 1 mg IV once on day 1
−
*[[Prednisone (Sterapred)]] 40 mg/m2 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
 
**No dose adjustments for hematologic toxicity.  If needed, the subsequent R-miniCHOP cycle was postponed until neutrophil count was = 1.0 x 10<sup>9</sup>/L and platelet count was = 100 x 10<sup>9</sup>/L, with a maximum of 28 days between cycles.  Treatment was stopped if patients' counts were not adequate within 28 days.  
 
**No dose adjustments for hematologic toxicity.  If needed, the subsequent R-miniCHOP cycle was postponed until neutrophil count was = 1.0 x 10<sup>9</sup>/L and platelet count was = 100 x 10<sup>9</sup>/L, with a maximum of 28 days between cycles.  Treatment was stopped if patients' counts were not adequate within 28 days.  
  
−
Supportive medications:
+
====Supportive medications====
 
*"Prevention of tumour lysis syndrome by alkalinisation or hypouricaemic drugs was done if necessary."
 
*"Prevention of tumour lysis syndrome by alkalinisation or hypouricaemic drugs was done if necessary."
 
*[[Antiemesis | Serotonin (5-HT3) antagonist]] given every cycle.
 
*[[Antiemesis | Serotonin (5-HT3) antagonist]] given every cycle.
Line 1,891: Line 1,898:
 
**Patients with severe neutropenia or neutropenic fever received [[Filgrastim (Neupogen) | G-CSF]] (dose not specified) SQ on days 6 to 13 of the subsequent cycle until neutrophils were = 1.0 x 10<sup>9</sup>/L.
 
**Patients with severe neutropenia or neutropenic fever received [[Filgrastim (Neupogen) | G-CSF]] (dose not specified) SQ on days 6 to 13 of the subsequent cycle until neutrophils were = 1.0 x 10<sup>9</sup>/L.
  
−
'''21-day cycles x 6 cycles'''
+
'''21-day cycle for 6 cycles'''
  
 
===References===
 
===References===
Line 1,919: Line 1,926:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 14
 
*[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 14
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
−
*[[Prednisone (Sterapred)]] 40 mg/m2 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
  
−
CNS prophylaxis for "at risk" patients:
+
===CNS prophylaxis===
 +
*For "at risk" patients:
 
*[[Methotrexate (MTX)]] 12 mg IT once on day 1 of first 4 cycles
 
*[[Methotrexate (MTX)]] 12 mg IT once on day 1 of first 4 cycles
  
−
Supportive medications:
+
====Supportive medications====
 
*[[:Category:Granulocyte_growth_factors|Granulocyte colony-stimulating factors]] (dose/duration not specified)
 
*[[:Category:Granulocyte_growth_factors|Granulocyte colony-stimulating factors]] (dose/duration not specified)
 
*[[:Category:Low_molecular_weight_heparins|Low-molecular-weight heparins]] (dose/duration not specified)
 
*[[:Category:Low_molecular_weight_heparins|Low-molecular-weight heparins]] (dose/duration not specified)
Line 1,936: Line 1,944:
 
*[[Lamivudine (Epivir)]] (dose/duration not specified) for carriers of hepatitis B virus  
 
*[[Lamivudine (Epivir)]] (dose/duration not specified) for carriers of hepatitis B virus  
  
−
'''21-day cycles x 6 cycles'''
+
'''21-day cycle for 6 cycles'''
  
 
===Regimen #2 {{#subobject:ea91fc|Variant=1}}===
 
===Regimen #2 {{#subobject:ea91fc|Variant=1}}===
Line 1,952: Line 1,960:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 10
 
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 10
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
−
*[[Prednisone (Sterapred)]] 100 mg/m2 PO once per day on days 1 to 5
+
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2
 
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2
 
*[[Aspirin]] 81 mg PO once per day unless on therapeutic dose [[Warfarin (Coumadin)]] or [[:Category:Low_molecular_weight_heparins|low molecular weight heparin]]
 
*[[Aspirin]] 81 mg PO once per day unless on therapeutic dose [[Warfarin (Coumadin)]] or [[:Category:Low_molecular_weight_heparins|low molecular weight heparin]]
  
−
'''21-day cycles x up to 6 cycles'''
+
'''21-day cycle for up to 6 cycles'''
  
 
===Regimen #3 {{#subobject:9ec4c2|Variant=1}}===
 
===Regimen #3 {{#subobject:9ec4c2|Variant=1}}===
Line 1,980: Line 1,988:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
*[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 14
 
*[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 14
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
−
*[[Prednisone (Sterapred)]] 40 mg/m2 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
  
−
Supportive medications:
+
====Supportive medications====
 
*[[:Category:Granulocyte_growth_factors|Granulocyte colony-stimulating factors]] (dose/duration not specified)
 
*[[:Category:Granulocyte_growth_factors|Granulocyte colony-stimulating factors]] (dose/duration not specified)
 
*[[:Category:Low_molecular_weight_heparins|Low-molecular-weight heparins]] (dose/duration not specified)
 
*[[:Category:Low_molecular_weight_heparins|Low-molecular-weight heparins]] (dose/duration not specified)
Line 1,994: Line 2,002:
 
*[[Lamivudine (Epivir)]] for occult hepatitis B carriers
 
*[[Lamivudine (Epivir)]] for occult hepatitis B carriers
  
−
'''21-day cycles x 6 cycles'''
+
'''21-day cycle for 6 cycles'''
  
 
===References===
 
===References===
Line 2,028: Line 2,036:
  
 
''Doses here are the phase II dose of bortezomib and the R-CHOP protocol as specified in the phase I report by Furman et al. 2010''
 
''Doses here are the phase II dose of bortezomib and the R-CHOP protocol as specified in the phase I report by Furman et al. 2010''
−
 
+
====Chemotherapy====
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 (route not specified) once per day on days 1 & 4 (day 1 administered '''prior to R-CHOP''')
+
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> (route not specified) once per day on days 1 & 4 (day 1 administered '''prior to R-CHOP''')
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
  
−
Supportive medications:
+
====Supportive medications====
 
*"Standard" [[Acetaminophen (Tylenol)]] and [[Diphenhydramine (Benadryl)]] prior to [[Rituximab (Rituxan)]]
 
*"Standard" [[Acetaminophen (Tylenol)]] and [[Diphenhydramine (Benadryl)]] prior to [[Rituximab (Rituxan)]]
  
−
'''21-day cycle x 6 cycles'''
+
'''21-day cycle for 6 cycles'''
  
 
===References===
 
===References===
Line 2,076: Line 2,084:
  
 
''Treatment preceded by [[#REI|REI consolidation]] x 4.''
 
''Treatment preceded by [[#REI|REI consolidation]] x 4.''
 +
====Chemotherapy====
 +
*[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup> SC once per day on days 1 to 4
  
−
*[[Cytarabine (Cytosar)]] 100 mg/m2 SC once per day on days 1 to 4
+
'''14-day cycle for 2 cycles'''
−
 
 
−
'''14-day cycle x 2 cycles'''
 
  
 
===References===
 
===References===
Line 2,115: Line 2,123:
  
 
''Treatment preceded by [[#ACVBP-R|ACVBP-R]] x 4.''
 
''Treatment preceded by [[#ACVBP-R|ACVBP-R]] x 4.''
 +
====Chemotherapy====
 +
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once on day 1
  
−
*[[Methotrexate (MTX)]] 3000 mg/m2 IV once on day 1
+
====Supportive medications====
−
 
 
−
Supportive medications:
 
 
*[[Folinic acid (Leucovorin)|Calcium folinate - Folinic acid (Leucovorin)]] rescue
 
*[[Folinic acid (Leucovorin)|Calcium folinate - Folinic acid (Leucovorin)]] rescue
  
−
'''14-day cycle x 2 cycles'''
+
'''14-day cycle for 2 cycles'''
  
 
''Treatment followed in 2 weeks by [[#REI|REI consolidation]].''
 
''Treatment followed in 2 weeks by [[#REI|REI consolidation]].''
Line 2,214: Line 2,222:
  
 
''Treatment preceded by [[#Methotrexate_.28MTX.29|methotrexate consolidation]] x 2.''
 
''Treatment preceded by [[#Methotrexate_.28MTX.29|methotrexate consolidation]] x 2.''
 +
====Chemotherapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 +
*[[Etoposide (Vepesid)]] 300 mg/m<sup>2</sup> IV once on day 1
 +
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once on day 1
  
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
'''14-day cycle for 4 cycles'''
−
*[[Etoposide (Vepesid)]] 300 mg/m2 IV once on day 1
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m2 IV once on day 1
 
−
 
 
−
'''14-day cycle x 4 cycles'''
 
  
 
''Treatment followed in 2 weeks by [[#Cytarabine_.28Cytosar.29|cytarabine consolidation]].''
 
''Treatment followed in 2 weeks by [[#Cytarabine_.28Cytosar.29|cytarabine consolidation]].''
Line 2,258: Line 2,266:
  
 
''Treatment preceded by 8 infusions of rituximab (375 mg/m2) and 4 to 8 cycles of CHOP-like chemotherapy. Patients required to be in CR or CRu prior to enrollment. The protocol was amended after the first 69 patients enrolled to increase length of treatment from 1 to 2 years.''
 
''Treatment preceded by 8 infusions of rituximab (375 mg/m2) and 4 to 8 cycles of CHOP-like chemotherapy. Patients required to be in CR or CRu prior to enrollment. The protocol was amended after the first 69 patients enrolled to increase length of treatment from 1 to 2 years.''
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once every 2 months
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once every 2 months
  
 
'''1 to 2 year course'''
 
'''1 to 2 year course'''
Line 2,288: Line 2,296:
  
 
''Preceded by "standard treatment" which was not further described in the paper, beyond that a majority of patient received R-CHOP (see Tables).''
 
''Preceded by "standard treatment" which was not further described in the paper, beyond that a majority of patient received R-CHOP (see Tables).''
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once every 3 months
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once every 3 months
  
 
'''2 year course'''
 
'''2 year course'''
Line 2,334: Line 2,342:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Dexamethasone (Decadron)]] 40 mg IV over 15 minutes once per day on days 1 to 4
 
*[[Dexamethasone (Decadron)]] 40 mg IV over 15 minutes once per day on days 1 to 4
−
*[[Cytarabine (Cytosar)]]  
+
*[[Cytarabine (Cytosar)]] as follows:
−
**2000 mg/m2 IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses) in patients younger than 70
+
**Patients younger than 70: 2000 mg/m<sup>2</sup> IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
−
**1000 mg/m2 IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses) in patients older than 70
+
**Patients older than 70: 1000 mg/m<sup>2</sup> IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
−
*[[Cisplatin (Platinol)]] 100 mg/m2 IV continuous infusion over 24 hours on day 1
+
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 1
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Metoclopramide (Reglan)]] 1 mg/kg (route and frequency not indicated)
 
*[[Metoclopramide (Reglan)]] 1 mg/kg (route and frequency not indicated)
 
*[[Diphenhydramine (Benadryl)]] 25 mg IV (frequency not indicated)
 
*[[Diphenhydramine (Benadryl)]] 25 mg IV (frequency not indicated)
Line 2,398: Line 2,406:
 
|-
 
|-
 
|}
 
|}
−
*[[Etoposide (Vepesid)]] 40 mg/m2 IV over 1 hour once per day on days 1 to 4
+
====Chemotherapy====
 +
*[[Etoposide (Vepesid)]] 40 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 4
 
*[[Methylprednisolone (Solumedrol)]] 250-500 mg IV over 15 minutes once per day on days 1 to 5
 
*[[Methylprednisolone (Solumedrol)]] 250-500 mg IV over 15 minutes once per day on days 1 to 5
−
*[[Cytarabine (Cytosar)]] 2000 mg/m2 IV over 2 hours once on day 5
+
*[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV over 2 hours once on day 5
−
*[[Cisplatin (Platinol)]] 25 mg/m2/day IV continuous infusion on days 1 to 4 (total dose per cycle: 100 mg/m2)  
+
*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 4 (total dose per cycle: 100 mg/m2)  
  
−
Supportive medications:
+
====Supportive medications====
 
*At least 1 liter normal saline with 25 to 50 g [[Mannitol]] once per day throughout chemotherapy
 
*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 "given regularly"
 
*[[Metoclopramide (Reglan)]] 0.5 to 1 mg/kg "given regularly"
Line 2,443: Line 2,452:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Gemcitabine (Gemzar)]] as follows:
 
*[[Gemcitabine (Gemzar)]] as follows:
−
**Cycle 1: 1250 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
+
**Cycle 1: 1250 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
−
**Subsequent cycles (if no hematologic or nonhematologic toxicities): Optional increase to 1500 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
+
**Subsequent cycles (if no hematologic or nonhematologic toxicities): Optional increase to 1500 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
  
 
'''4-week cycles until progression or intolerance'''
 
'''4-week cycles until progression or intolerance'''
Line 2,486: Line 2,495:
  
 
''Dose & schedule is as given in Pettengell et al. CALGB 8552 used a different dose & schedule.''
 
''Dose & schedule is as given in Pettengell et al. CALGB 8552 used a different dose & schedule.''
 +
====Chemotherapy====
 +
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 2
  
−
*[[Ifosfamide (Ifex)]] 3000 mg/m2 IV once per day on days 1 & 2
+
====Supportive medications====
−
 
 
−
Supportive medications:
 
 
*[[Mesna (Mesnex)]] dose not specified
 
*[[Mesna (Mesnex)]] dose not specified
  
Line 2,540: Line 2,549:
 
|}
 
|}
  
−
''Germann et al. give a range of 100 to 130 mg/m2; Oki et al. used the 130 mg/m2 dosage; Pettengell et al. used the 100 mg/m2 dosage.''
+
''Germann et al. give a range of 100 to 130 mg/m2; Oki et al. used the 130 mg/m<sup>2</sup> dosage; Pettengell et al. used the 100 mg/m<sup>2</sup> dosage.''
−
 
+
====Chemotherapy====
−
*[[Oxaliplatin (Eloxatin)]] 100 to 130 mg/m2 IV once on day 1
+
*[[Oxaliplatin (Eloxatin)]] 100 to 130 mg/m<sup>2</sup> IV once on day 1
  
 
'''21-day cycles'''
 
'''21-day cycles'''
Line 2,550: Line 2,559:
 
# '''Review:''' Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82. Review. [http://informahealthcare.com/doi/abs/10.1080/10428190290021632 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12148908 PubMed]
 
# '''Review:''' Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82. Review. [http://informahealthcare.com/doi/abs/10.1080/10428190290021632 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12148908 PubMed]
 
# Oki Y, McLaughlin P, Pro B, Hagemeister FB, Bleyer A, Loyer E, Younes A. Phase II study of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma. Cancer. 2005 Aug 15;104(4):781-7. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.21219/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15973667 PubMed]
 
# Oki Y, McLaughlin P, Pro B, Hagemeister FB, Bleyer A, Loyer E, Younes A. Phase II study of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma. Cancer. 2005 Aug 15;104(4):781-7. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.21219/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15973667 PubMed]
−
# Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [http://www.sciencedirect.com/science/article/pii/S1470204512702127 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+
# Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
  
 
==Pixantrone (Pixuvri) {{#subobject:bedd78|Regimen=1}}==
 
==Pixantrone (Pixuvri) {{#subobject:bedd78|Regimen=1}}==
Line 2,580: Line 2,589:
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Pixantrone (Pixuvri)]] 85 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
  
−
*[[Pixantrone (Pixuvri)]] 85 mg/m2 IV once per day on days 1, 8, 15
+
'''28-day cycle for up to 6 cycles'''
−
 
 
−
'''28-day cycle x up to 6 cycles'''
 
  
 
===References===
 
===References===
Line 2,618: Line 2,627:
 
|-
 
|-
 
|}
 
|}
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
====Chemotherapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
−
*[[Cytarabine (Cytosar)]] 2000 mg/m2 IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
+
*[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
−
*[[Cisplatin (Platinol)]] 100 mg/m2 IV continuous infusion over 24 hours on day 1
+
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 1
  
−
'''21-day cycles x up to 3 cycles'''
+
'''21-day cycle for up to 3 cycles'''
  
 
''Responders proceeded to stem-cell mobilization and [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|autologous stem cell transplant]].''
 
''Responders proceeded to stem-cell mobilization and [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|autologous stem cell transplant]].''
Line 2,652: Line 2,662:
  
 
''Note: the paper makes reference to Velasquez et al. 1988 to describe this regimen, although this reference is for DHAP, not R-DHAP. The paper also contains the following regimen information:''
 
''Note: the paper makes reference to Velasquez et al. 1988 to describe this regimen, although this reference is for DHAP, not R-DHAP. The paper also contains the following regimen information:''
−
 
+
====Chemotherapy====
 
*[[Rituximab (Rituxan)]] as follows (given first before other chemotherapy):
 
*[[Rituximab (Rituxan)]] as follows (given first before other chemotherapy):
−
**Cycle 1: 375 mg/m2 IV once per day on days -1 & 1
+
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days -1 & 1
−
**Cycle 2: 375 mg/m2 IV once on day 1  
+
**Cycle 2: 375 mg/m<sup>2</sup> IV once on day 1  
 
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
−
*[[Cytarabine (Cytosar)]] 2000 mg/m2 IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
+
*[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
−
*[[Cisplatin (Platinol)]] 100 mg/m2 IV continuous infusion over 24 hours on day 1
+
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 1
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Filgrastim (Neupogen) | G-CSF]] "depending on site policy, with R-DHAP, but always after the third cycle until the end of leukaphereses"
 
*[[Filgrastim (Neupogen) | G-CSF]] "depending on site policy, with R-DHAP, but always after the third cycle until the end of leukaphereses"
  
−
'''21-day cycles x 3 cycles'''
+
'''21-day cycle for 3 cycles'''
  
 
''Patients with complete or partial response then received [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|BEAM autologous stem-cell transplant]].''
 
