Difference between revisions of "Aggressive Non-Hodgkin lymphoma"

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'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]].'''
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='''Aggressive B-cell non-Hodgkin lymphoma regimens have been moved to their histology-specific subtype pages. Please use the links below and/or update your bookmarks.'''=
  
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Is there a regimen missing from this list?  Would you like to share a different dosage/schedule or an additional reference for a regimen?  Have you noticed an error?  Do you have an idea that will help the site grow to better meet your needs and the needs of many others?  You are [[How_to_contribute|invited to contribute to the site]].
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==[[Diffuse large B-cell lymphoma|Diffuse large B-cell lymphoma (DLBCL)]]==
  
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{{TOC limit|limit=3}}
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==[[Burkitt lymphoma|Burkitt lymphoma (BL) or Burkitt-like lymphoma]]==
  
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=DLBCL, untreated=
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==[[Mediastinal gray-zone lymphoma|Mediastinal gray-zone lymphoma (MGZL)]]==
  
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==ACVBP-R==
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==[[Primary mediastinal B-cell lymphoma|Primary mediastinal B-cell lymphoma (PMBL)]]==
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ACVBP-R: '''<u>A</u>'''driamycin, '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''indesine, '''<u>B</u>'''leomycin, '''<u>P</u>'''rednisone, '''<u>R</u>'''ituximab
 
  
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Synonyms: R-ACVBP
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==[[Transformed lymphoma|Transformed lymphoma (TL)]]==
  
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Structured Concept: none
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[[Category:Obsolete pages]]
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Level of Evidence:
 
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<span
 
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style="background:#00CD00;
 
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padding:3px 6px 3px 6px;
 
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border-color:black;
 
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border-width:2px;
 
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border-style:solid;">Phase III</span>
 
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<span title=="3-year OS 92% (ACVBP-R) vs. 84% (R-CHOP)"
 
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style="background:#00CD00;
 
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padding:3px 6px 3px 6px;
 
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border-color:black;
 
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border-width:2px;
 
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border-style:solid;">Improved OS</span>
 
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<span
 
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style="background:#ff0000;
 
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padding:3px 6px 3px 6px;
 
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border-color:black;
 
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border-width:2px;
 
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border-style:solid;">Increased toxicity</span>
 
−
 
 
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===Induction Regimen===
 
−
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m2 IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 75 mg/m2 IV once on day 1
 
−
*[[Vindesine (Eldisine)]] 2 mg/m2 IV once on days 1 & 5
 
−
*[[Bleomycin (Blenoxane)]] 10 units IV once on days 1 & 5
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO once per day on days1 to 5
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
*[[Methotrexate (MTX)]] 15 mg intrathecal on day 1 for CNS prophylaxis
 
−
 
 
−
'''14-day cycles x 4 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 6 to 13
 
−
 
 
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===Consolidation Regimen===
 
−
*[[Methotrexate (MTX)]] 3000 mg/m2 IV once on day 1
 
−
 
 
−
Supportive medications:
 
−
*[[Folinic acid (Leucovorin)|Calcium folinate - Folinic acid (Leucovorin)]] rescue
 
−
 
 
−
'''14-day cycles x 2 cycles''', beginning 4 weeks after completion of induction, then
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
*[[Etoposide (Vepesid)]] 300 mg/m2 IV once on day 1
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m2 IV once on day 1
 
−
 
 
−
'''14-day cycles x 4 cycles''', beginning 2 weeks after completion of MTX, then
 
−
 
 
−
*[[Cytarabine (Cytosar)]] 100 mg/m2 SC once per day on days1 to 4
 
−
 
 
−
'''14-day cycles x 2 cycles''', beginning 2 weeks after completion of REI
 
−
 
 
−
===References===
 
−
# 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. [http://www.sciencedirect.com/science/article/pii/S0140673611610404 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
 
−
 
 
−
==CDOP==
 
−
CDOP: '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''oxil, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once over 30 minutes on day 1
 
−
*[[Doxorubicin liposomal (Doxil)]] 30 mg/m2 IV once over 1 hour on day 1
 
−
*[[Vincristine (Oncovin)]] 2 IV once over 15 minutes on day 1
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO once per day on days 1 to 5
 
−
 
 
−
'''21-day cycles x 6 to 8 cycles'''
 
−
 
 
−
===References===
 
−
# Martino R, Perea G, Caballero MD, Mateos MV, Ribera JM, de Oteyza JP, Arranz R, Terol MJ, Sierra J, San Miguel JF. Cyclophosphamide, pegylated liposomal doxorubicin (Caelyx), vincristine and prednisone (CCOP) in elderly patients with diffuse large B-cell lymphoma: results from a prospective phase II study. Haematologica. 2002 Aug;87(8):822-7. [http://www.haematologica.org/content/87/8/822.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12161358 PubMed]
 
−
 
 
−
==CHOP==
 
−
CHOP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
 
−
 
 
−
Synonyms: CHOP-21, ACOP, CAVP, COPA, VACP, VCAP
 
−
 
 
−
Structured Concept: [http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary==NCI%20Thesaurus&version==12.09d&code==C9549&key==1801231401&b==1&n==null C9549] (NCI-T), [http://ncim.nci.nih.gov/ncimbrowser/ConceptReport.jsp?dictionary==NCI%20MetaThesaurus&code==C0055598 C0055598] (NCI-MT/UMLS)
 
−
 
 
−
===Regimen #1, Elias et al. 1978; Jones et al. 1979; Fisher et al. 1993; Miller et al. 1998===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once over 15 minutes on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV bolus over 1 to 2 minutes on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV bolus over 1 to 2 minutes on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days1 to 5
 
−
 
 
−
'''21-day cycles x 8 cycles'''
 
−
 
 
−
===Regimen #2, Pfreundschuh et al. 2004 (NHL-B1) & Verdonck et al. 2007===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days1 to 5
 
−
 
 
−
'''21-day cycles x 6 cycles'''
 
−
 
 
−
Supportive medications (only listed in Pfreundschuh et al. 2004):
 
−
*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
 
−
 
 
−
===Regimen #3, Miller et al. 1998 - CHOP-21 & radiation===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once over 15 minutes on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV bolus over 1 to 2 minutes on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV bolus over 1 to 2 minutes on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days1 to 5
 
−
 
 
−
'''21-day cycles x 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, Coiffier et al. 2002 (LNH-98.5)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[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 days1 to 5
 
−
 
 
−
'''21-day cycles x 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
 
−
 
 
−
===Regimen #5, Habermann et al. 2006 (CALGB 9793)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[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 per cycle: 2 mg) IV once on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg/m2 PO once per day on days 1 to 5
 
−
 
 
−
'''21-day cycles x 6 to 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] "recommended according to guidelines"
 
−
 
 
−
===Regimen #6, Pfreundschuh et al. 2004 (NHL-B2)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
====Pre-phase treatment====
 
−
''Recommended "to improve the performance status of patients and to ameliorate side-effects of the first chemotherapy cycle."''
 
−
*[[Vincristine (Oncovin)]] 1 mg IV once (day not specified)
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 7
 
−
 
 
−
'''7-day course''', then proceed to main regimen
 
−
 
 
−
====Main CHOP regimen====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
 
 
−
'''21-day cycles x 6 cycles'''
 
−
 
 
−
Supportive medications
 
−
*[[Filgrastim (Neupogen)]] "at the treating physician's discretion"
 
−
 
 
−
====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===
 
−
# 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. '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/361209 PubMed]
 
−
# Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Butler JJ, Byrne GE Jr, Moon TE, Fisher R, Haskins CL, Coltman CA Jr. Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study. Cancer. 1979 Feb;43(2):417-25. '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/84706 PubMed]
 
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJM199304083281404 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/7680764 PubMed]
 
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJM199807023390104 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9647875 PubMed]
 
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa011795 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11807147 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, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. [http://bloodjournal.hematologylibrary.org/content/104/3/634.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15016643 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]
 
−
# 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]
 
−
# 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. [http://jco.ascopubs.org/content/24/19/3121.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16754935 PubMed]
 
−
# 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. [http://jco.ascopubs.org/content/25/7/787.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17228021 PubMed]
 
−
# Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, Ossenkoppele GJ, Doorduijn JK, Sonneveld P, van Imhoff GW. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007 Apr 1;109(7):2759-66. [http://bloodjournal.hematologylibrary.org/content/109/7/2759.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17132720 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:''' 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/22118442 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]
 