''Patients with complete or partial response then received [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|BEAM autologous stem-cell transplant]].''
Line 2,715: Line 2,725:
 
|-
 
|-
 
|}
 
|}
−
 
 
''Regimen details are based on ESHAP paper from 1994.  Per retrospective review (Martin et al. 2008), 90% of patients given R-ESHAP received rituximab on day 1, 10% on day 5.''
 
''Regimen details are based on ESHAP paper from 1994.  Per retrospective review (Martin et al. 2008), 90% of patients given R-ESHAP received rituximab on day 1, 10% on day 5.''
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1 (or day 5)
+
====Chemotherapy====
−
*[[Etoposide (Vepesid)]] 40 mg/m2 IV over 1 hour once per day on days 1 to 4
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 (or day 5)
 +
*[[Etoposide (Vepesid)]] 40 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 4
 
*[[Methylprednisolone (Solumedrol)]] 250 to 500 mg IV over 15 minutes once per day on days 1 to 5
 
*[[Methylprednisolone (Solumedrol)]] 250 to 500 mg IV over 15 minutes once per day on days 1 to 5
 
**In Martín et al. 2008, methylprednisolone could either be given on days 1 to 4 or days 1 to 5, with patients receiving total doses of anywhere from 1000 mg per cycle to 2500 mg per cycle
 
**In Martín et al. 2008, methylprednisolone could either be given on days 1 to 4 or days 1 to 5, with patients receiving total doses of anywhere from 1000 mg per cycle to 2500 mg per cycle
−
*[[Cytarabine (Cytosar)]] 2000 mg/m2 IV over 2 hours once on day 5
+
*[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV over 2 hours once on day 5
−
*[[Cisplatin (Platinol)]] 25 mg/m2/day IV continuous infusion over 96 hours (total dose per cycle: 100 mg/m2) on days 1 to 4
+
*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours (total dose per cycle: 100 mg/m2) on days 1 to 4
  
−
Supportive medications:
+
====Supportive medications====
 
*At least 1 liter normal saline with 25 to 50 g [[Mannitol]] once per day throughout chemotherapy
 
*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 "given regularly"
 
*[[Metoclopramide (Reglan)]] 0.5 to 1 mg/kg "given regularly"
Line 2,765: Line 2,775:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once per day on days 1 & 8
+
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
−
*[[Cisplatin (Platinol)]] 75 mg/m2 IV once on day 1
+
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
  
−
'''21-day cycle x up to 3 cycles'''
+
'''21-day cycle for up to 3 cycles'''
  
 
''Responders proceeded to stem-cell mobilization and [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|autologous stem cell transplant]].''
 
''Responders proceeded to stem-cell mobilization and [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|autologous stem cell transplant]].''
Line 2,810: Line 2,820:
  
 
''Note: the paper refers to the non-randomized [[#R-ICE_2|Kewalramani et al. 2004 regimen]], although it has slightly different day numbering. Doses are the same.''
 
''Note: the paper refers to the non-randomized [[#R-ICE_2|Kewalramani et al. 2004 regimen]], although it has slightly different day numbering. Doses are the same.''
−
 
+
====Chemotherapy====
 
*[[Rituximab (Rituxan)]] as follows (given first before other chemotherapy):
 
*[[Rituximab (Rituxan)]] as follows (given first before other chemotherapy):
−
**Cycle 1: 375 mg/m2 IV once per day on days -1 & 1
+
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days -1 & 1
−
**Cycles 2 & 3: 375 mg/m2 IV once on day 1  
+
**Cycles 2 & 3: 375 mg/m<sup>2</sup> IV once on day 1  
−
*[[Ifosfamide (Ifex)]] 5,000 mg/m2 IV continuous infusion over 24 hours on day 2
+
*[[Ifosfamide (Ifex)]] 5,000 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 2
 
*[[Carboplatin (Paraplatin)]] AUC 5 IV (maximum dose of 800 mg per cycle) on day 2
 
*[[Carboplatin (Paraplatin)]] AUC 5 IV (maximum dose of 800 mg per cycle) on day 2
−
*[[Etoposide (Vepesid)]] 100 mg/m2 IV once per day on days 1 to 3
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Mesna (Mesnex)]] given with [[Ifosfamide (Ifex)]]; dose & schedule not specified in the paper
 
*[[Mesna (Mesnex)]] given with [[Ifosfamide (Ifex)]]; dose & schedule not specified in the paper
 
*"[[Filgrastim (Neupogen) | Granulocyte colony-stimulating factor]] was administered after R-ICE"
 
*"[[Filgrastim (Neupogen) | Granulocyte colony-stimulating factor]] was administered after R-ICE"
  
−
'''21-day cycles x 3 cycles'''
+
'''21-day cycle for 3 cycles'''
  
 
''Patients with complete or partial response then received [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|BEAM autologous stem-cell transplant]].''
 
''Patients with complete or partial response then received [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|BEAM autologous stem-cell transplant]].''
Line 2,852: Line 2,862:
 
|
 
|
 
|-
 
|-
−
|[http://www.sciencedirect.com/science/article/pii/S1470204512702127 Pettengell et al. 2012]
+
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext Pettengell et al. 2012]
 
|<span  
 
|<span  
 
style="background:#eeee00;
 
style="background:#eeee00;
Line 2,862: Line 2,872:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Vinorelbine (Navelbine)]] 30 mg/m2 IV once per day on days 1, 8, 15, 22
+
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
  
 
'''28-day cycles'''
 
'''28-day cycles'''
Line 2,870: Line 2,880:
 
# Balzarotti M, Santoro A, Tondini C, Fornier M, Bonadonna G. Activity of single agent vinorelbine in pretreated non-Hodgkin's lymphoma. Ann Oncol. 1996 Nov;7(9):970-2. [http://annonc.oxfordjournals.org/content/7/9/970.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9006750 PubMed]
 
# Balzarotti M, Santoro A, Tondini C, Fornier M, Bonadonna G. Activity of single agent vinorelbine in pretreated non-Hodgkin's lymphoma. Ann Oncol. 1996 Nov;7(9):970-2. [http://annonc.oxfordjournals.org/content/7/9/970.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9006750 PubMed]
 
# '''Review:''' Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82. Review. [http://informahealthcare.com/doi/abs/10.1080/10428190290021632 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12148908 PubMed]
 
# '''Review:''' Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82. Review. [http://informahealthcare.com/doi/abs/10.1080/10428190290021632 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12148908 PubMed]
−
# Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [http://www.sciencedirect.com/science/article/pii/S1470204512702127 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+
# Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
  
 
=Relapsed/refractory, non-randomized or retrospective data=
 
=Relapsed/refractory, non-randomized or retrospective data=
Line 2,896: Line 2,906:
  
 
''Two dosing schemas were evaluated; this is the preferred dosing regimen, per the authors.''
 
''Two dosing schemas were evaluated; this is the preferred dosing regimen, per the authors.''
−
 
+
====Chemotherapy====
 
*[[Blinatumomab (Blincyto)]] as follows:
 
*[[Blinatumomab (Blincyto)]] as follows:
 
**9 µg/day IV continuous infusion during week 1, then
 
**9 µg/day IV continuous infusion during week 1, then
Line 2,902: Line 2,912:
 
**112 µg/day IV continuous infusion for remainder of the 8-week course
 
**112 µg/day IV continuous infusion for remainder of the 8-week course
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Dexamethasone (Decadron)]] 20 mg PO 6 to 12 hours before infusion start and dose increases, 20 mg PO 1 hour before infusion start and dose increases,  and 8 mg PO TID for 2 days following infusion start and dose increases
 
*[[Dexamethasone (Decadron)]] 20 mg PO 6 to 12 hours before infusion start and dose increases, 20 mg PO 1 hour before infusion start and dose increases,  and 8 mg PO TID for 2 days following infusion start and dose increases
 
**Patients with neurologic symptoms or cytokine release syndrome received 8 mg PO/IV Q8H for up to 3 days, with a subsequent taper over 4 days
 
**Patients with neurologic symptoms or cytokine release syndrome received 8 mg PO/IV Q8H for up to 3 days, with a subsequent taper over 4 days
Line 2,947: Line 2,957:
 
====Chemotherapy====
 
====Chemotherapy====
 
''Note: the bendamustine infusion instructions are for the Treanda formulation, which was discontinued on 3/31/2016.''
 
''Note: the bendamustine infusion instructions are for the Treanda formulation, which was discontinued on 3/31/2016.''
−
*[[Bendamustine]] 120 mg/m2 IV over 60 minutes once per day on days 1 & 2 OR on days 2 & 3
+
*[[Bendamustine]] 120 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 2 OR on days 2 & 3
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
  
 
====Supportive medications====
 
====Supportive medications====
 
*"Opportunistic infection prophylaxis with [[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] and [[Acyclovir (Zovirax)]] was recommended."
 
*"Opportunistic infection prophylaxis with [[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] and [[Acyclovir (Zovirax)]] was recommended."
  
−
'''21-day cycle x up to 6 cycles'''
+
'''21-day cycle for up to 6 cycles'''
  
 
===References===
 
===References===
Line 2,989: Line 2,999:
 
|}
 
|}
 
''Bartlett et al. treated patients with undetectable CD30 by visual assessment using routine IHC. Jacobsen et al. treated patients with CD30+ non-Hodgkin lymphoma, as determined by IHC.''
 
''Bartlett et al. treated patients with undetectable CD30 by visual assessment using routine IHC. Jacobsen et al. treated patients with CD30+ non-Hodgkin lymphoma, as determined by IHC.''
−
   
+
  ====Chemotherapy====
 
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg IV over 30 minutes on day 1
 
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg IV over 30 minutes on day 1
  
Line 3,006: Line 3,016:
 
EPOCH: '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin
 
EPOCH: '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin
  
−
Synonyms: CHEOP, DA-EPOCH
+
Synonyms: CHEOP
  
 
Structured Concept: [http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary==NCI%20Thesaurus&version==12.09d&code==C63779 C63779] (NCI-T), [http://ncim.nci.nih.gov/ncimbrowser/ConceptReport.jsp?dictionary==NCI%20MetaThesaurus&code==C1880475 C1880475] (NCI-MT/UMLS)
 
Structured Concept: [http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary==NCI%20Thesaurus&version==12.09d&code==C63779 C63779] (NCI-T), [http://ncim.nci.nih.gov/ncimbrowser/ConceptReport.jsp?dictionary==NCI%20MetaThesaurus&code==C1880475 C1880475] (NCI-MT/UMLS)
Line 3,024: Line 3,034:
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup>/day (total dose of 200 mg/m2) IV continuous infusion on days 1 to 4
 +
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO on days 1 to 6
 +
*[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day (total dose of 1.6 mg/m2) IV continuous infusion on days 1 to 4
 +
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 15 minutes on day 6
 +
*[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day (total dose of 40 mg/m2) IV continuous infusion on days 1 to 4
  
−
*[[Etoposide (Vepesid)]] 50 mg/m2/day (total dose of 200 mg/m2) IV continuous infusion on days 1 to 4
+
====Supportive medications====
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO on days 1 to 6
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/m2/day (total dose of 1.6 mg/m2) IV continuous infusion on days 1 to 4
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV over 15 minutes on day 6
 
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m2/day (total dose of 40 mg/m2) IV continuous infusion on days 1 to 4
 
−
 
 
−
Supportive medications:
 
 
*[[Filgrastim (Neupogen)]] 5 mcg/kg SQ once per day, starting on day 6 and continuing until ANC >5,000/uL past nadir
 
*[[Filgrastim (Neupogen)]] 5 mcg/kg SQ once per day, starting on day 6 and continuing until ANC >5,000/uL past nadir
 
*PCP prophylaxis with any one of the following:
 
*PCP prophylaxis with any one of the following:
Line 3,038: Line 3,048:
 
**[[Pentamidine (Nebupent)]] 300 mg nebulized every 28 days
 
**[[Pentamidine (Nebupent)]] 300 mg nebulized every 28 days
  
−
'''21-day cycles x 6 to 8 cycles'''
+
'''21-day cycle for 6 to 8 cycles'''
  
 
===References===
 
===References===
Line 3,062: Line 3,072:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Everolimus (Afinitor)]] 10 mg PO once per day on an empty stomach
 
*[[Everolimus (Afinitor)]] 10 mg PO once per day on an empty stomach
  
−
Supportive medications:
+
====Supportive medications====
 
*"Patients could receive white blood cell growth factors, if neutropenia developed at physician's discretion. Erythropoietin treatment for anemia was permitted per standard guidelines."
 
*"Patients could receive white blood cell growth factors, if neutropenia developed at physician's discretion. Erythropoietin treatment for anemia was permitted per standard guidelines."
  
Line 3,093: Line 3,103:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Everolimus (Afinitor)]] 5 mg PO once per day on days 1 to 14, increased to 10 mg PO once per day for the remainder of cycle 1 and thereafter, if tolerated
 
*[[Everolimus (Afinitor)]] 5 mg PO once per day on days 1 to 14, increased to 10 mg PO once per day for the remainder of cycle 1 and thereafter, if tolerated
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per week x 4 weeks, then once on day 1 of cycle 2 onwards
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per week x 4 weeks, then once on day 1 of cycle 2 onwards
  
−
'''28-day cycles x 6 cycles''' ''Responders had the option of continuing everolimus for another 6 months.''
+
'''28-day cycle for 6 cycles'''  
 +
''Responders had the option of continuing everolimus for another 6 months.''
  
 
===References===
 
===References===
Line 3,123: Line 3,134:
 
|-
 
|-
 
|}
 
|}
−
*[[Gemcitabine (Gemzar)]] 800 mg/m2 IV once on day 1
+
====Chemotherapy====
−
*[[Vinorelbine (Navelbine)]] 15 mg/m2 IV once on day 1
+
*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin liposomal (Doxil)]] 20 mg/m2 IV once on day 1
+
*[[Vinorelbine (Navelbine)]] 15 mg/m<sup>2</sup> IV once on day 1
 +
*[[Doxorubicin liposomal (Doxil)]] 20 mg/m<sup>2</sup> IV once on day 1
  
 
'''14-day cycles'''
 
'''14-day cycles'''
Line 3,167: Line 3,179:
  
 
''Clinically meaningful responses were observed in the ABC subtype, only. Further clinical trials are currently underway.''
 
''Clinically meaningful responses were observed in the ABC subtype, only. Further clinical trials are currently underway.''
−
 
+
====Chemotherapy====
 
*[[Ibrutinib (Imbruvica)]] 560 mg PO once per day
 
*[[Ibrutinib (Imbruvica)]] 560 mg PO once per day
  
Line 3,198: Line 3,210:
  
 
''Third cycle intended to be followed by peripheral blood stem cell collection''
 
''Third cycle intended to be followed by peripheral blood stem cell collection''
−
*[[Ifosfamide (Ifex)]] 5,000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together with mesna
+
====Chemotherapy====
 +
*[[Ifosfamide (Ifex)]] 5,000 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 2, mixed together with [[Mesna (Mesnex)]]
 
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg per cycle) IV bolus once on day 2
 
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg per cycle) IV bolus once on day 2
 
**Carboplatin AUC calculated based on a 12-hour creatinine clearance
 
**Carboplatin AUC calculated based on a 12-hour creatinine clearance
−
*[[Etoposide (Vepesid)]] 100 mg/m2 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
  
−
'''14-day cycles x 3 cycles'''
+
'''14-day cycle for 3 cycles'''
  
−
Supportive medications:
+
====Supportive medications====
−
*[[Mesna (Mesnex)]] 5,000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together with [[Ifosfamide (Ifex)]]
+
*[[Mesna (Mesnex)]] 5,000 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 2, mixed together with [[Ifosfamide (Ifex)]]
 
*[[Filgrastim (Neupogen)]] 5 µg/kg SC once per day on days 5 to 12 (10 µg/kg with cycle 3, given until collection of peripheral blood stem cells)
 
*[[Filgrastim (Neupogen)]] 5 µg/kg SC once per day on days 5 to 12 (10 µg/kg with cycle 3, given until collection of peripheral blood stem cells)
  
Line 3,242: Line 3,255:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
  
Line 3,271: Line 3,284:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per week on weeks 1 to 4 of cycle 1, only
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per week on weeks 1 to 4 of cycle 1, only
  
 
'''28-day cycles'''
 
'''28-day cycles'''
Line 3,291: Line 3,304:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1 & 21
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1 & 21
  
−
'''28-day cycle x 4 cycles'''
+
'''28-day cycle for 4 cycles'''
  
 
''Patients with a response of stable disease or better proceeded to [[#Lenalidomide_.28Revlimid.29_2|maintenance lenalidomide]].''
 
''Patients with a response of stable disease or better proceeded to [[#Lenalidomide_.28Revlimid.29_2|maintenance lenalidomide]].''
Line 3,324: Line 3,337:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Mitoxantrone (Novantrone)]] 14 mg/m2 IV over 30 minutes once on day 1
+
*[[Mitoxantrone (Novantrone)]] 14 mg/m<sup>2</sup> IV over 30 minutes once on day 1
  
 
'''3-week cycles'''
 
'''3-week cycles'''
Line 3,353: Line 3,366:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Obinutuzumab (Gazyva)]] as follows:
 
*[[Obinutuzumab (Gazyva)]] as follows:
 
**Cycle 1: 1600 mg (diluted to 10 mg/mL) IV once per day on days 1 & 8
 
**Cycle 1: 1600 mg (diluted to 10 mg/mL) IV once per day on days 1 & 8
Line 3,359: Line 3,372:
 
**Initial infusion rate is 50 mg/hour.  In the absence of infusion-related reactions (IRRs), the rate is then increased by 50 mg/hour every 30 minutes, up to a maximum of 400 mg/hour.
 