−
 
 
−
==CHOP Intensified==
 
−
CHOP-DI: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone, '''<u>D</u>'''ose '''<u>I</u>'''ntense
 
−
<br>I-CHOP:  '''<u>I</u>'''ntensified '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
 
−
 
 
−
Synonyms: CHOP-14, CHOP-DI, I-CHOP
 
−
 
 
−
Structured Concept: none
 
−
 
 
−
===Regimen #1, Blayney et al. 2003 - CHOP-DI, SWOG 9349===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Cyclophosphamide (Cytoxan)]] 1600 mg/m2 IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 65 mg/m2 IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 IV once on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days1 to 5
 
−
 
 
−
'''14-day cycles x up to 6 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 2 to 11, or until ANC is greater than 10,000
 
−
 
 
−
===Regimen #2, Verdonck et al. 2007 (I-CHOP)===
 
−
 
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
<span title=="6-year OS 50% (CHOP-21) vs. 61% (I-CHOP), p==NS"
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Equivalent OS</span>
 
−
<span
 
−
style="background:#ff0000;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Increased toxicity</span>
 
−
 
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m2 IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 70 mg/m2 IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days1 to 5
 
−
 
 
−
'''14-day cycles x 6 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 2 to 11
 
−
 
 
−
===Regimen #3, Pfreundschuh et al. 2004 (NHL-B2, CHOP-14) & Pfreundschuh et al. 2008 (RICOVER-60)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
====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.''
 
−
*[[Vincristine (Oncovin)]] 1 mg IV once (day not specified)
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 7
 
−
 
 
−
'''7-day course''', then proceed to main CHOP-14 regimen
 
−
 
 
−
====Main CHOP-14 regimen====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
 
 
−
'''14-day cycles x 6 cycles'''; some patients in Pfreundschuh et al. 2008 received 14-day cycles x 8 cycles
 
−
 
 
−
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
 
−
 
 
−
====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===
 
−
# 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. [http://jco.ascopubs.org/content/21/13/2466.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12829664 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, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. [http://bloodjournal.hematologylibrary.org/content/104/3/634.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15016643 PubMed]
 
−
# Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, Ossenkoppele GJ, Doorduijn JK, Sonneveld P, van Imhoff GW. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007 Apr 1;109(7):2759-66. [http://bloodjournal.hematologylibrary.org/content/109/7/2759.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17132720 PubMed]
 
−
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18226581 PubMed]
 
−
 
 
−
==CHOP Modified==
 
−
CHOP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
''This regimen is designed for elderly patients and is of lower intensity than standard CHOP.''
 
−
 
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m2 IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 30 mg/m2 IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1 mg IV once on day 1
 
−
*[[Prednisolone (Millipred)]] 20 mg PO BID on days 1 to 5
 
−
 
 
−
'''21-day cycles x 6 cycles'''
 
−
 
 
−
===References===
 
−
# 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. [http://annonc.oxfordjournals.org/content/14/2/258.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12562653 PubMed]
 
−
 
 
−
==CHOPE, CHOEP==
 
−
CHOPE: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone, '''<u>E</u>'''toposide<br>
 
−
CHOEP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone
 
−
 
 
−
Synonyms: CHOEP, VAC0P
 
−
 
 
−
Structured Concept: [http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary==NCI%20Thesaurus&version==12.09d&code==C9702&key==1863263010&b==1&n==null C9702] (NCI-T), [http://ncim.nci.nih.gov/ncimbrowser/ConceptReport.jsp?dictionary==NCI%20MetaThesaurus&code==C0212922 C0212922](NCI-MT/UMLS)
 
−
 
 
−
===Example orders===
 
−
*[[Example orders for CHOEP in lymphoma]]
 
−
 
 
−
===Regimen, Pfreundschuh et al. 2004 (NHL-B2)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days1 to 5
 
−
*[[Etoposide (Vepesid)]] 100 mg/m2 IV once per day on days 1 to 3
 
−
*Patients with initial bulky disease (mass conglomerate at least 7.5 cm) received 36 Gy radiation therapy and to extranodal sites of disease when possible
 
−
 
 
−
'''14 or 21-day cycles x 6 cycles''', next cycle to start as long as WBC is >2.5 and platelets >80
 