**Initial infusion rate is 50 mg/hour.  In the absence of infusion-related reactions (IRRs), the rate is then increased by 50 mg/hour every 30 minutes, up to a maximum of 400 mg/hour.
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Acetaminophen (Tylenol)]] or paracetamol 650 to 1000 mg PO once 30 minutes prior to [[Obinutuzumab (Gazyva)]]
 
*[[Acetaminophen (Tylenol)]] or paracetamol 650 to 1000 mg PO once 30 minutes prior to [[Obinutuzumab (Gazyva)]]
 
*"An antihistamine" 30 minutes prior to [[Obinutuzumab (Gazyva)]]; if there were no infusion-related reactions (IRRs) requiring medication or infusion interruption, antihistamine could be omitted for subsequent infusions
 
*"An antihistamine" 30 minutes prior to [[Obinutuzumab (Gazyva)]]; if there were no infusion-related reactions (IRRs) requiring medication or infusion interruption, antihistamine could be omitted for subsequent infusions
Line 3,366: Line 3,379:
 
*Antibiotic prophylaxis allowed
 
*Antibiotic prophylaxis allowed
  
−
'''21-day cycle x 8 cycles'''
+
'''21-day cycle for 8 cycles'''
  
 
===References===
 
===References===
Line 3,392: Line 3,405:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Ofatumumab (Arzerra)]] as follows:
 
*[[Ofatumumab (Arzerra)]] as follows:
 
**Cycle 1: 1000 mg IV once per day on days 1 & 8
 
**Cycle 1: 1000 mg IV once per day on days 1 & 8
 
**Cycles 2 & 3: 1000 mg IV once on day 1
 
**Cycles 2 & 3: 1000 mg IV once on day 1
 
*[[Dexamethasone (Decadron)]] 40 mg PO/IV once per day on days 1 to 4
 
*[[Dexamethasone (Decadron)]] 40 mg PO/IV once per day on days 1 to 4
−
*[[Cytarabine (Cytosar)]] 2000 mg/m2 IV Q12H x 2 doses on day 2 (total of 2 doses)
+
*[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV Q12H x 2 doses on day 2 (total of 2 doses)
−
*[[Cisplatin (Platinol)]] 100 mg/m2 IV continuous infusion over 24 hours on day 1
+
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 1
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Filgrastim (Neupogen) | G-CSF]] or [[Pegfilgrastim (Neulasta) | Neulasta]] was recommended (no details given).
 
*[[Filgrastim (Neupogen) | G-CSF]] or [[Pegfilgrastim (Neulasta) | Neulasta]] was recommended (no details given).
  
−
'''21-day cycle x 3 cycles'''
+
'''21-day cycle for 3 cycles'''
  
 
===References===
 
===References===
Line 3,430: Line 3,443:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Ofatumumab (Arzerra)]] as follows:
 
*[[Ofatumumab (Arzerra)]] as follows:
 
**Cycle 1: 1000 mg IV once per day on days 1 & 8
 
**Cycle 1: 1000 mg IV once per day on days 1 & 8
 
**Cycles 2 & 3: 1000 mg IV once on day 1
 
**Cycles 2 & 3: 1000 mg IV once on day 1
−
*[[Ifosfamide (Ifex)]] 5,000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together with [[Mesna (Mesnex)]]
+
*[[Ifosfamide (Ifex)]] 5,000 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 2, mixed together with [[Mesna (Mesnex)]]
 
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg) IV once on day 1 OR 2 (1 dose, total)
 
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg) IV once on day 1 OR 2 (1 dose, total)
 
**Carboplatin AUC calculated based on a 12-hour creatinine clearance
 
**Carboplatin AUC calculated based on a 12-hour creatinine clearance
−
*[[Etoposide (Vepesid)]] 100 mg/m2 IV once per day on days 1 to 3
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
  
−
Supportive medications:
+
====Supportive medications====
−
*[[Mesna (Mesnex)]] 5000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together with [[Ifosfamide (Ifex)]]
+
*[[Mesna (Mesnex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 2, mixed together with [[Ifosfamide (Ifex)]]
 
*[[Filgrastim (Neupogen) | G-CSF]] or [[Pegfilgrastim (Neulasta) | Neulasta]] was recommended (no details given).
 
*[[Filgrastim (Neupogen) | G-CSF]] or [[Pegfilgrastim (Neulasta) | Neulasta]] was recommended (no details given).
  
−
'''21-day cycle x 3 cycles'''
+
'''21-day cycle for 3 cycles'''
  
 
===References===
 
===References===
Line 3,469: Line 3,482:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Ofatumumab (Arzerra)]] 300 mg IV on cycle 1 day 1, then 1000 mg IV once per week x 7 weeks (total of 8 doses)
 
*[[Ofatumumab (Arzerra)]] 300 mg IV on cycle 1 day 1, then 1000 mg IV once per week x 7 weeks (total of 8 doses)
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Acetaminophen (Tylenol)]] 1000 mg or equivalent 30 min to 2 h prior to [[Ofatumumab (Arzerra)]]
 
*[[Acetaminophen (Tylenol)]] 1000 mg or equivalent 30 min to 2 h prior to [[Ofatumumab (Arzerra)]]
 
*[[Cetirizine (Zyrtec)]] 10 mg PO or equivalent 30 min to 2 h prior to [[Ofatumumab (Arzerra)]]
 
*[[Cetirizine (Zyrtec)]] 10 mg PO or equivalent 30 min to 2 h prior to [[Ofatumumab (Arzerra)]]
Line 3,505: Line 3,518:
  
 
''The MTD for vorinostat was 300 mg in this phase I/II trial.''
 
''The MTD for vorinostat was 300 mg in this phase I/II trial.''
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m2 IV once per day on days 1 & 8
+
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
*[[Vorinostat (Zolinza)]] 300 mg PO once per day on days 1 to 10
 
*[[Vorinostat (Zolinza)]] 300 mg PO once per day on days 1 to 10
−
*[[Etoposide (Vepesid)]] 70 mg/m2 IV once on day 1
+
*[[Etoposide (Vepesid)]] 70 mg/m<sup>2</sup> IV once on day 1
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO once per day on days 1 to 10
+
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 10
  
−
'''28-day cycle x 6 cycles'''
+
'''28-day cycle for 6 cycles'''
  
 
===References===
 
===References===
Line 3,538: Line 3,551:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
*[[Dexamethasone (Decadron)]] 24 mg PO TID on days 1 to 10
 
*[[Dexamethasone (Decadron)]] 24 mg PO TID on days 1 to 10
−
*[[Carmustine (BiCNU)]] 60 mg/m2 IV once on day 2
+
*[[Carmustine (BiCNU)]] 60 mg/m<sup>2</sup> IV once on day 2
−
*[[Etoposide (Vepesid)]] 75 mg/m2 IV once per day on days 4 to 7
+
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 4 to 7
−
*[[Cytarabine (Cytosar)]] 200 mg/m2 IV BID on days 4 to 7
+
*[[Cytarabine (Cytosar)]] 200 mg/m<sup>2</sup> IV BID on days 4 to 7
−
*[[Melphalan (Alkeran)]] 20 mg/m2 IV once on day 3
+
*[[Melphalan (Alkeran)]] 20 mg/m<sup>2</sup> IV once on day 3
  
−
'''3- to 4-week cycle x 2 cycles'''
+
'''3- to 4-week cycle for 2 cycles'''
  
 
''Patient proceed to undergo [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|high dose therapy and autologous stem cell transplant]].''
 
''Patient proceed to undergo [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|high dose therapy and autologous stem cell transplant]].''
Line 3,578: Line 3,591:
  
 
====First cycle====
 
====First cycle====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 3 to 5
 
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 3 to 5
 
*[[Cytarabine (Cytosar)]] as follows:
 
*[[Cytarabine (Cytosar)]] as follows:
−
**1000 mg/m2 IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses) if younger than 60 years old
+
**Younger than 60 years: 1000 mg/m<sup>2</sup> IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses)
−
**500 mg/m2 IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses) if older than 60 years old
+
**Older than 60 years: 500 mg/m<sup>2</sup> IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses)
−
*[[Cisplatin (Platinol)]] 25 mg/m2/day IV continuous infusion on days 3 to 5
+
*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup>/day IV continuous infusion on days 3 to 5 (total dose = 75 mg/m<sup>2</sup>)
  
 
'''3-week cycle'''
 
'''3-week cycle'''
  
 
====Subsequent cycles====
 
====Subsequent cycles====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 3 to 6
 
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 3 to 6
 
*[[Cytarabine (Cytosar)]] as follows:
 
*[[Cytarabine (Cytosar)]] as follows:
−
**2000 mg/m2 IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses) if younger than 60 years old
+
**Younger than 60 years: 2000 mg/m<sup>2</sup> IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses)  
−
**1000 mg/m2 IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses) if older than 60 years old
+
**Older than 60 years: 1000 mg/m<sup>2</sup> IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses)
−
*[[Cisplatin (Platinol)]] 25 mg/m2/day IV continuous infusion on days 3 to 6
+
*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup>/day IV continuous infusion on days 3 to 6 (total dose per cycle = 100 mg/m<sup>2</sup>)
  
 
'''3-week cycle up to 3 cycles (4 cycles, total)'''
 
'''3-week cycle up to 3 cycles (4 cycles, total)'''
Line 3,625: Line 3,638:
  
 
''Note: this is not the dose-adjusted R-EPOCH regimen''
 
''Note: this is not the dose-adjusted R-EPOCH regimen''
 +
====Chemotherapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV on day 1
 +
*[[Etoposide (Vepesid)]] 65 mg/m<sup>2</sup>/day (total dose of 195 mg/m2) IV continuous infusion on days 2 to 4
 +
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 14
 +
*[[Vincristine (Oncovin)]] 0.5 mg/m<sup>2</sup>/day (total dose of 1.5 mg/m2) IV continuous infusion on days 2 to 4
 +
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 5
 +
*[[Doxorubicin (Adriamycin)]] 15 mg/m<sup>2</sup>/day (total dose of 45 mg/m2) IV continuous infusion on days 2 to 4
  
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV on day 1
+
'''21-day cycle for 4 to 6 cycles'''
−
*[[Etoposide (Vepesid)]] 65 mg/m2/day (total dose of 195 mg/m2) IV continuous infusion on days 2 to 4
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2/day PO on days 1 to 14
 
−
*[[Vincristine (Oncovin)]] 0.5 mg/m2/day (total dose of 1.5 mg/m2) IV continuous infusion on days 2 to 4
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 5
 
−
*[[Doxorubicin (Adriamycin)]] 15 mg/m2/day (total dose of 45 mg/m2) IV continuous infusion on days 2 to 4
 
−
 
 
−
'''21-day cycles x 4 to 6 cycles'''
 
  
 
===References===
 
===References===
Line 3,659: Line 3,672:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once per day on days 1 & 8
+
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
*[[Dexamethasone (Decadron)]] 40 mg IV once per day on days 1 to 4
 
*[[Dexamethasone (Decadron)]] 40 mg IV once per day on days 1 to 4
−
*[[Cisplatin (Platinol)]] 25 mg/m2 IV once per day on days 1 to 3
+
*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3
  
−
'''21-day cycle x up to 6 cycles'''
+
'''21-day cycle for up to 6 cycles'''
  
 
===References===
 
===References===
Line 3,675: Line 3,688:
 
|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
R-GemOx: '''<u>R</u>'''ituximab, '''<u>Gem</u>'''citabine, '''<u>O</u>'''xaliplatin
+
R-GemOx: '''<u>R</u>'''ituximab, '''<u>Gem</u>'''citabine, '''<u>Ox</u>'''aliplatin
  
 
===Regimen #1 "GEMOX-R" {{#subobject:b976d9|Variant=1}}===
 
===Regimen #1 "GEMOX-R" {{#subobject:b976d9|Variant=1}}===
Line 3,691: Line 3,704:
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once on day 1
 +
*[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV once on day 1
  
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
'''21-day cycle for 6 to 8 cycles'''
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] 100 mg/m2 IV once on day 1
 
−
 
 
−
'''21-day cycles x 6 to 8 cycles'''
 
  
 
===Regimen #2 {{#subobject:a875bf|Variant=1}}===
 
===Regimen #2 {{#subobject:a875bf|Variant=1}}===
Line 3,712: Line 3,725:
 
|-
 
|-
 
|}
 
|}
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
====Chemotherapy====
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV at a fixed dose rate of 10 mg/m2/min once on day 2
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Oxaliplatin (Eloxatin)]] 100 mg/m2 IV over 2 hours once on day 2
+
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV at a fixed dose rate of 10 mg/m<sup>2</sup>/min once on day 2
 +
*[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV over 2 hours once on day 2
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Methylprednisolone (Solumedrol)]] 1 mg/kg IV once prior to [[Rituximab (Rituxan)]]
 
*[[Methylprednisolone (Solumedrol)]] 1 mg/kg IV once prior to [[Rituximab (Rituxan)]]
 
*[[Acetaminophen (Tylenol)]] 1000 mg PO once prior to [[Rituximab (Rituxan)]]
 
*[[Acetaminophen (Tylenol)]] 1000 mg PO once prior to [[Rituximab (Rituxan)]]
Line 3,722: Line 3,736:
 
*Primary prophylaxis with G-CSF was not permitted
 
*Primary prophylaxis with G-CSF was not permitted
  
−
'''14-day cycles x up to 8 cycles'''
+
'''14-day cycle for up to 8 cycles'''
  
 
===References===
 
===References===
Line 3,750: Line 3,764:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Ifosfamide (Ifex)]] 1,600 mg/m2 IV once per day on days 2 to 4
+
*[[Ifosfamide (Ifex)]] 1,600 mg/m<sup>2</sup> IV once per day on days 2 to 4
 
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg per cycle) IV once on day 3
 
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg per cycle) IV once on day 3
−
*[[Etoposide (Vepesid)]] 100 mg/m2 IV once per day on days 2 to 4
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 2 to 4
  
 
'''3 cycles; duration of cycles not specified in the abstract'''
 
'''3 cycles; duration of cycles not specified in the abstract'''
Line 3,782: Line 3,796:
  
 
''Third cycle intended to be followed by peripheral blood stem cell collection''
 
''Third cycle intended to be followed by peripheral blood stem cell collection''
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
====Chemotherapy====
−
**An additional one-time dose of [[Rituximab (Rituxan)]] 375 mg/m2 IV was given 48 hours before the beginning of cycle 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Ifosfamide (Ifex)]] 5,000 mg/m2 IV continuous infusion over 24 hours on day 4, mixed together with [[Mesna (Mesnex)]]
+
**An additional one-time dose of [[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV was given 48 hours before the beginning of cycle 1
 +
*[[Ifosfamide (Ifex)]] 5,000 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 4, mixed together with [[Mesna (Mesnex)]]
 
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg per cycle) IV bolus once on day 4
 
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg per cycle) IV bolus once on day 4
 
**Carboplatin AUC calculated based on a 12-hour creatinine clearance
 
**Carboplatin AUC calculated based on a 12-hour creatinine clearance
−
*[[Etoposide (Vepesid)]] 100 mg/m2 IV bolus once per day on days 3 to 5
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV bolus once per day on days 3 to 5
  
−
'''14-day cycles x 3 cycles'''
+
'''14-day cycle for 3 cycles'''
  
−
Supportive medications (as described by Kewalramani et al. 2004):
+
====Supportive medications====
−
*[[Mesna (Mesnex)]] 5,000 mg/m2 IV continuous infusion over 24 hours on day 4, mixed together with [[Ifosfamide (Ifex)]]
+
*(as described by Kewalramani et al. 2004):
 +
*[[Mesna (Mesnex)]] 5,000 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 4, mixed together with [[Ifosfamide (Ifex)]]
 
*[[Acetaminophen (Tylenol)]] 650 mg PO once as premedication for [[Rituximab (Rituxan)]]
 
*[[Acetaminophen (Tylenol)]] 650 mg PO once as premedication for [[Rituximab (Rituxan)]]
 
*[[Diphenhydramine (Benadryl)]] 50 mg IV once as premedication for [[Rituximab (Rituxan)]]
 
*[[Diphenhydramine (Benadryl)]] 50 mg IV once as premedication for [[Rituximab (Rituxan)]]
Line 3,823: Line 3,839:
 
|-
 
|-
 
|}
 
|}
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
====Chemotherapy====
−
*[[Ifosfamide (Ifex)]] 5,000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together with [[Mesna (Mesnex)]]
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 +
*[[Ifosfamide (Ifex)]] 5,000 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 2, mixed together with [[Mesna (Mesnex)]]
 
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg per cycle) IV once on day 2
 
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg per cycle) IV once on day 2
−
*[[Etoposide (Vepesid)]] 100 mg/m2 IV bolus once per day on days 2 to 4
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV bolus once per day on days 2 to 4
 
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 7
 
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 7
  
−
Supportive medications:
+
====Supportive medications====
−
*[[Mesna (Mesnex)]] 5,000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together with [[Ifosfamide (Ifex)]]
+
*[[Mesna (Mesnex)]] 5,000 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 2, mixed together with [[Ifosfamide (Ifex)]]
 
*[[Aspirin]] 81 mg PO once per day from day 1 until platelets < 50,000
 
*[[Aspirin]] 81 mg PO once per day from day 1 until platelets < 50,000
 
*Low dose LMWH for patients intolerant of [[Aspirin]]
 
*Low dose LMWH for patients intolerant of [[Aspirin]]
−
 
 
*"[[Filgrastim (Neupogen) | Granulocyte colony-stimulating factor]] was administered after R-ICE"
 
*"[[Filgrastim (Neupogen) | Granulocyte colony-stimulating factor]] was administered after R-ICE"
  
−
'''14-day cycle x 2 cycles'''
+
'''14-day cycle for 2 cycles'''
  
 
''Responders received a 3rd cycle with stem cell collection 10 to 14 days afterwards, followed by [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|autologous stem cell transplant]].''
 