−
*CHOEP-14 uses 14-day cycles; CHOEP-21 uses 21-day cycles
 
−
 
 
−
Supportive medications:
 
−
*For 14-day cycles: [[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)]] use for 21-day cycles is by discretion of ordering physician
 
−
 
 
−
===References===
 
−
# 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, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. [http://bloodjournal.hematologylibrary.org/content/104/3/634.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15016643 PubMed]
 
−
 
 
−
==CNOP, MCOP==
 
−
CNOP: '''<u>C</u>'''yclophosphamide, '''<u>N</u>'''ovantrone, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
 
−
MCOP: '''<u>M</u>'''itoxantrone, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m2 IV once on day 1
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1 mg IV once on day 1
 
−
*[[Prednisolone (Millipred)]] 20 mg PO BID on days 1 to 5
 
−
 
 
−
'''21-day cycles x 6 cycles'''
 
−
 
 
−
===References===
 
−
# 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. [http://annonc.oxfordjournals.org/content/14/2/258.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12562653 PubMed]
 
−
 
 
−
==DA-EPOCH==
 
−
DA-EPOCH: '''<u>D</u>'''ose '''<u>A</u>'''djusted '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin
 
−
 
 
−
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)
 
−
 
 
−
===Regimen, Wilson et al. 2002 - dose-adjusted EPOCH (DA-EPOCH)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Etoposide (Vepesid)]] 50 mg/m2/day (total dose of 200 mg/m2) IV continuous infusion on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO BID on days 1 to 5
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/m2/day (total dose of 1.6 mg/m2) IV continuous infusion on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m2/day (total dose of 40 mg/m2) IV continuous infusion on days 1 to 4
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once over 15 minutes on day 5
 
−
 
 
−
Supportive medications:
 
−
*[[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:
 
−
**[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO BID 3 days per week
 
−
**[[Atovaquone (Mepron)]] 1500 mg PO once per day
 
−
**Pentamidine (Nebupent) 300 mg nebulized every 28 days
 
−
 
 
−
'''21-day cycles x 6 to 8 cycles'''
 
−
 
 
−
Dose-adjustments for EPOCH protocol:
 
−
*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===
 
−
# Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, Steinberg SM, Little RF, Janik J, Gutierrez M, Raffeld M, Staudt L, Cheson BD, Longo DL, Harris N, Jaffe ES, Chabner BA, Wittes R, Balis F. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15;99(8):2685-93. [http://bloodjournal.hematologylibrary.org/content/99/8/2685.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11929754 PubMed]
 
−
 
 
−
==DA-R-EPOCH==
 
−
DA-R-EPOCH: '''<u>D</u>'''ose '''<u>A</u>'''djusted '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin
 
−
 
 
−
Synonyms: DA-EPOCH-R, EPOCH-R, REPOCH
 
−
 
 
−
Structured Concept: [http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary==NCI%20Thesaurus&version==12.09d&code==C63461 C63461] (NCI-T), [http://ncim.nci.nih.gov/ncimbrowser/ConceptReport.jsp?dictionary==NCI%20MetaThesaurus&code==C1882521 C1882521] (NCI-MT/UMLS)
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per cycle or day 1 before the start of EPOCH (depending on reference)
 
−
*[[Etoposide (Vepesid)]] 50 mg/m2/day (total dose of 200 mg/m2) IV continuous infusion on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO BID on days 1 to 5
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/m2/day (total dose of 1.6 mg/m2) IV continuous infusion on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m2/day (total dose of 40 mg/m2) IV continuous infusion on days 1 to 4
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once over 15 minutes on day 5
 
−
 
 
−
'''21-day cycles x 6 to 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[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:
 
−
**[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO BID 3 days per week
 
−
***Alternative used only in García-Suárez et al. 2007: cotrimoxazole 480 mg PO BID 3 days per week
 
−
**[[Atovaquone (Mepron)]] 1500 mg PO once per day
 
−
**Pentamidine (Nebupent) 300 mg nebulized every 28 days
 
−
*Only in García-Suárez et al. 2007: [[Darbepoetin alfa (Aranesp)]] 2.25 ug/kg SC when hemoglobin concentration was ≤100 g/l.
 
−
 
 
−
Dose-adjustments for EPOCH protocol:
 
−
*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.
 
−
 
 
−
'''21-day cycles x 6 to 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*EITHER [[Filgrastim (Neupogen)]] 5 mcg/kg SQ once per day, starting 24 hours after EPOCH is completed and continuing until "neutrophil recovery"--no absolute count specified
 
−
*OR [[Pegfilgrastim (Neulasta)]] 6 mg SC x1 24 hours after EPOCH is completed
 
−
*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO 3x per week (e.g. Monday, Wednesday, Friday)
 
−
*Fluconazole (Diflucan) 100 mg PO once per day
 
−
*Ciprofloxacin (Cipro) 500 mg PO BID, starting on day 8 and to continue to at least day 15 or postnadir ANC of at least 1000
 
−
**Other fluoroquinolone can be used at discretion of physician
 
−
 
 
−
===References===
 
−
# 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. [http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2006.06438.x/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17233819 PubMed]
 
−
# 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. [http://jco.ascopubs.org/content/26/16/2717.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/18378569 PubMed]
 
−
# 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. [http://www.haematologica.org/content/97/5/758.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/22133772 PubMed]
 
−
 
 
−
==MACOP-B==
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
To be completed
 
−
 
 
−
===References===
 
−
# Klimo P, Connors JM. MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med. 1985 May;102(5):596-602. [http://annals.org/article.aspx?articleid=699617 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/2580468 PubMed]
 
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJM199304083281404 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/7680764 PubMed]
 
−
 
 
−
 
 
−
==m-BACOD==
 
−
m-BACOD: '''<u>m</u>'''ethotrexate (moderate dose), '''<u>B</u>'''leomycin, '''<u>A</u>'''driamycin (doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (vincristine), '''<u>D</u>'''examethasone
 
−
 
 
−
Structured Concept: [http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary==NCI%20Thesaurus&version==12.09d&code==C63458 C63458] (NCI-T), [http://ncim.nci.nih.gov/ncimbrowser/ConceptReport.jsp?dictionary==NCI%20MetaThesaurus&code==C1883662 C1883662] (NCI-MT/UMLS)
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Methotrexate (MTX)]] 200 mg/m2 IV once on days 8 & 15
 
−
*[[Folinic acid (Leucovorin)]] 10 mg/m2 PO/IV Q6H x 8 doses, starting 24 hours after methotrexate
 
−
*[[Bleomycin (Blenoxane)]] 4 units/m2 IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 45 mg/m2 IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m2 IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
 
−
*[[Dexamethasone (Decadron)]] 6 mg/m2 (no route specified) once per day on days 1 to 5
 
−
 
 
−
Dose adjustments:
 
−
*If nadir WBC <1,000 or nadir platelets <50,000: 50% of cyclophosphamide and doxorubicin
 
−
*If WBC <1,000, platelets <50,000, or creatinine >50% of baseline on day of treatment, methotrexate was omitted
 
−
 
 
−
'''21-day cycles x 10 cycles'''
 
−
 
 
−
Supportive medications: none reported
 
−
 
 
−
===References===
 
−
# Shipp MA, Yeap BY, Harrington DP, Klatt MM, Pinkus GS, Jochelson MS, Rosenthal DS, Skarin AT, Canellos GP. The m-BACOD combination chemotherapy regimen in large-cell lymphoma: analysis of the completed trial and comparison with the M-BACOD regimen. J Clin Oncol. 1990 Jan;8(1):84-93. [http://jco.ascopubs.org/content/8/1/84.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/1688615 PubMed]
 
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJM199304083281404 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/7680764 PubMed]
 
−
 
 
−
==ProMACE-CytaBOM==
 
−
ProMACE-CytaBOM: '''<u>Pro</u>'''lix (prednisone), '''<u>M</u>'''ethotrexate, '''<u>A</u>'''driamycin (doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>Cyta</u>'''rabine, '''<u>B</u>'''leomycin, '''<u>O</u>'''ncovin (vincristine), '''<u>M</u>'''ethotrexate
 
−
 
 
−
Structured Concept: [http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary==NCI%20Thesaurus&version==12.09d&code==C63460 C63460] (NCI-T), [http://ncim.nci.nih.gov/ncimbrowser/ConceptReport.jsp?dictionary==NCI%20MetaThesaurus&code==C1882461 C1882461] (NCI-MT/UMLS)
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Cyclophosphamide (Cytoxan)]] 650 mg/m2 IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m2 IV once on day 1
 