''Responders received a 3rd cycle with stem cell collection 10 to 14 days afterwards, followed by [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|autologous stem cell transplant]].''
Line 3,866: Line 3,882:
  
 
''Treatment preceded by [[Diffuse_large_B-cell_lymphoma#R-MegaCHOP|R-MegaCHOP x3]]; these were patients with PET-positive disease at interim assessment.''
 
''Treatment preceded by [[Diffuse_large_B-cell_lymphoma#R-MegaCHOP|R-MegaCHOP x3]]; these were patients with PET-positive disease at interim assessment.''
 +
====Chemotherapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 +
*[[Ifosfamide (Ifex)]] 10,000 mg/m<sup>2</sup> IV continuous infusion over 72 hours on days 1 to 3
 +
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 12 hours once per day on days 1 to 3
  
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
====Supportive medications====
−
*[[Ifosfamide (Ifex)]] 10,000 mg/m2 IV continuous infusion over 72 hours on days 1 to 3
 
−
*[[Etoposide (Vepesid)]] 150 mg/m2 IV over 12 hours once per day on days 1 to 3
 
−
 
 
−
Supportive medications:
 
 
*[[Mesna (Mesnex)]] given after R-IFE; details not supplied in manuscript
 
*[[Mesna (Mesnex)]] given after R-IFE; details not supplied in manuscript
 
*[[Pegfilgrastim (Neulasta)]] given after each cycle
 
*[[Pegfilgrastim (Neulasta)]] given after each cycle
Line 3,905: Line 3,921:
  
 
''BSA was capped at 2 for all dose calculations.''
 
''BSA was capped at 2 for all dose calculations.''
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Vinorelbine (Navelbine)]] 25 mg/m2 IV once per day on days 1 & 15
+
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 15
−
*[[Ifosfamide (Ifex)]] 1,000 mg/m2 IV continuous infusion from day 1 to 5 (total dose 5,000 mg/m2)
+
*[[Ifosfamide (Ifex)]] 1,000 mg/m<sup>2</sup> IV continuous infusion from day 1 to 5 (total dose 5,000 mg/m2)
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV once on day 1
+
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 1
 
*[[Prednisone (Sterapred)]] 1 mg/kg (route not specified) once per day on days 1 to 5
 
*[[Prednisone (Sterapred)]] 1 mg/kg (route not specified) once per day on days 1 to 5
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Mesna (Mesnex)]] given with [[Ifosfamide (Ifex)]] "at the same dose"; schedule not specified in the paper
 
*[[Mesna (Mesnex)]] given with [[Ifosfamide (Ifex)]] "at the same dose"; schedule not specified in the paper
 
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 7 was recommended
 
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 7 was recommended
 
*Epoietin alpha support was recommended for Hgb < 10 g/dL
 
*Epoietin alpha support was recommended for Hgb < 10 g/dL
  
−
'''28-day cycle x 3 cycles'''
+
'''28-day cycle for 3 cycles'''
  
 
''Responders were recommended to undergo 3 additional cycles or [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|autologous stem cell transplant]].''
 
''Responders were recommended to undergo 3 additional cycles or [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|autologous stem cell transplant]].''
Line 3,944: Line 3,960:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
 
*[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once per week
 
*[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once per week
  
−
'''28-day cycles x up to 6 cycles'''
+
'''28-day cycle for up to 6 cycles'''
  
 
===References===
 
===References===
Line 3,973: Line 3,989:
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV once on day 2
 +
*[[Topotecan (Hycamtin)]] 1 mg/m<sup>2</sup> IV once per day on days 2 to 6
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
  
−
*[[Paclitaxel (Taxol)]] 200 mg/m2 IV once on day 2
+
====Supportive medications====
−
*[[Topotecan (Hycamtin)]] 1 mg/m2 IV once per day on days 2 to 6
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
 
 
−
Supportive medications:
 
 
*[[Filgrastim (Neupogen)]] 5 µg/kg SC once per day from day 7 until neutrophil recovery
 
*[[Filgrastim (Neupogen)]] 5 µg/kg SC once per day from day 7 until neutrophil recovery
 
*[[Dexamethasone (Decadron)]] 20 mg IV once 30 minutes prior to [[Paclitaxel (Taxol)]]
 
*[[Dexamethasone (Decadron)]] 20 mg IV once 30 minutes prior to [[Paclitaxel (Taxol)]]
Line 4,129: Line 4,145:
  
 
''Treatment preceded by [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|BEAM autologous transplant]].''
 
''Treatment preceded by [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|BEAM autologous transplant]].''
−
 
+
====Chemotherapy====
 
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
  
Line 4,150: Line 4,166:
  
 
''Treatment preceded by [[#Lenalidomide_.26_Rituximab|lenalidomide & rituximab]] x 4.''
 
''Treatment preceded by [[#Lenalidomide_.26_Rituximab|lenalidomide & rituximab]] x 4.''
−
 
+
====Chemotherapy====
 
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
  
−
'''28-day cycle x 8 months'''
+
'''28-day cycle for 8 months'''
  
 
===References===
 
===References===
Line 4,227: Line 4,243:
  
 
''Treatment preceded by [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|BEAM autologous stem cell transplant]], and begins on day +28.''
 
''Treatment preceded by [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|BEAM autologous stem cell transplant]], and begins on day +28.''
−
 
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once every 8 weeks
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once every 8 weeks
  
 
'''1 year course'''
 
'''1 year course'''

Revision as of 02:00, 4 July 2016

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109 regimens on this page
165 variants on this page


Untreated, pre-phase

Vincristine & Prednisone

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Regimen

Study Evidence
Pfreundschuh et al. 2004 (NHL-B2) Non-randomized

Recommended "to improve the performance status of patients and to ameliorate side-effects of the first chemotherapy cycle."

Chemotherapy

7-day course

Treatment followed immediately by CHOP.

References

  1. 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 verified protocol PubMed

Untreated, randomized data

ACVBP-R

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ACVBP-R: Adriamycin (Doxorubicin), Cyclophosphamide, Vindesine, Bleomycin, Prednisone, Rituximab

Synonyms: R-ACVBP

Structured Concept: none

Regimen

Study Evidence Comparator Efficacy Toxicity
Récher et al. 2011 (LNH03-2B) Phase III R-CHOP Improved OS Increased toxicity
Ketterer et al. 2013 (LNH03-1B) Phase III ACVBP

Chemotherapy

CNS prophylaxis

Supportive medications

  • Filgrastim (Neupogen) 300 mcg (for patients <75 kg) or 480 mcg (for patients ≥75 kg) SC once per day on days 6 to 13

14-day cycle for 4 cycles

Treatment followed in 4 weeks by methotrexate consolidation.

References

  1. Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. link to original article contains verified protocol PubMed
  2. 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. 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

CHOP

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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Synonyms: CHOP-21, ACOP, CAVP, COPA, VACP, VCAP

Structured Concept: C9549 (NCI-T), C0055598 (NCI-MT/UMLS)

Regimen #1

Study Evidence Comparator
Elias et al. 1978 Non-randomized
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) Phase III MACOP-B
m-BACOD
ProMACE-CytaBOM
Miller et al. 1998 Phase III CHOP x 3 -> RT

Chemotherapy

21-day cycle for 8 cycles

Regimen #2

Study Evidence Comparator
Pfreundschuh et al. 2004 (NHL-B1) Phase III CHOEP-14
CHOEP-21
CHOP-14
Pfreundschuh et al. 2004 (NHL-B2) Phase III CHOEP-14
CHOEP-21
CHOP-14
Verdonck et al. 2007 Phase III I-CHOP

Treatment in NHL-B2 preceded by pre-phase vincristine & prednisone.

Chemotherapy

Supportive medications (per NHL-B1 and NHL-B2):

  • At the discretion of ordering physician: Filgrastim (Neupogen) 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13

21-day cycle for 6 cycles

Radiation therapy for initial bulky disease (NHL-B2)

"Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter ≥7.5 cm) or extranodal involvement"

  • Radiation therapy, 36 Gy to areas of initial bulky disease

Regimen #3, CHOP x3 -> XRT

Study Evidence Comparator
Miller et al. 1998 Phase III CHOP x 8
Reyes et al. 2005 Phase III ACVBP

Chemotherapy

21-day cycle for 3 cycles, then followed by radiation therapy

Radiation therapy, starting 3 weeks after cycle 3 of CHOP:

  • Involved field radiation therapy, 180-200 cGy fractions, total dose of 4000-5500 cGy. Total dose was often influenced by whether patients had clinical evidence of residual disease after 4000 cGy.

Regimen #4

Study Evidence Comparator
Coiffier et al. 2002 (LNH-98.5) Phase III R-CHOP
Tilly et al. 2003 Phase III ACVBP

Chemotherapy

Supportive medications

  • Filgrastim (Neupogen) used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia

21-day cycle for 8 cycles

Regimen #5

Study Evidence Comparator Efficacy
Habermann et al. 2006 (CALGB 9793) Phase III R-CHOP Might have inferior FFS

Chemotherapy

Supportive medications

21-day cycle for 6 to 8 cycles

Patients with CR/PR proceeded to receive maintenance rituximab versus observation.

References

  1. 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. PubMed
  2. 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 verified protocol PubMed
  3. Pavlovsky S, Santarelli MT, Erazo A, Diaz Maqueo JC, Somoza N, Lluesma Goñalons M, Cervantes G, Garcia Vela EL, Corrado C, Magnasco H, et al. 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
  4. 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
    1. Update: Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. A phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate- or high-grade non-Hodgkin's lymphoma: results of SWOG-8516 (Intergroup 0067), the National High-Priority Lymphoma Study. Ann Oncol. 1994;5 Suppl 2:91-5. PubMed
    2. 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 PubMed
  5. 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
  6. 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 verified protocol PubMed
  7. 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. 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 verified protocol PubMed
    1. 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. link to original article contains protocol PubMed
    2. 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. link to original article contains verified protocol PubMed
    3. 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 (GELA). 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
  8. 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 verified protocol PubMed
  9. 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 verified protocol PubMed
  10. 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 verified protocol PubMed
  11. 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
  12. 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 (GELA). 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
  13. 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 verified protocol PubMed
    1. 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 (MInT) 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. link to original article contains protocol PubMed
  14. 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 verified protocol PubMed
  15. 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 protocol PubMed
  16. 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 verified protocol PubMed

CHOP Intensified

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CHOP-DI: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Dose Intense
I-CHOP: Intensified Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Synonyms: CHOP-14, CHOP-DI, I-CHOP

Structured Concept: none

Regimen #1

Study Evidence
Blayney et al. 2003 (CHOP-DI, SWOG 9349) Phase II

Chemotherapy

Supportive medications

14-day cycle for up to 6 cycles

Regimen #2

Study Evidence Comparator
Verdonck et al. 2007 Phase III CHOP

Chemotherapy

Supportive medications

14-day cycle for 6 cycles

Regimen #3

Study Evidence Comparator
Pfreundschuh et al. 2004 (NHL-B1) Phase III CHOEP-14
CHOEP-21
CHOP
Pfreundschuh et al. 2008 (RICOVER-60) Phase III R-CHOP-14

Pre-phase treatment

Recommended in Pfreundschuh et al. 2004, but mandatory in Pfreundschuh et al. 2008 "to improve the performance status of patients and to ameliorate side-effects of the first chemotherapy cycle." A difference was that the prednisone in Pfreundschuh et al. 2004 could be given for 5 to 7 days.

7-day course, then proceed to main CHOP-14 regimen

Main CHOP-14 regimen

Supportive medications (per Pfreundschuh et al. 2004):

  • Filgrastim (Neupogen) 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13

14-day cycle for 6 cycles; some patients in Pfreundschuh et al. 2008 received 14-day cycle for 8 cycles

Radiation therapy for initial bulky disease

"Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter =7.5 cm) or extranodal involvement"

  • Radiation therapy, 36 Gy to areas of initial bulky disease

References

  1. Blayney DW, LeBlanc ML, Grogan T, Gaynor ER, Chapman RA, Spiridonidis CH, Taylor SA, Bearman SI, Miller TP, Fisher RI; Southwest Oncology Group. 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 verified protocol PubMed
  2. 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 verified protocol PubMed
  3. 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 verified protocol PubMed
  4. 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 verified protocol PubMed
  5. 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 (DSHNHL). 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. link to original article contains verified protocol PubMed

CHOP Modified

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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study Evidence Comparator Efficacy
Bessell et al. 2003 Phase III MCOP Seems not superior

This regimen is designed for elderly patients and is of lower intensity than standard CHOP.

Chemotherapy

21-day cycle for 6 cycles

References

  1. 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 verified protocol PubMed

CNOP, MCOP

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CNOP: Cyclophosphamide, Novantrone (Mitoxantrone), Oncovin (Vincristine), Prednisone
MCOP: Mitoxantrone, Cyclophosphamide, Oncovin (Vincristine), Prednisone

Regimen

Study Evidence Comparator Efficacy
Sonneveld et al. 1990 Phase II
Pavlovsky et al. 1992 Phase III CHOP
Bessell et al. 2003 Phase III Modified CHOP Seems not superior

Chemotherapy

21-day cycle for 6 cycles

References

  1. 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 PubMed
  2. Pavlovsky S, Santarelli MT, Erazo A, Diaz Maqueo JC, Somoza N, Lluesma Goñalons M, Cervantes G, Garcia Vela EL, Corrado C, Magnasco H, et al. 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
  3. 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 verified protocol PubMed

R-CHOEP-14

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R-CHOEP-14: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone, 14-day cycles

Regimen #1

Study Evidence Comparator Efficacy Toxicity
Schmitz et al. 2012 (DSHNHL 2002-1) Phase III R-MegaCHOEP Seems not superior Decreased toxicity

Chemotherapy

14-day cycle for 8 cycles

Radiotherapy

  • 36 Gy in daily fractions "mandatory" for patients with bulky disease (any mass > 7.5cm in diameter, or extranodal involvement)

Regimen #2, with CNS prophylaxis

Study Evidence
Holte et al. 2013 Phase II

R-CHOEP portion

Supportive medications

14-day cycle for 8 cycles, followed by:

CNS Prophylaxis

Note that IT treatment was not part of prophylaxis, except that Methotrexate (MTX) 15 mg IT was allowed at time of diagnostic LP.

HiDAC portion

  • Cytarabine (Cytosar) 3000 mg/m2 IV BID for 2 days (4 doses)
    • Dose reduced to 2000 mg/m2 for patients aged 60-65 years

Followed 3 weeks later by:

HD-MTX portion

Supportive medications

One course

Radiotherapy

  • "Given at the discretion of the individual centers (36–45 Gy). Indications for giving radiotherapy after the completion of chemotherapy included bulky disease (≥10 cm) at diagnosis, localized PET-positive residual lesions, and residual disease, not eligible for biopsy at a localized site, and potentially curable by radiotherapy."

References

  1. Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, Viardot A, Bentz M, Peter N, Ehninger G, Doelken G, Ruebe C, Truemper L, Rosenwald A, Pfreundschuh M, Loeffler M, Glass B; for the German High-Grade Lymphoma Study Group (DSHNHL). Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012 Dec;13(12):1250-1259. Epub 2012 Nov 16. link to original article PubMed
  2. Holte H, Leppä S, Björkholm M, Fluge O, Jyrkkiö S, Delabie J, Sundström C, Karjalainen-Lindsberg ML, Erlanson M, Kolstad A, Fosså A, Ostenstad B, Löfvenberg E, Nordström M, Janes R, Pedersen LM, Anderson H, Jerkeman M, Eriksson M. Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study. Ann Oncol. 2013 May;24(5):1385-92. Epub 2012 Dec 17. link to original article contains verified protocol PubMed

R-CHOP

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R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Synonyms: R-CHOP-21, CHOP-R

Structured Concept: C9760 (NCI-T), C0393023 (NCI-MT/UMLS)

‘’Note: most of the variation between these regimen variants is in the dose or type of steroid.’’

Regimen #1, prednisone 100 mg/m2

Study Evidence Comparator Efficacy
Offner et al. 2015 Randomized Phase II VR-CAP Seems not superior

This regimen was used for non-germinal center B-cell (non-GCB) DLBCL.

Chemotherapy

21-day cycle for 6 cycles

Regimen #2, prednisone 40 mg/m2

Study Evidence Comparator Efficacy
Coiffier et al. 2002 (LNH-98.5) Phase III CHOP Superior OS
Delarue et al. 2013 (LNH03-6B) Phase III R-CHOP14 Seems not superior

Chemotherapy

CNS prophylaxis

As described in Delarue et al. 2013 (LNH03-6B):

Supportive medications

  • Filgrastim (Neupogen) used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia

21-day cycle for 8 cycles

Regimen #3, prednisone 100 mg, flat-dose vincristine

Study Evidence Comparator Efficacy Toxicity
Pfreundschuh et al. 2006 (MInT) Phase III CHOP Superior EFS Similar toxicity

Chemotherapy

Supportive medications

21-day cycle for 6 cycles

Regimen #4, rituximab lead-in

Study Evidence Comparator Efficacy
Habermann et al. 2006 (CALGB 9793) Phase III CHOP Might have superior FFS

Chemotherapy

Supportive medications

21-day cycle for 6 to 8 cycles

This trial also included a randomization to maintenance rituximab versus observation for responders; however an advantage was only seen in the group receiving CHOP upfront, which is no longer standard of care.

Regimen #5, prednisone 100 mg

Study Evidence Comparator Efficacy
Merli et al. 2012 (ANZINTER3) Phase III R-miniCEOP Seems not superior

Chemotherapy

Supportive medications

  • Prophylactic G-CSF used for persisting grade 4 neutropenia or febrile neutropenia.
  • Cotrimoxazole (dose/schedule not specified) prophylaxis.
  • Erythropoietin use was allowed for hemoglobin <11 g/dL.

21-day cycle for 6 cycles

Radiation therapy

"At the end of chemotherapy, radiotherapy (RT) was scheduled for sites of previous bulky disease or partially responding sites."

Regimen #6, prednisolone 40 mg/m2

Study Evidence Comparator Efficacy
Cunningham et al. 2013 Phase III R-CHOP-14 Seems not superior

Note: Cunningham et al. 2013 said that it based its regimen on Coiffier et al. 2002, but notably it uses prednisolone instead of prednisone.

Chemotherapy

CNS prophylaxis

Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:

  • Methotrexate (MTX) 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.

Supportive medications

  • Lenograstim (Granocyte) (dose/route not specified) given on days 4 to 12 at physician discretion
  • Allopurinol (Zyloprim) 300 mg PO once per day during cycle 1
  • Co-trimoxazole 480 mg (route not specified) BID on 3 days per week, taken throughout therapy, ending 2 weeks after chemotherapy is completed

21-day cycle for 8 cycles

Regimen #7, short-course for early stage DLBCL

Study Evidence
Persky et al. 2008 (SWOG S0014) Phase II

Chemotherapy

21-day cycle for 3 cycles, followed by:

Radiation therapy

Involved-field radiation therapy to begin 3 weeks after last cycle of R-CHOP, see paper for details.

Regimen #8, primary testicular DLBCL

Study Evidence
Vitolo et al. 2011 (IELSG-10) Phase II

This regimen is for primary testicular lymphoma. All patients had a diagnostic orchiectomy prior to starting chemotherapy.

Chemotherapy

CNS prophylaxis

21-day cycle for 6 cycles (up to 8 cycles for stage II patients), followed by:

Radiation therapy

25 to 30 Gy to the contralateral testis. For patients with stage II disease, involved-field radiation therapy was added, see paper for details.

References

  1. 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. 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 verified protocol PubMed
    1. 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. link to original article contains protocol PubMed
    2. 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. link to original article contains verified protocol PubMed content property of HemOnc.org
    3. 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 (GELA). 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
  2. 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 verified protocol PubMed
    1. 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 (MInT) 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. link to original article contains protocol PubMed
  3. 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 verified protocol PubMed
  4. Persky DO, Unger JM, Spier CM, Stea B, LeBlanc M, McCarty MJ, Rimsza LM, Fisher RI, Miller TP; Southwest Oncology Group. Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. J Clin Oncol. 2008 May 10;26(14):2258-63. Epub 2008 Apr 14. link to original article contains verified protocol PubMed
  5. Vitolo U, Chiappella A, Ferreri AJ, Martelli M, Baldi I, Balzarotti M, Bottelli C, Conconi A, Gomez H, Lopez-Guillermo A, Martinelli G, Merli F, Novero D, Orsucci L, Pavone V, Ricardi U, Storti S, Gospodarowicz MK, Cavalli F, Sarris AH, Zucca E. First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, CNS prophylaxis, and contralateral testis irradiation: final results of an international phase II trial. J Clin Oncol. 2011 Jul 10;29(20):2766-72. Epub 2011 Jun 6. link to original article contains verified protocol PubMed
  6. Merli F, Luminari S, Rossi G, Mammi C, Marcheselli L, Tucci A, Ilariucci F, Chiappella A, Musso M, Di Rocco A, Stelitano C, Alvarez I, Baldini L, Mazza P, Salvi F, Arcari A, Fragasso A, Gobbi PG, Liberati AM, Federico M. Cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab versus epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab for the initial treatment of elderly "fit" patients with diffuse large B-cell lymphoma: results from the ANZINTER3 trial of the Intergruppo Italiano Linfomi. Leuk Lymphoma. 2012 Apr;53(4):581-8. Epub 2011 Nov 15. link to original article contains verified protocol PubMed
  7. Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. link to original article PubMed
  8. Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, Bologna S, Ghesquières H, Hacini M, Fruchart C, Ysebaert L, Fermé C, Casasnovas O, Van Hoof A, Thyss A, Delmer A, Fitoussi O, Molina TJ, Haioun C, Bosly A. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):525-33. Epub 2013 Apr 9. link to original article contains verified protocol PubMed
  9. Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. link to original article contains verified protocol PubMed
  10. Oki Y, Westin JR, Vega F, Chuang H, Fowler N, Neelapu S, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale M, Younes A, Rodriguez MA, Orlowski RZ, Wang M, Ouzounian ST, Samaniego F, Fayad L. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol. 2013 Dec;163(5):611-20. Epub 2013 Oct 1. link to original article contains verified protocol PubMed
  11. Seymour JF, Pfreundschuh M, Trnený M, Sehn LH, Catalano J, Csinady E, Moore N, Coiffier B; MAIN Study Investigators. R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: final MAIN study outcomes. Haematologica. 2014 Aug;99(8):1343-9. Epub 2014 Jun 3. link to original article PubMed
  12. Retrospective: Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. link to original article PubMed
  13. Offner F, Samoilova O, Osmanov E, Eom HS, Topp MS, Raposo J, Pavlov V, Ricci D, Chaturvedi S, Zhu E, van de Velde H, Enny C, Rizo A, Ferhanoglu B. Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL. Blood. 2015 Oct 15;126(16):1893-901. Epub 2015 Jul 31. link to original article link to PMC article contains verified protocol PubMed

R-CHOP Intensified

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R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Synonyms: R-CHOP-14, Dose-dense rituximab-CHOP

Structured Concept: none

Regimen #1

Study Evidence Comparator
Pfreundschuh et al. 2014 (SEXIE-R-CHOP-14) Randomized Phase II See below

Main CHOP-14 portion

Rituximab portion

Two arms were assessed; results are pending from this comparison. These higher doses were for males, only.

OR

14-day cycle for 6 cycles (8 doses of rituximab regardless of total number of CHOP-14 cycles)

Regimen #2

Study Evidence Comparator Efficacy
Delarue et al. 2013 (LNH03-6B) Phase III R-CHOP21 Seems not superior

Chemotherapy

CNS prophylaxis

Supportive medications

14-day cycle for 8 cycles

Regimen #3

Study Evidence Comparator Efficacy
Cunningham et al. 2013 Phase III R-CHOP-21 Seems not superior

Main R-CHOP-14 portion

CNS prophylaxis

Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:

  • Methotrexate (MTX) 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.

Supportive medications

  • Lenograstim (Granocyte) (dose/route not specified) given on days 4 to 12
  • Allopurinol (Aloprim) 300 mg PO once per day during cycle 1
  • Co-trimoxazole 480 mg (route not specified) BID on 3 days per week, taken throughout therapy, ending 2 weeks after treatment is completed

14-day cycle for 6 cycles; then give additional doses of rituximab as described below

Additional doses of Rituximab

14-day cycle for 2 cycles

Regimen #4

Study Evidence Comparator Efficacy
Pfreundschuh et al. 2008 (RICOVER-60) Phase III CHOP-14 x 6 Superior OS
CHOP-14 x 8
R-CHOP-14 x 8

Pre-phase treatment

7-day course, then proceed to main R-CHOP-14 regimen

Main regimen

Supportive medications

14-day cycle for 6 to 8 cycles (8 doses of rituximab regardless of total number of cycles)

Radiation therapy for initial bulky disease

"Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter =7.5 cm) or extranodal involvement"

  • Radiation therapy, 36 Gy to areas of initial bulky disease

Regimen #5

Study Evidence
Pfreundschuh et al. 2014 (SMARTE-R-CHOP-14) Phase II

Pre-phase treatment

7-day course, then proceed to main SMARTE-R-CHOP-14 regimen

Main regimen

Supportive medications

14-day cycle for 6 cycles

Radiation therapy for initial bulky disease

"Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter =7.5 cm) or extranodal involvement"

  • Radiation therapy, 36 Gy to areas of initial bulky disease

References

  1. 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 (DSHNHL). 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. link to original article contains verified protocol PubMed
  2. Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, Bologna S, Ghesquières H, Hacini M, Fruchart C, Ysebaert L, Fermé C, Casasnovas O, Van Hoof A, Thyss A, Delmer A, Fitoussi O, Molina TJ, Haioun C, Bosly A. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):525-33. Epub 2013 Apr 9. link to original article contains verified protocol PubMed
  3. Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. link to original article contains verified protocol PubMed
  4. Abstract: Michael Pfreundschuh, Gerhard Held, Samira Zeynalova, Carsten Zwick, Mathias Haenel, Lorenz Truemper, Martin H. Dreyling, Judith Dierlamm, Markus Loeffler, Norbert Schmitz, Niels Murawski, German High-Grad Non-Hodgkin Lymphoma Study Group (DSHNHL). Increased rituximab (R) doses and effect on risk of elderly male patients with aggressive CD20+ B-cell lymphomas: Results from the SEXIE-R-CHOP-14 trial of the DSHNHL. J Clin Oncol 32:5s, 2014 (suppl; abstr 8501) link to original abstract
  5. Pfreundschuh M, Poeschel V, Zeynalova S, Hänel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N. Optimization of Rituximab for the Treatment of Diffuse Large B-Cell Lymphoma (II): Extended Rituximab Exposure Time in the SMARTE-R-CHOP-14 Trial of the German High-Grade Non-Hodgkin Lymphoma Study Group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. Epub 2014 Nov 17. Erratum in: J Clin Oncol. 2015 Jun 10;33(17):1991. link to original article contains verified protocol PubMed

R-CVP

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R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone

Structured Concept: C63473 (NCI-T), C1882520 (NCI-MT/UMLS)

Regimen

Chemotherapy

21-day cycle for up to 8 cycles

References

See references for CVP

R-HyperCVAD/R-MA

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R-HCVAD: Rituximab, Hyperfractionated Cyclophosphamide, Vincristine, Adriamycin (Doxorubicin), Dexamethasone
R-MA: Rituximab, Methotrexate, Ara-C (Cytarabine)

Regimen

Study Evidence Comparator Efficacy
Oki et al. 2013 Phase III R-CHOP Seems to have increased CRR

Intended for high-risk DLBCL (IPI ≥3). The authors report "excellent outcome" in patients ≤45 years old, however patients >45 years old had "unacceptable mortality."

Part A (cycles 1, 3, 5)

Supportive medications

Dose modifications

  • Vincristine (Oncovin) reduced once by 50% for NCI common toxicity criteria Grade 2+ peripheral neuropathy, omitted if Grade 2+ peripheral neuropathy persists
  • Doxorubicin (Adriamycin) and Cyclophosphamide (Cytoxan) reduced by 20% in subsequent A cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC <0.75 × 10^9/L or platelet count <75 × 10^9/L on day 21

Next cycle to start once ANC count is ≥1 x 10^9/L and platelet count is ≥100 x 10^9/L.

Although the protocol does not specify, it is assumed that if these thresholds are not met by day 21, the next cycle will start with the dose reductions as specified.

Part B (cycles 2, 4, 6)

Supportive medications

Dose modifications

  • Methotrexate (MTX) reduced by 25% in subsequent B cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC < 0.75 × 10^9/L or platelet count < 75 × 10^9/L on day 21
  • Cytarabine (Cytosar) reduced by 33% in subsequent B cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC < 0.75 × 10^9/L or platelet count < 75 × 10^9/L on day 21

21-day cycles

====CNS prophylaxis==== "recommended in patients with paraspinal disease, paranasal sinus disease, testicular disease, bone marrow disease, diffuse osseous disease or ≥2 sites of extranodal disease. Actual administration of prophylactic intrathecal chemotherapy was at the treating physician's discretion."

References

  1. Oki Y, Westin JR, Vega F, Chuang H, Fowler N, Neelapu S, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale M, Younes A, Rodriguez MA, Orlowski RZ, Wang M, Ouzounian ST, Samaniego F, Fayad L. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol. 2013 Dec;163(5):611-20. Epub 2013 Oct 1. link to original article contains verified protocol PubMed
  2. Retrospective: Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. link to original article PubMed

R-miniCEOP

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R-miniCEOP: Rituximab, mini, Cyclophosphamide, Epirubicin, O?? (vinblastine), Prednisone

Regimen

Study Evidence Comparator Efficacy
Merli et al. 2012 (ANZINTER3) Phase III R-CHOP Equivalent RR

Chemotherapy

Supportive medications

  • Prophylactic G-CSF used for persisting grade 4 neutropenia or febrile neutropenia.
  • Cotrimoxazole (dose/route/schedule not specified) prophylaxis.
  • Erythropoietin use was allowed for hemoglobin <11 g/dL.

21-day cycle for 6 cycles

Radiation therapy

"At the end of chemotherapy, radiotherapy (RT) was scheduled for sites of previous bulky disease or partially responding sites."

References

  1. Merli F, Luminari S, Rossi G, Mammi C, Marcheselli L, Tucci A, Ilariucci F, Chiappella A, Musso M, Di Rocco A, Stelitano C, Alvarez I, Baldini L, Mazza P, Salvi F, Arcari A, Fragasso A, Gobbi PG, Liberati AM, Federico M. Cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab versus epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab for the initial treatment of elderly "fit" patients with diffuse large B-cell lymphoma: results from the ANZINTER3 trial of the Intergruppo Italiano Linfomi. Leuk Lymphoma. 2012 Apr;53(4):581-8. Epub 2011 Nov 15. link to original article contains verified protocol PubMed

Untreated, non-randomized or retrospective data

CHOP -> IFRT -> Ibritumomab tiuxetan

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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study Evidence
Persky et al. 2014 (SWOG S0313) Phase II

This regimen is intended for limited-stage aggressive B-cell NHL; the majority of patients studied had DLBCL.

Chemotherapy

21-day cycle for 3 cycles, followed by:

Radiation therapy

Involved-field radiation therapy to begin 3 weeks after last cycle of CHOP, see paper for details.

Complete course followed in 3 to 6 weeks by:

Consolidation radioimmunotherapy

References

  1. 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 verified protocol PubMed

DA-R-EPOCH

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DA-R-EPOCH: Dose Adjusted Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)

Synonyms: DA-EPOCH-R, EPOCH-R, REPOCH

Structured Concept: C63461 (NCI-T), C1882521 (NCI-MT/UMLS)

Regimen

Study Evidence
García-Suárez et al. 2007 Phase II
Wilson et al. 2008 Phase II
Wilson et al. 2012 Phase II
Purroy et al. 2014 Phase II

Chemotherapy

Supportive medications

21-day cycle for 6 to 8 cycles

Dose modifications

  • Start cycle 1 as described above.
  • Obtain CBCs twice per week for nadir measurements.
  • If nadir ANC >500, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
  • If nadir ANC <500 on 1 or 2 measurements, use same doses as last cycle.
  • If nadir ANC <500 on at least 3 measurements, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
  • And/or if nadir platelet count <25 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.
  • Can start new cycle every 21 days if ANC >1,000 and platelets >100. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.

References

  1. García-Suárez J, Bañas H, Arribas I, De Miguel D, Pascual T, Burgaleta C. Dose-adjusted EPOCH plus rituximab is an effective regimen in patients with poor-prognostic untreated diffuse large B-cell lymphoma: results from a prospective observational study. Br J Haematol. 2007 Jan;136(2):276-85. link to original article contains verified protocol PubMed
  2. Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, Raffeld M, Gutierrez M, Chabner BA, Staudt L, Jaffe ES, Janik JE. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008 Jun 1;26(16):2717-24. link to original article PubMed
  3. Wilson WH, Jung SH, Porcu P, Hurd D, Johnson J, Martin SE, Czuczman M, Lai R, Said J, Chadburn A, Jones D, Dunleavy K, Canellos G, Zelenetz AD, Cheson BD, Hsi ED; Cancer Leukemia Group B. A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. Haematologica. 2012 May;97(5):758-65. Epub 2011 Dec 1. link to original article PubMed
  4. Purroy N, Bergua J, Gallur L, Prieto J, Lopez LA, Sancho JM, García-Marco JA, Castellví J, Montes-Moreno S, Batlle A, de Villambrosia SG, Carnicero F, Ferrando-Lamana L, Piris MA, Lopez A. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma. A phase II study conducted by the Spanish PETHEMA Group. Br J Haematol. 2015 Apr;169(2):188-98. Epub 2014 Dec 18. link to original article contains protocol PubMed
  5. Retrospective: Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. link to original article PubMed

Helicobacter pylori eradication therapy

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Regimen

This regimen is intended for the treatment of gastric DLBCL only; H. pylori eradication would not be an appropriate treatment for systemic DLBCL.

Before 1996:

After 1996:

References

  1. Kuo SH, Yeh KH, Wu MS, Lin CW, Hsu PN, Wang HP, Chen LT, Cheng AL. Helicobacter pylori eradication therapy is effective in the treatment of early-stage H pylori-positive gastric diffuse large B-cell lymphomas. Blood. 2012 May 24;119(21):4838-44; quiz 5057. Epub 2012 Mar 7. link to original article PubMed

R-CDOP, DRCOP

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R-CDOP: Rituximab, Cyclophosphamide, Doxil (Pegylated liposomal doxorubicin), Oncovin (Vincristine), Prednisone
DRCOP: Doxil (Pegylated liposomal doxorubicin), Rituximab, Cyclophosphamide, Oncovin (Vincristine), Prednisone

Regimen #1

Study Evidence
Oki et al. 2014 Phase II

Chemotherapy

Supportive medications

OR

Dose modifications

21-day cycle for 6 to 8 cycles

Regimen #2

Study Evidence
Zaja et al. 2006 Phase II

Only the dose of liposomal doxorubicin and number of cycles used was specified in the abstract. The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.

Chemotherapy

21-day cycle for 6 cycles

References

  1. Zaja F, Tomadini V, Zaccaria A, Lenoci M, Battista M, Molinari AL, Fabbri A, Battista R, Cabras MG, Gallamini A, Fanin R. CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2006 Oct;47(10):2174-80. link to original article PubMed
  2. Oki Y, Ewer MS, Lenihan DJ, Fisch MJ, Hagemeister FB, Fanale M, Romaguera J, Pro B, Fowler N, Younes A, Astrow AB, Huang X, Kwak LW, Samaniego F, McLaughlin P, Neelapu SS, Wang M, Fayad LE, Durand JB, Rodriguez MA. Pegylated liposomal doxorubicin replacing conventional doxorubicin in standard R-CHOP chemotherapy for elderly patients with diffuse large B-cell lymphoma: an open label, single arm, phase II trial. Clin Lymphoma Myeloma Leuk. 2015 Mar;15(3):152-8. Epub 2014 Sep 28. link to original article link to PMC article contains verified protocol PubMed

R-CEOP90 (Epirubicin)

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R-CEOP90: Rituximab, Cyclophosphamide, Epirubicin (90 mg/m2 dosing), Oncovin (Vincristine), Prednisone

Regimen

Study Evidence
Cai et al. 2014 Phase II

This regimen is intended to reduce cardiotoxicity and was not just for patients with contraindicated doxorubicin. Note that the cycle length is not explicitly defined in the paper but was reported as a median of 21 days (range 21 to 33 days).

Chemotherapy

21-day cycle for 4 cycles followed by involved field radiotherapy (30-45 Gy) of bulky disease and extranodal and residual masses for patients with stage IA or IIA disease; 6 cycles for all others

References

  1. Cai QC, Gao Y, Wang XX, Cai QQ, Lin ZX, Bai B, Guo Y, Huang HQ. Long-term results of the R-CEOP90 in the treatment of young patients with chemotherapy-naïve diffuse large B cell lymphoma: a phase II study. Leuk Lymphoma. 2014 Oct;55(10):2387-8. link to original article contains verified protocol PubMed

R-CEOP (Etoposide)

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R-CEOP: Rituximab, Cyclophosphamide, Etoposide, Oncovin (Vincristine), Prednisone

Regimen

Study Evidence
Moccia et al. 2009 Retrospective

This regimen is intended for patients with a contraindication to anthracyclines. Only the dose of etoposide and number of cycles used was specified in the abstract. The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.

Chemotherapy

21-day cycle for 3 to 4 cycles +/- radiation therapy for patients with limited stage disease; 6 cycles for patients with advanced stage disease

References

  1. Retrospective: Abstract: Moccia, Alden A., Schaff, Kimberly, Hoskins, Paul, Klasa, Richard, Savage, Kerry J., Shenkier, Tamara, Gascoyne, Randy D., Connors, Joseph M., Sehn, Laurie H. R-CHOP with Etoposide Substituted for Doxorubicin (R-CEOP): Excellent Outcome in Diffuse Large B Cell Lymphoma for Patients with a Contraindication to Anthracyclines. ASH Annual Meeting Abstracts 2009 114: 408 link to abstract

R-CHMP

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R-CHMP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Marqibo (Vincristine liposomal), Prednisone

Regimen

Study Evidence
Hagemeister et al. 2013 Phase II

Chemotherapy

21-day cycle for 6 cycles; stage I patients with no LN > 5 cm received 3 cycles followed by local XRT

References

  1. 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 verified protocol PubMed

R-CHOP -> Ibritumomab tiuxetan

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R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study Evidence
Witzig et al. 2015 (ECOG3402) Phase II

This regimen is intended for stage I-II DLBCL based on CT (not PET-CT) imaging.

Chemotherapy

21-day cycle for 4 to 6 cycles, followed in 3 to 12 weeks by:

Consolidation radioimmunotherapy

Patients with CT or PET positive disease 12 weeks after radioimmunotherapy underwent 30 Gy of IFRT.

References

  1. Witzig TE, Hong F, Micallef IN, Gascoyne RD, Dogan A, Wagner H Jr, Kahl BS, Advani RH, Horning SJ. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402. Br J Haematol. 2015 Sep;170(5):679-86. Epub 2015 May 14. link to original article contains verified protocol PubMed

R-GCVP

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R-GCVP: Rituximab, Gemcitabine, Cyclophosphamide, Vincristine, Prednisolone

Regimen

Study Evidence
Fields et al. 2013 Phase II

Intended for use in patients unlikely to tolerate anthracyclines due to cardiac comorbidity.

Chemotherapy

Supportive medications

CNS prophylaxis

  • Methotrexate (MTX) 12.5 mg IT x 3 cycles (timing not specified) for patients at high risk of CNS relapse

21-day cycle for 6 cycles

References

  1. Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P, Jack A, El-Mehidi N, Johnson PW, Radford J, Linch DC, Cunnningham D. De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United kingdom national cancer research institute trial. J Clin Oncol. 2014 Feb 1;32(4):282-7. Epub 2013 Nov 12. link to original article contains verified protocol PubMed

R-MegaCHOP

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R-MegaCHOP: Rituximab, Mega, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study Evidence
Pardal et al. 2014 Phase II

Chemotherapy

Supportive medications

21-day cycle for 3 cycles

Patients with a negative PET-CT after 3 cycles received another 3 cycles of R-MegaCHOP for a total of 6 cycles; others underwent intensification of treatment with R-IFE.

References

  1. Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. link to original article contains verified protocol PubMed

R-miniCHOP

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R-miniCHOP: Rituximab, mini, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study Evidence
Peyrade et al. 2011 Phase II

Chemotherapy

Supportive medications

  • "Prevention of tumour lysis syndrome by alkalinisation or hypouricaemic drugs was done if necessary."
  • Serotonin (5-HT3) antagonist given every cycle.
  • Prophylactic G-CSF or erythropoietin was left to treating physician's discretion.
    • Patients with severe neutropenia or neutropenic fever received G-CSF (dose not specified) SQ on days 6 to 13 of the subsequent cycle until neutrophils were = 1.0 x 109/L.

21-day cycle for 6 cycles

References

  1. Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S, Coiffier B, Haioun C, Bologna S, Fitoussi O, Lepeu G, Fruchart C, Bordessoule D, Blanc M, Delarue R, Janvier M, Salles B, André M, Fournier M, Gaulard P, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte (GELA) investigators. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2011 May;12(5):460-8. link to original article contains verified protocol PubMed

R2CHOP, LR-CHOP-21

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R2CHOP: Rituximab, Revlimid (Lenalidomide), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

LR-CHOP-21: Lenalidomide, Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen #1

Study Evidence
Vitolo et al. 2014 (REAL07) Phase II

Chemotherapy

CNS prophylaxis

Supportive medications

21-day cycle for 6 cycles

Regimen #2

Study Evidence
Nowakowski et al. 2014 Phase II

Chemotherapy

Supportive medications

21-day cycle for up to 6 cycles

Regimen #3

Study Evidence
Chiappella et al. 2013 Phase II

Chemotherapy

Supportive medications

21-day cycle for 6 cycles

References

  1. Nowakowski GS, LaPlant B, Habermann TM, Rivera CE, Macon WR, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Klebig RR, Reeder CB, Witzig TE. Lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial chemotherapy for aggressive B-cell lymphomas: phase I study. Leukemia. 2011 Dec;25(12):1877-81. Epub 2011 Jul 1. link to original article contains verified protocol PubMed
  2. Chiappella A, Tucci A, Castellino A, Pavone V, Baldi I, Carella AM, Orsucci L, Zanni M, Salvi F, Liberati AM, Gaidano G, Bottelli C, Rossini B, Perticone S, De Masi P, Ladetto M, Ciccone G, Palumbo A, Rossi G, Vitolo U. Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated elderly diffuse large B-cell lymphoma patients: phase I study by the Fondazione Italiana Linfomi. Haematologica. 2013 Nov;98(11):1732-8. Epub 2013 Jun 28. link to original article contains verified protocol PubMed
  3. Vitolo U, Chiappella A, Franceschetti S, Carella AM, Baldi I, Inghirami G, Spina M, Pavone V, Ladetto M, Liberati AM, Molinari AL, Zinzani P, Salvi F, Fattori PP, Zaccaria A, Dreyling M, Botto B, Castellino A, Congiu A, Gaudiano M, Zanni M, Ciccone G, Gaidano G, Rossi G; on behalf of the Fondazione Italiana Linfomi. Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):730-7. Epub 2014 May 12. link to original article contains verified protocol PubMed
  4. Nowakowski GS, LaPlant B, Macon WR, Reeder CB, Foran JM, Nelson GD, Thompson CA, Rivera CE, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Gascoyne RD, Habermann TM, Witzig TE. Lenalidomide Combined With R-CHOP Overcomes Negative Prognostic Impact of Non-Germinal Center B-Cell Phenotype in Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Phase II Study. J Clin Oncol. 2015 Jan 20;33(3):251-7. Epub 2014 Aug 18. link to original article contains verified protocol PubMed

VR-CHOP

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VR-CHOP: Velcade (Bortezomib), Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study Evidence
Ruan et al. 2010 Phase II

Doses here are the phase II dose of bortezomib and the R-CHOP protocol as specified in the phase I report by Furman et al. 2010

Chemotherapy

Supportive medications

21-day cycle for 6 cycles

References

  1. 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 verified protocol PubMed

Consolidation and/or maintenance after upfront therapy

Cytarabine (Cytosar)

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Regimen

Study Evidence
Récher et al. 2011 (LNH03-2B) Non-randomized
Ketterer et al. 2013 (LNH03-1B) Non-randomized

Treatment preceded by REI consolidation x 4.

Chemotherapy

14-day cycle for 2 cycles

References

  1. Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. link to original article contains verified protocol PubMed
  2. 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. 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

Methotrexate (MTX)

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Regimen

Study Evidence
Récher et al. 2011 (LNH03-2B) Non-randomized
Ketterer et al. 2013 (LNH03-1B) Non-randomized

Treatment preceded by ACVBP-R x 4.

Chemotherapy

Supportive medications

14-day cycle for 2 cycles

Treatment followed in 2 weeks by REI consolidation.

References

  1. Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. link to original article contains verified protocol PubMed
  2. 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. 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

Observation

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Regimen

Study Evidence Comparator Efficacy
Jaeger et al. 2015 (NHL13) Phase III Rituximab Seems not superior
Witzens-Harig et al. 2015 (HD2002) Phase III Rituximab Inferior OS in males

No further treatment, also variously termed "observation" and "watchful waiting". Preceded by "standard treatment" in HD2002.

References

  1. 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 verified protocol PubMed
  2. 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
  3. Jaeger U, Trneny M, Melzer H, Praxmarer M, Nawarawong W, Ben Yehuda D, Goldstein D, Mihaljevic B, Ilhan O, Ballova V, Hedenus M, Hsiao LT, Au WY, Burgstaller S, Weidinger G, Keil F, Dittrich C, Skrabs C, Klingler A, Chott A, Fridrik MA, Greil R. Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial. Haematologica. 2015 Jul;100(7):955-63. Epub 2015 Apr 24. link to original article contains verified protocol PubMed
  4. Witzens-Harig M, Benner A, McClanahan F, Klemmer J, Brandt J, Brants E, Rieger M, Meissner J, Hensel M, Neben K, Dreger P, Lengfelder E, Schmidt-Wolf I, Krämer A, Ho AD. Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma. Results of the HD2002 prospective multicentre randomized phase III trial. Br J Haematol. 2015 Dec;171(5):710-9. Epub 2015 Oct 9. link to original article PubMed

REI

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REI: Rituximab, Etoposide, Ifosfamide

Regimen

Study Evidence
Récher et al. 2011 (LNH03-2B) Non-randomized
Ketterer et al. 2013 (LNH03-1B) Non-randomized

Treatment preceded by methotrexate consolidation x 2.

Chemotherapy

14-day cycle for 4 cycles

Treatment followed in 2 weeks by cytarabine consolidation.

References

  1. Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. link to original article contains verified protocol PubMed
  2. 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. 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

Rituximab (Rituxan)

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Regimen #1

Study Evidence Comparator Efficacy
Jaeger et al. 2015 (NHL13) Phase III Observation Seems not superior

Treatment preceded by 8 infusions of rituximab (375 mg/m2) and 4 to 8 cycles of CHOP-like chemotherapy. Patients required to be in CR or CRu prior to enrollment. The protocol was amended after the first 69 patients enrolled to increase length of treatment from 1 to 2 years.

Chemotherapy

1 to 2 year course

Regimen #2

Study Evidence Comparator Efficacy
Witzens-Harig et al. 2015 (HD2002) Phase III Observation Superior OS in males

Preceded by "standard treatment" which was not further described in the paper, beyond that a majority of patient received R-CHOP (see Tables).

Chemotherapy

2 year course

References

  1. 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 verified protocol PubMed
  2. 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
  3. Jaeger U, Trneny M, Melzer H, Praxmarer M, Nawarawong W, Ben Yehuda D, Goldstein D, Mihaljevic B, Ilhan O, Ballova V, Hedenus M, Hsiao LT, Au WY, Burgstaller S, Weidinger G, Keil F, Dittrich C, Skrabs C, Klingler A, Chott A, Fridrik MA, Greil R. Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial. Haematologica. 2015 Jul;100(7):955-63. Epub 2015 Apr 24. link to original article contains verified protocol PubMed
  4. Witzens-Harig M, Benner A, McClanahan F, Klemmer J, Brandt J, Brants E, Rieger M, Meissner J, Hensel M, Neben K, Dreger P, Lengfelder E, Schmidt-Wolf I, Krämer A, Ho AD. Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma. Results of the HD2002 prospective multicentre randomized phase III trial. Br J Haematol. 2015 Dec;171(5):710-9. Epub 2015 Oct 9. link to original article contains verified protocol PubMed

Relapsed/refractory, randomized data

DHAP

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DHAP: Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study Evidence Comparator
Velasquez et al. 1988 Phase II
Philip et al. 1995 (PARMA) Phase III DHAP x 2 -> BEAC

Chemotherapy

  • Dexamethasone (Decadron) 40 mg IV over 15 minutes once per day on days 1 to 4
  • Cytarabine (Cytosar) as follows:
    • Patients younger than 70: 2000 mg/m2 IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
    • Patients older than 70: 1000 mg/m2 IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
  • Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1

Supportive medications

3 to 4 week cycle "according to the extent of myelosuppression"

Velasquez et al. 1988 report 6 to 10 courses, usually 4 courses beyond maximum response. The PARMA trial collected bone marrow after cycle 1 and then randomized responders (PR/CR) after cycle 2 to 4 more courses of DHAP versus autologous stem-cell transplant (ASCT).

References

  1. Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, et al. 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 verified protocol PubMed
  2. Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. 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 protocol PubMed

ESHAP

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ESHAP: Etoposide, Solumedrol (Methylprednisolone) High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study Evidence Comparator Efficacy
Velasquez et al. 1994 Phase III ESHA Superior RR
Avilés et al. 2010 Phase III R-ESHAP Seems not superior

Chemotherapy

Supportive medications

21 to 28 day cycles ("after recovery of the toxic effects") x 6 to 8 cycles

References

  1. 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 verified protocol PubMed
  2. 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

Gemcitabine (Gemzar)

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Regimen

Study Evidence Comparator
Fosså et al. 1999 Phase II
Pettengell et al. 2012 Phase III, <20 in this arm Pixantrone

Chemotherapy

  • Gemcitabine (Gemzar) as follows:
    • Cycle 1: 1250 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
    • Subsequent cycles (if no hematologic or nonhematologic toxicities): Optional increase to 1500 mg/m2 IV over 30 minutes once per day on days 1, 8, 15

4-week cycles until progression or intolerance

References

  1. Fosså A, Santoro A, Hiddemann W, Truemper L, Niederle N, Buksmaui S, Bonadonna G, Seeber S, Nowrousian MR. Gemcitabine as a single agent in the treatment of relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3786-92. link to original article contains verified protocol PubMed
  2. Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains protocol PubMed

Ifosfamide (Ifex)

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Regimen

Study Evidence Comparator
Case et al. 1991 (CALGB 8552) Phase II
Pettengell et al. 2012 Phase III, <20 in this arm Pixantrone

Dose & schedule is as given in Pettengell et al. CALGB 8552 used a different dose & schedule.

Chemotherapy

Supportive medications

28-day cycles

References

  1. Case DC Jr, Anderson J, Ervin TJ, Gottlieb A. Phase II trial of ifosfamide and mesna in previously treated patients with non-Hodgkin's lymphoma: Cancer and Leukemia Group B study 8552. Hematol Oncol. 1991 Jul-Oct;9(4-5):189-96. PubMed
  2. Review: Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82. Review. link to original article PubMed
  3. Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed

Oxaliplatin (Eloxatin)

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Regimen

Study Evidence Comparator
Germann et al. 1999 Phase II
Oki et al. 2005 Phase II
Pettengell et al. 2012 Phase III, <20 in this arm Pixantrone

Germann et al. give a range of 100 to 130 mg/m2; Oki et al. used the 130 mg/m2 dosage; Pettengell et al. used the 100 mg/m2 dosage.

Chemotherapy

21-day cycles

References

  1. Germann N, Brienza S, Rotarski M, Emile JF, Di Palma M, Musset M, Reynes M, Soulié P, Cvitkovic E, Misset JL. Preliminary results on the activity of oxaliplatin (L-OHP) in refractory/recurrent non-Hodgkin's lymphoma patients. Ann Oncol. 1999 Mar;10(3):351-4. link to original article contains verified protocol PubMed
  2. Review: Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82. Review. link to original article PubMed
  3. Oki Y, McLaughlin P, Pro B, Hagemeister FB, Bleyer A, Loyer E, Younes A. Phase II study of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma. Cancer. 2005 Aug 15;104(4):781-7. link to original article contains verified protocol PubMed
  4. Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed

Pixantrone (Pixuvri)

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Regimen

Study Evidence Comparator Efficacy
Pettengell et al. 2012 Phase III Etoposide
Gemcitabine
Ifosfamide
Mitoxantrone
Oxaliplatin
Vinorelbine 		Seems to have superior RR

Chemotherapy

28-day cycle for up to 6 cycles

References

  1. Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed

R-DHAP

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R-DHAP: Rituximab, Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen #1

Study Evidence Comparator Efficacy
Crump et al. 2014 (NCIC-CTG LY.12) Phase III R-GDP Noninferior RR

Chemotherapy

21-day cycle for up to 3 cycles

Responders proceeded to stem-cell mobilization and autologous stem cell transplant.

Regimen #2

Study Evidence Comparator Efficacy
Gisselbrecht et al. 2010 (CORAL) Phase III R-ICE Seems not superior

Note: the paper makes reference to Velasquez et al. 1988 to describe this regimen, although this reference is for DHAP, not R-DHAP. The paper also contains the following regimen information:

Chemotherapy

Supportive medications

  • G-CSF "depending on site policy, with R-DHAP, but always after the third cycle until the end of leukaphereses"

21-day cycle for 3 cycles

Patients with complete or partial response then received BEAM autologous stem-cell transplant.

References

  1. Hagberg H, Gisselbrecht C; CORAL study group. Randomised phase III study of R-ICE versus R-DHAP in relapsed patients with CD20 diffuse large B-cell lymphoma (DLBCL) followed by high-dose therapy and a second randomisation to maintenance treatment with rituximab or not: an update of the CORAL study. Ann Oncol. 2006 May;17 Suppl 4:iv31-2. link to original article PubMed
  2. Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. link to original article contains verified protocol PubMed
  3. Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains verified protocol PubMed

R-ESHAP

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R-ESHAP: Rituximab, Etoposide, Solumedrol (Methylprednisolone) High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study Evidence Comparator Efficacy
Martín et al. 2008 Retrospective
Avilés et al. 2010 Phase III ESHAP Seems not superior

Regimen details are based on ESHAP paper from 1994. Per retrospective review (Martin et al. 2008), 90% of patients given R-ESHAP received rituximab on day 1, 10% on day 5.

Chemotherapy

  • Rituximab (Rituxan) 375 mg/m2 IV once on day 1 (or day 5)
  • Etoposide (Vepesid) 40 mg/m2 IV over 1 hour once per day on days 1 to 4
  • Methylprednisolone (Solumedrol) 250 to 500 mg IV over 15 minutes once per day on days 1 to 5
    • In Martín et al. 2008, methylprednisolone could either be given on days 1 to 4 or days 1 to 5, with patients receiving total doses of anywhere from 1000 mg per cycle to 2500 mg per cycle
  • Cytarabine (Cytosar) 2000 mg/m2 IV over 2 hours once on day 5
  • Cisplatin (Platinol) 25 mg/m2/day IV continuous infusion over 96 hours (total dose per cycle: 100 mg/m2) on days 1 to 4

Supportive medications

21 to 28 day cycles ("after recovery of the toxic effects") x 6 to 8 cycles

References

  1. 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 verified protocol PubMed
  2. Retrospective: Martín A, Conde E, Arnan M, Canales MA, Deben G, Sancho JM, Andreu R, Salar A, García-Sanchez P, Vázquez L, Nistal S, Requena MJ, Donato EM, González JA, León A, Ruiz C, Grande C, González-Barca E, Caballero MD; Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL/TAMO Cooperative Group). R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study. Haematologica. 2008 Dec;93(12):1829-36. Epub 2008 Oct 22. link to original article contains verified protocol PubMed
  3. 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

R-GDP

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R-GDP: Rituximab, Gemcitabine, Dexamethasone, Platinol (Cisplatin)

Regimen

Study Evidence Comparator Efficacy
Crump et al. 2014 (NCIC-CTG LY.12) Phase III R-DHAP Noninferior RR

Chemotherapy

21-day cycle for up to 3 cycles

Responders proceeded to stem-cell mobilization and autologous stem cell transplant.

References

  1. Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains verified protocol PubMed

R-ICE

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R-ICE: Rituximab, Ifosfamide, Carboplatin, Etoposide

Regimen

Study Evidence Comparator Efficacy
Gisselbrecht et al. 2010 (CORAL) Phase III R-DHAP Seems not superior

Note: the paper refers to the non-randomized Kewalramani et al. 2004 regimen, although it has slightly different day numbering. Doses are the same.

Chemotherapy

Supportive medications

21-day cycle for 3 cycles

Patients with complete or partial response then received BEAM autologous stem-cell transplant.

References

  1. Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. link to original article contains verified protocol PubMed

Vinorelbine (Navelbine)

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Regimen

Study Evidence Comparator
Balzarotti et al. 1996 Non-randomized, <20 patients in this subgroup
Pettengell et al. 2012 Phase III, <20 in this arm Pixantrone

Chemotherapy

28-day cycles

References

  1. Balzarotti M, Santoro A, Tondini C, Fornier M, Bonadonna G. Activity of single agent vinorelbine in pretreated non-Hodgkin's lymphoma. Ann Oncol. 1996 Nov;7(9):970-2. link to original article contains verified protocol PubMed
  2. Review: Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82. Review. link to original article PubMed
  3. Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed

Relapsed/refractory, non-randomized or retrospective data

Blinatumomab (Blincyto)

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Regimen

Study Evidence
Viardot et al. 2016 Phase II

Two dosing schemas were evaluated; this is the preferred dosing regimen, per the authors.

Chemotherapy

  • Blinatumomab (Blincyto) as follows:
    • 9 µg/day IV continuous infusion during week 1, then
    • 28 µg/day IV continuous infusion during week 2, then
    • 112 µg/day IV continuous infusion for remainder of the 8-week course

Supportive medications

  • Dexamethasone (Decadron) 20 mg PO 6 to 12 hours before infusion start and dose increases, 20 mg PO 1 hour before infusion start and dose increases, and 8 mg PO TID for 2 days following infusion start and dose increases
    • Patients with neurologic symptoms or cytokine release syndrome received 8 mg PO/IV Q8H for up to 3 days, with a subsequent taper over 4 days

8-week course

Responders could receive a 4-week consolidation cycle after a 4-week treatment-free period. Patients relapsing within 2 years of treatment could receive another 8-week course.

References

  1. Viardot A, Goebeler ME, Hess G, Neumann S, Pfreundschuh M, Adrian N, Zettl F, Libicher M, Sayehli C, Stieglmaier J, Zhang A, Nagorsen D, Bargou RC. Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma. Blood. 2016 Mar 17;127(11):1410-6. Epub 2016 Jan 11. link to original article contains verified protocol PubMed

BR

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BR: Bendamustine, Rituximab

Regimen

Study Evidence
Ohmachi et al. 2013 Phase II
Vacirca et al. 2013 Phase II

Note: Bendamustine was given on days 2 & 3 by Ohmachi et al. and on days 1 & 2 by Vacirca et al.

Chemotherapy

Note: the bendamustine infusion instructions are for the Treanda formulation, which was discontinued on 3/31/2016.

Supportive medications

21-day cycle for up to 6 cycles

References

  1. Ohmachi K, Niitsu N, Uchida T, Kim SJ, Ando K, Takahashi N, Takahashi N, Uike N, Eom HS, Chae YS, Terauchi T, Tateishi U, Tatsumi M, Kim WS, Tobinai K, Suh C, Ogura M. Multicenter Phase II Study of Bendamustine Plus Rituximab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2013 Jun 10;31(17):2103-9. Epub 2013 May 6. link to original article contains verified protocol PubMed
  2. Vacirca JL, Acs PI, Tabbara IA, Rosen PJ, Lee P, Lynam E. Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma. Ann Hematol. 2014 Mar;93(3):403-9. Epub 2013 Aug 17. link to original article contains verified protocol PubMed

Brentuximab vedotin (Adcetris)

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Regimen

Study Evidence
Bartlett et al. 2014 Phase II
Jacobsen et al. 2015 Phase II

Bartlett et al. treated patients with undetectable CD30 by visual assessment using routine IHC. Jacobsen et al. treated patients with CD30+ non-Hodgkin lymphoma, as determined by IHC. 

====Chemotherapy====

21-day cycles, given until progression or unacceptable toxicity

References

  1. Abstract: Nancy L. Bartlett, MD, Mitchell R. Smith, MD, Ranjana Advani, MD, Tatyana Feldman, MD, Kerry J. Savage, MD MSc, Maria Corinna Palanca-Wessels, MD, PhD and Tanya Siddiqi, MD. Brentuximab Vedotin Monotherapy in DLBCL Patients with Undetectable CD30: Preliminary Results from a Phase 2 Study. ASH Annual Meeting 2014 Abstract 629 link to abstract
  2. Jacobsen ED, Sharman JP, Oki Y, Advani RH, Winter JN, Bello CM, Spitzer G, Palanca-Wessels MC, Kennedy DA, Levine P, Yang J, Bartlett NL. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015 Feb 26;125(9):1394-402. Epub 2015 Jan 8. link to original article contains verified protocol PubMed

EPOCH

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EPOCH: Etoposide, Prednisone, Oncovin, Cyclophosphamide, Hydroxydaunorubicin

Synonyms: CHEOP

Structured Concept: C63779 (NCI-T), C1880475 (NCI-MT/UMLS)

Regimen

Study Evidence
Wilson et al. 1993 Phase II

Chemotherapy

Supportive medications

21-day cycle for 6 to 8 cycles

References

  1. Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, Kohler DR, Jaffe ES, Herdt J, Cheson BD et al. 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 verified protocol PubMed

Everolimus (Afinitor)

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Regimen

Study Evidence
Witzig et al. 2011 Phase II

Chemotherapy

Supportive medications

  • "Patients could receive white blood cell growth factors, if neutropenia developed at physician's discretion. Erythropoietin treatment for anemia was permitted per standard guidelines."

28-day cycles, given until progression or unacceptable toxicity

References

  1. Witzig TE, Reeder CB, LaPlant BR, Gupta M, Johnston PB, Micallef IN, Porrata LF, Ansell SM, Colgan JP, Jacobsen ED, Ghobrial IM, Habermann TM. A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. Leukemia. 2011 Feb;25(2):341-7. Epub 2010 Dec 7. link to original article contains verified protocol PubMed

Everolimus & Rituximab

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Regimen

Study Evidence
Barnes et al. 2013 Phase II

Chemotherapy

  • Everolimus (Afinitor) 5 mg PO once per day on days 1 to 14, increased to 10 mg PO once per day for the remainder of cycle 1 and thereafter, if tolerated
  • Rituximab (Rituxan) 375 mg/m2 IV once per week x 4 weeks, then once on day 1 of cycle 2 onwards

28-day cycle for 6 cycles Responders had the option of continuing everolimus for another 6 months.

References

  1. Barnes JA, Jacobsen E, Feng Y, Freedman A, Hochberg EP, LaCasce AS, Armand P, Joyce R, Sohani AR, Rodig SJ, Neuberg D, Fisher DC, Abramson JS. Everolimus in combination with rituximab induces complete responses in heavily pretreated diffuse large B-cell lymphoma. Haematologica. 2013 Apr;98(4):615-9. Epub 2012 Nov 9. link to original article contains verified protocol PubMed

GVD

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GVD: Gemcitabine, Vinorelbine, Doxil (Doxorubicin liposomal)

Regimen

Study Evidence
Bai et al. 2013 Retrospective

Chemotherapy

14-day cycles

References

  1. Retrospective: Bai B, Huang HQ, Cai QQ, Wang XX, Cai QC, Lin ZX, Gao Y, Xia Y, Bu Q, Guo Y. Promising long-term outcome of gemcitabine, vinorelbine, liposomal doxorubicin (GVD) in 14-day schedule as salvage regimen for patients with previously heavily treated Hodgkin's lymphoma and aggressive non-Hodgkin's lymphoma. Med Oncol. 2013 Mar;30(1):350. Epub 2013 Jan 18. link to original article contains protocol PubMed

Ibritumomab tiuxetan (Zevalin)

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Regimen

To be completed

References

  1. Morschhauser F, Illidge T, Huglo D, Martinelli G, Paganelli G, Zinzani PL, Rule S, Liberati AM, Milpied N, Hess G, Stein H, Kalmus J, Marcus R. Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation. Blood. 2007 Jul 1;110(1):54-8. Epub 2007 Mar 26. link to original article PubMed

Ibrutinib (Imbruvica)

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Regimen

Study Evidence
Wilson et al. 2012 Phase II

Clinically meaningful responses were observed in the ABC subtype, only. Further clinical trials are currently underway.

Chemotherapy

Duration not specified

References

  1. Abstract: Wyndham H. Wilson, MD, PhD, John F. Gerecitano, MD, PhD, Andre Goy, MD, Sven de Vos, MD, PhD, Vaishalee P. Kenkre, MD, Paul M. Barr, MD, Kristie A. Blum, MD, Andrei R. Shustov, MD, Ranjana H. Advani, MD, Jason Lih, PhD, Mickey Williams, PhD, Roland Schmitz, PhD, Yandan Yang, PhD, Stefania Pittaluga, MD, PhD, George Wright, PhD, Lori A. Kunkel, MD, Jesse McGreivy, MD, Sriram Balasubramanian, PhD, Mei Cheng, PhD, Davina Moussa, Joseph J. Buggy, PhD and Louis M. Staudt, MD, PhD. The Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), Has Preferential Activity in the ABC Subtype of Relapsed/Refractory De Novo Diffuse Large B-Cell Lymphoma (DLBCL): Interim Results of a Multicenter, Open-Label, Phase 2 Study. Blood 120, a686 (2012). link to abstract

ICE

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ICE: Ifosfamide, Carboplatin, Etoposide

Regimen

Study Evidence
Zelenetz et al. 2003 Phase II

Third cycle intended to be followed by peripheral blood stem cell collection

Chemotherapy

14-day cycle for 3 cycles

Supportive medications

References

  1. 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 PubMed
  2. 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 verified protocol PubMed
  3. 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 PubMed

Lenalidomide (Revlimid)

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Regimen

Study Evidence
Wiernik et al. 2008 (NHL-002) Phase II
Witzig et al. 2011 (NHL-003) Phase II

Chemotherapy

28-day cycles until disease progression or unacceptable toxicity

References

  1. Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE, Lam W, McBride K, Wride K, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Habermann TM. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2008 Oct 20;26(30):4952-7. Epub 2008 Jul 7. link to original article contains verified protocol PubMed
  2. Witzig TE, Vose JM, Zinzani PL, Reeder CB, Buckstein R, Polikoff JA, Bouabdallah R, Haioun C, Tilly H, Guo P, Pietronigro D, Ervin-Haynes AL, Czuczman MS. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Ann Oncol. 2011 Jul;22(7):1622-7. Epub 2011 Jan 12. link to original article contains verified protocol PubMed

Lenalidomide & Rituximab

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Regimen #1

Study Evidence
Wang et al. 2013 Phase II

Chemotherapy

28-day cycles

Regimen #2

Study Evidence
Zinzani et al. 2011 Phase II

Chemotherapy

28-day cycle for 4 cycles

Patients with a response of stable disease or better proceeded to maintenance lenalidomide.

References

  1. Zinzani PL, Pellegrini C, Gandolfi L, Stefoni V, Quirini F, Derenzini E, Broccoli A, Argnani L, Pileri S, Baccarani M. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk. 2011 Dec;11(6):462-6. Epub 2011 May 4. link to original article contains verified protocol PubMed
    1. Update: Zinzani PL, Pellegrini C, Derenzini E, Argnani L, Pileri S. Long-term efficacy of the combination of lenalidomide and rituximab in elderly relapsed/refractory diffuse large B-cell lymphoma patients. Hematol Oncol. 2013 Dec;31(4):223-4. Epub 2013 Apr 26. link to original article PubMed
  2. Wang M, Fowler N, Wagner-Bartak N, Feng L, Romaguera J, Neelapu SS, Hagemeister F, Fanale M, Oki Y, Pro B, Shah J, Thomas S, Younes A, Hosing C, Zhang L, Newberry KJ, Desai M, Cheng N, Badillo M, Bejarano M, Chen Y, Young KH, Champlin R, Kwak L, Fayad L. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013 Sep;27(9):1902-9. Epub 2013 Apr 2. link to original article contains verified protocol PubMed

Mitoxantrone (Novantrone)

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Regimen

Study Evidence
Bajetta et al. 1988 Phase II

Chemotherapy

3-week cycles

References

  1. Bajetta E, Buzzoni R, Valagussa P, Bonadonna G. Mitoxantrone: an active agent in refractory non-Hodgkin's lymphomas. Am J Clin Oncol. 1988 Apr;11(2):100-3. contains protocol PubMed
  2. Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed

Obinutuzumab (Gazyva)

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Regimen

Study Evidence
Morschhauser et al. 2013 (GAUGUIN) Phase II

Chemotherapy

  • Obinutuzumab (Gazyva) as follows:
    • Cycle 1: 1600 mg (diluted to 10 mg/mL) IV once per day on days 1 & 8
    • Cycles 2 to 8: 800 mg IV once on day 1
    • Initial infusion rate is 50 mg/hour. In the absence of infusion-related reactions (IRRs), the rate is then increased by 50 mg/hour every 30 minutes, up to a maximum of 400 mg/hour.

Supportive medications

  • Acetaminophen (Tylenol) or paracetamol 650 to 1000 mg PO once 30 minutes prior to Obinutuzumab (Gazyva)
  • "An antihistamine" 30 minutes prior to Obinutuzumab (Gazyva); if there were no infusion-related reactions (IRRs) requiring medication or infusion interruption, antihistamine could be omitted for subsequent infusions
  • Premedication with corticosteroids recommended for patients at high risk of infusion-related reactions (IRRs)
  • Use of G-CSF allowed for severe neutropenia
  • Antibiotic prophylaxis allowed

21-day cycle for 8 cycles

References

  1. Morschhauser FA, Cartron G, Thieblemont C, Solal-Céligny P, Haioun C, Bouabdallah R, Feugier P, Bouabdallah K, Asikanius E, Lei G, Wenger M, Wassner-Fritsch E, Salles GA. Obinutuzumab (GA101) Monotherapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma or Mantle-Cell Lymphoma: Results From the Phase II GAUGUIN Study. J Clin Oncol. 2013 Aug 10;31(23):2912-9. Epub 2013 Jul 8. link to original article contains verified protocol PubMed

O-DHAP

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O-DHAP: Ofatumumab, Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study Evidence
Matasar et al. 2013 Phase II

Chemotherapy

Supportive medications

21-day cycle for 3 cycles

References

  1. Matasar MJ, Czuczman MS, Rodriguez MA, Fennessy M, Shea TC, Spitzer G, Lossos IS, Kharfan-Dabaja MA, Joyce R, Fayad L, Henkel K, Liao Q, Edvardsen K, Jewell RC, Fecteau D, Singh RP, Lisby S, Moskowitz CH. Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood. 2013 Jul 25;122(4):499-506. Epub 2013 May 21. link to original article contains verified protocol PubMed

O-ICE

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O-ICE: Ofatumumab, Ifosfamide, Carboplatin, Etoposide

Regimen

Study Evidence
Matasar et al. 2013 Phase II

Chemotherapy

Supportive medications

21-day cycle for 3 cycles

References

  1. Matasar MJ, Czuczman MS, Rodriguez MA, Fennessy M, Shea TC, Spitzer G, Lossos IS, Kharfan-Dabaja MA, Joyce R, Fayad L, Henkel K, Liao Q, Edvardsen K, Jewell RC, Fecteau D, Singh RP, Lisby S, Moskowitz CH. Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood. 2013 Jul 25;122(4):499-506. Epub 2013 May 21. link to original article contains verified protocol PubMed

Ofatumumab (Arzerra)

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Regimen

Study Evidence
Coiffier et al. 2013 (415 Study) Phase II

Chemotherapy

  • Ofatumumab (Arzerra) 300 mg IV on cycle 1 day 1, then 1000 mg IV once per week x 7 weeks (total of 8 doses)

Supportive medications

One course

References

  1. Coiffier B, Radford J, Bosly A, Martinelli G, Barca G, Davies A, Decaudin D, Gallop-Evans E, Padmanabhan-Iyer S, Van Eygen K, Wu KL, Gupta IV, Lin TS, Goldstein N, Jewell RC, Winter P, Lisby S; 415 study investigators. A multicentre, phase II trial of ofatumumab monotherapy in relapsed/progressive diffuse large B-cell lymphoma. Br J Haematol. 2013 Nov;163(3):334-42. Epub 2013 Aug 23. link to original article contains verified protocol PubMed

R-CVEP

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R-CVEP: Rituximab, Cyclophosphamide, Vorinostat, Etoposide, Prednisone

Regimen

Study Evidence
Straus et al. 2014 Phase II

The MTD for vorinostat was 300 mg in this phase I/II trial.

Chemotherapy

28-day cycle for 6 cycles

References

  1. Straus DJ, Hamlin PA, Matasar MJ, Lia Palomba M, Drullinsky PR, Zelenetz AD, Gerecitano JF, Noy A, Hamilton AM, Elstrom R, Wegner B, Wortman K, Cella D. Phase I/II trial of vorinostat with rituximab, cyclophosphamide, etoposide and prednisone as palliative treatment for elderly patients with relapsed or refractory diffuse large B-cell lymphoma not eligible for autologous stem cell transplantation. Br J Haematol. 2015 Mar;168(5):663-70. Epub 2014 Oct 15. link to original article contains protocol PubMed

R-DexaBEAM

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R-DexaBEAM: Rituximab, Dexamethasone, BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan

Regimen

Study Evidence
Kirschey et al. 2014 Phase II

Chemotherapy

3- to 4-week cycle for 2 cycles

Patient proceed to undergo high dose therapy and autologous stem cell transplant.

References

  1. Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. link to original article contains verified protocol PubMed

R-DHAP

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R-DHAP: Rituximab, Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study Evidence
Mey et al. 2006 Phase II

The doses here were used after a mid-protocol amendment pertaining to the first cycle.

First cycle

  • Rituximab (Rituxan) 375 mg/m2 IV once on day 1
  • Dexamethasone (Decadron) 40 mg PO once per day on days 3 to 5
  • Cytarabine (Cytosar) as follows:
    • Younger than 60 years: 1000 mg/m2 IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses)
    • Older than 60 years: 500 mg/m2 IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses)
  • Cisplatin (Platinol) 25 mg/m2/day IV continuous infusion on days 3 to 5 (total dose = 75 mg/m2)

3-week cycle

Subsequent cycles

  • Rituximab (Rituxan) 375 mg/m2 IV once on day 1
  • Dexamethasone (Decadron) 40 mg PO once per day on days 3 to 6
  • Cytarabine (Cytosar) as follows:
    • Younger than 60 years: 2000 mg/m2 IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses)
    • Older than 60 years: 1000 mg/m2 IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses)
  • Cisplatin (Platinol) 25 mg/m2/day IV continuous infusion on days 3 to 6 (total dose per cycle = 100 mg/m2)

3-week cycle up to 3 cycles (4 cycles, total)

Patients with complete or partial response were allowed to undergo autologous stem-cell transplant.

References

  1. Mey UJ, Orlopp KS, Flieger D, Strehl JW, Ho AD, Hensel M, Bopp C, Gorschlüter M, Wilhelm M, Birkmann J, Kaiser U, Neubauer A, Florschütz A, Rabe C, Hahn C, Glasmacher AG, Schmidt-Wolf IG. Dexamethasone, high-dose cytarabine, and cisplatin in combination with rituximab as salvage treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. Cancer Invest. 2006 Oct;24(6):593-600. link to original article contains verified protocol PubMed

R-EPOCH

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R-EPOCH: Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)

Regimen

Study Evidence
Jermann et al. 2004 Phase II

Note: this is not the dose-adjusted R-EPOCH regimen

Chemotherapy

21-day cycle for 4 to 6 cycles

References

  1. Jermann M, Jost LM, Taverna Ch, Jacky E, Honegger HP, Betticher DC, Egli F, Kroner T, Stahel RA. Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study. Ann Oncol. 2004 Mar;15(3):511-6. link to original article contains verified protocol PubMed

R-GDP

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R-GDP: Rituximab, Gemcitabine, Dexamethasone, Platinol (Cisplatin)

Regimen

Study Evidence
Hou et al. 2012 Non-randomized

Chemotherapy

21-day cycle for up to 6 cycles

References

  1. Hou Y, Wang HQ, Ba Y. Rituximab, gemcitabine, cisplatin, and dexamethasone in patients with refractory or relapsed aggressive B-cell lymphoma. Med Oncol. 2012 Dec;29(4):2409-16. Epub 2012 Apr 3. link to original article PubMed

R-GemOx

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R-GemOx: Rituximab, Gemcitabine, Oxaliplatin

Regimen #1 "GEMOX-R"

Study Evidence
López et al. 2008 Phase II

Chemotherapy

21-day cycle for 6 to 8 cycles

Regimen #2

Study Evidence
El Gnaoui et al. 2007 Phase II

Chemotherapy

Supportive medications

14-day cycle for up to 8 cycles

References

  1. El Gnaoui T, Dupuis J, Belhadj K, Jais JP, Rahmouni A, Copie-Bergman C, Gaillard I, Diviné M, Tabah-Fisch I, Reyes F, Haioun C. Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy. Ann Oncol. 2007 Aug;18(8):1363-8. Epub 2007 May 11. link to original article contains verified protocol PubMed
  2. López A, Gutiérrez A, Palacios A, Blancas I, Navarrete M, Morey M, Perelló A, Alarcón J, Martínez J, Rodríguez J. GEMOX-R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large-cell lymphoma: a phase II study. Eur J Haematol. 2008 Feb;80(2):127-32. Epub 2007 Nov 20. link to original article contains verified protocol PubMed
  3. Mounier N, El-Gnaoui T, Tilly H, Canioni D, Sebban C, Casasnovas RO, Delarue R, Sonet A, Beaussart P, Petrella T, Castaigne S, Bologna S, Salles G, Rahmouni A, Gaulard P, Haioun C. Rituximab plus gemcitabine and oxaliplatin in refractory/relapsed patients with diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial. Haematologica. 2013 Nov;98(11):1726-31. Epub 2013 Jun 10. link to original article contains verified protocol PubMed

R-ICE

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R-ICE: Rituximab, Ifosfamide, Carboplatin, Etoposide

Regimen #1

Study Evidence
Guo et al. 2014 Phase II

Chemotherapy

3 cycles; duration of cycles not specified in the abstract

Regimen #2

Study Evidence
Zelenetz et al. 2003 Phase II
Kewalramani et al. 2004 Phase II

Third cycle intended to be followed by peripheral blood stem cell collection

Chemotherapy

14-day cycle for 3 cycles

Supportive medications

References

  1. 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 verified protocol PubMed
  2. Kewalramani T, Zelenetz AD, Nimer SD, Portlock C, Straus D, Noy A, O'Connor O, Filippa DA, Teruya-Feldstein J, Gencarelli A, Qin J, Waxman A, Yahalom J, Moskowitz CH. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2004 May 15;103(10):3684-8. Epub 2004 Jan 22. link to original article contains regimen PubMed
  3. Guo Y, Chen Y, Hong X, Yu L, Ma J, Shi Y, Liu T, Jiang W, Zhu J, Jin J, Zou P, Wu D, Shen Z. [A phase II multicenter study to investigate R-ICE as a salvage therapy for relapsed diffuse large B-cell lymphoma]. Zhonghua Xue Ye Xue Za Zhi. 2014 Apr;35(4):314-7. Chinese. link to original article PubMed

RICER

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RICER: Rituximab, Ifosfamide, Carboplatin, Etoposide, Revlimid (Lenalidomide)

Regimen

Study Evidence
Feldman et al. 2014 Phase II

Chemotherapy

Supportive medications

14-day cycle for 2 cycles

Responders received a 3rd cycle with stem cell collection 10 to 14 days afterwards, followed by autologous stem cell transplant.

References

  1. Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014 Jul;166(1):77-83. Epub 2014 Mar 25. link to original article contains verified protocol PubMed

R-IFE

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R-IFE: Rituximab, IFosfamide, Etoposide

Regimen

Study Evidence
Pardal et al. 2014 Phase II

Treatment preceded by R-MegaCHOP x3; these were patients with PET-positive disease at interim assessment.

Chemotherapy

Supportive medications

2 cycles (duration not specified)

Responders proceeded to undergo autologous stem cell transplant.

References

  1. Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. link to original article contains verified protocol PubMed

R-NIMP

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R-NIMP: Rituximab, Navelbine (Vinorelbine), Ifosfamide, Mitoxantrone, Prednisone

Regimen

Study Evidence
Gyan et al. 2013 Phase II

BSA was capped at 2 for all dose calculations.

Chemotherapy

Supportive medications

28-day cycle for 3 cycles

Responders were recommended to undergo 3 additional cycles or autologous stem cell transplant.

References

  1. Gyan E, Damotte D, Courby S, Sénécal D, Quittet P, Schmidt-Tanguy A, Banos A, Le Gouill S, Lamy T, Fontan J, Maisonneuve H, Alexis M, Dreyfus F, Tournilhac O, Laribi K, Solal-Céligny P, Arakelyan N, Cartron G, Gressin R; GOELAMS Group. High response rate and acceptable toxicity of a combination of rituximab, vinorelbine, ifosfamide, mitoxantrone and prednisone for the treatment of diffuse large B-cell lymphoma in first relapse: results of the R-NIMP GOELAMS study. Br J Haematol. 2013 Jul;162(2):240-9. Epub 2013 May 21. link to original article contains verified protocol PubMed

Temsirolimus (Torisel)

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Regimen

Study Evidence
Smith et al. 2010 Phase II

Chemotherapy

28-day cycle for up to 6 cycles

References

  1. Smith SM, van Besien K, Karrison T, Dancey J, McLaughlin P, Younes A, Smith S, Stiff P, Lester E, Modi S, Doyle LA, Vokes EE, Pro B. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol. 2010 Nov 1;28(31):4740-6. Epub 2010 Sep 13. link to original article contains verified protocol PubMed

TTR

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TTR: Taxol (Paclitaxel), Topotecan, Rituximab

Regimen

Study Evidence
Westin et al. 2014 Phase II

Chemotherapy

Supportive medications

21-day cycle up to a maximum of 6 cycles

References

  1. Westin JR, McLaughlin P, Romaguera J, Hagemeister FB, Pro B, Dang NH, Samaniego F, Rodriguez MA, Fayad L, Oki Y, Fanale M, Fowler N, Nastoupil L, Feng L, Loyer E, Younes A. Paclitaxel, topotecan and rituximab: long term outcomes of an effective salvage programme for relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2014 Oct;167(2):177-84. Epub 2014 Jul 8. link to original article contains verified protocol PubMed

Consolidation and/or maintenance after salvage therapy

Autologous stem cell transplant

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Regimen #1

Study Evidence Comparator Efficacy
Philip et al. 1995 (PARMA) Phase III DHAP x4 Increased OS

Treatment preceded by DHAP x 2. Radiation was also given to sites of bulky disease (>5cm); see paper for details.

  • BEAC followed by autologous stem cell transplant

Follow the link for details.

Regimen #2

Study Evidence
Gisselbrecht et al. 2010 (CORAL) Non-randomized
Pardal et al. 2014 Phase II

Treatment in CORAL preceded by R-ICE x 3 versus R-DHAP x 3. Treatment in Pardal et al. 2014 preceded by R-MegaCHOP x3 and R-IFE x 2.

  • BEAM followed by autologous stem cell transplant

Follow the link for details. In CORAL, treatment was followed by maintenance rituximab versus observation.

Regimen #3

Study Evidence
Feldman et al. 2014 Phase II

Treatment preceded by RICER x 3.

  • BEAM followed by autologous stem cell transplant

Follow the link for details. If patients were fully recovered within 90 days, they proceeded to lenalidomide maintenance.

Regimen #4

Study Evidence
Kirschey et al. 2014 Phase II

Treatment preceded by R-DexaBEAM x 2.

References

  1. Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. 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 PubMed
  2. Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. link to original article contains verified protocol PubMed
  3. Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014 Jul;166(1):77-83. Epub 2014 Mar 25. link to original article contains verified protocol PubMed
  4. Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. link to original article contains verified protocol PubMed
  5. Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains verified protocol PubMed
  6. Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. link to original article contains verified protocol PubMed

Lenalidomide (Revlimid)

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Regimen #1

Study Evidence
Feldman et al. 2014 Phase II

Treatment preceded by BEAM autologous transplant.

Chemotherapy

28-day cycles for up to 12 months

Regimen #2

Study Evidence
Zinzani et al. 2011 Phase II

Treatment preceded by lenalidomide & rituximab x 4.

Chemotherapy

28-day cycle for 8 months

References

  1. Zinzani PL, Pellegrini C, Gandolfi L, Stefoni V, Quirini F, Derenzini E, Broccoli A, Argnani L, Pileri S, Baccarani M. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk. 2011 Dec;11(6):462-6. Epub 2011 May 4. link to original article contains verified protocol PubMed
    1. Update: Zinzani PL, Pellegrini C, Derenzini E, Argnani L, Pileri S. Long-term efficacy of the combination of lenalidomide and rituximab in elderly relapsed/refractory diffuse large B-cell lymphoma patients. Hematol Oncol. 2013 Dec;31(4):223-4. Epub 2013 Apr 26. link to original article PubMed
  2. Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014 Jul;166(1):77-83. Epub 2014 Mar 25. link to original article contains verified protocol PubMed

Observation

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Regimen

Study Evidence Comparator Efficacy
Gisselbrecht et al. 2012 (CORAL) Phase III Rituximab Seems not superior

No further treatment after BEAM autologous stem cell transplant.

References

  1. Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Dührsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Brière J, Salles G, Moskowitz CH, Glass B. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012 Dec 20;30(36):4462-9. Epub 2012 Oct 22. link to original article contains verified protocol PubMed

Rituximab (Rituxan)

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Regimen

Study Evidence Comparator Efficacy
Gisselbrecht et al. 2012 (CORAL) Phase III Observation Seems not superior

Treatment preceded by BEAM autologous stem cell transplant, and begins on day +28.

Chemotherapy

1 year course

References

  1. Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Dührsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Brière J, Salles G, Moskowitz CH, Glass B. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012 Dec 20;30(36):4462-9. Epub 2012 Oct 22. link to original article contains verified protocol PubMed

Response criteria

NCI Sponsored International Working Group Criteria (1999)

  1. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. link to original article PubMed

International Harmonization Project on Lymphoma revised criteria (2007)

  1. Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. Epub 2007 Jan 22. link to original article PubMed

Prognosis

IPI and age-adjusted IPI (1993)

To be completed

  1. A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med. 1993 Sep 30;329(14):987-94. link to original article PubMed

Investigational agents

These are drugs under study with at least some promising results for this disease.

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