−
*[[Etoposide (Vepesid)]] 120 mg/m2 IV once on day 1
 
−
*[[Cytarabine (Cytosar)]] 300 mg/m2 IV once on day 8
 
−
*[[Bleomycin (Blenoxane)]] 5 units/m2 IV once on day 8
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 IV once on day 8
 
−
*[[Methotrexate (MTX)]] 120 mg/m2 IV once on day 8
 
−
*[[Folinic acid (Leucovorin)]] 25 mg/m2 PO Q6H x 4 doses, starting 24 hours after methotrexate
 
−
*[[Prednisone (Sterapred)|Prednisone (Prolix)]] 60 mg/m2 PO once per day on days 1 to 14
 
−
*Patients with initial bone or bone marrow involvement who achieved a CR were treated with 2,400 cGy prophylactic cranial irradiation.
 
−
 
 
−
Dose adjustments:
 
−
*"If WBC is ≥4,000, use 100% doses of all drugs
 
−
*If WBC count is 3,000 to 3,999, 100% prednisone, bleomycin, vincristine, cytarabine, and methotrexate; 75% cyclophosphamide, Adriamycin, and etoposide
 
−
*If WBC count is 2,000 to 2,999, 100% prednisone, bleomycin, vincristine, and methotrexate; 75% etoposide, cytarabine; 50% cyclophosphamide, Adriamycin
 
−
*If WBC count is 1,000 to 1,999, 100% prednisone, bleomycin, vincristine and methotrexate; 25% cyclophosphamide, Adriamycin, etoposide, and cytarabine
 
−
*If WBC count is 0 to 999, 100% prednisone, vincristine, and bleomycin; 50% methotrexate, no other drugs
 
−
*If platelet count is ≥100,000, use 100% doses of all drugs
 
−
*If platelet count is 50,000 to 99,000, 100% prednisone, bleomycin, vincristine, and methotrexate; 50% etoposide and cytarabine; 25% cyclophosphamide and Adriamycin
 
−
*If platelet count is 0 to 49,000, 100% prednisone, bleomycin, and vincristine; 50% methotrexate, no other drugs"
 
−
 
 
−
'''21-day cycles x 6 cycles or 2 cycles after maximum clinical response'''
 
−
 
 
−
Supportive medications:
 
−
*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO BID throughout the course of treatment
 
−
 
 
−
===References===
 
−
# Longo DL, DeVita VT Jr, Duffey PL, Wesley MN, Ihde DC, Hubbard SM, Gilliom M, Jaffe ES, Cossman J, Fisher RI et al. Superiority of ProMACE-CytaBOM over ProMACE-MOPP in the treatment of advanced diffuse aggressive lymphoma: results of a prospective randomized trial. J Clin Oncol. 1991 Jan;9(1):25-38. Erratum in: J Clin Oncol 1991 Apr;9(4):710. [http://jco.ascopubs.org/content/9/1/25.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/1702144 PubMed]
 
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJM199304083281404 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/7680764 PubMed]
 
−
 
 
−
==R-CDOP==
 
−
R-CDOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''oxil, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
''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.''
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
 
−
*[[Doxorubicin liposomal (Doxil)]] 30 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 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
 
−
 
 
−
'''21-day cycles x 6 cycles'''
 
−
 
 
−
===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]
 
−
 
 
−
==R-CEOP==
 
−
R-CEOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#ff0000;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Retrospective</span>
 
−
 
 
−
''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.''
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 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
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (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
 
−
**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
 
−
 
 
−
'''21-day cycles x 3 to 4 cycles +/- radiation therapy for patients with limited stage disease; 6 cycles for patients with advanced stage disease'''
 
−
 
 
−
===References===
 
−
# 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 [http://abstracts.hematologylibrary.org/cgi/content/abstract/114/22/408?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=moccia&searchid=1&FIRSTINDEX=0&volume=114&issue=22&resourcetype=HWCIT link to abstract]
 
−
 
 
−
==R-CHOEP-14==
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
To be completed
 
−
 
 
−
===References===
 
−
# 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. [http://www.ncbi.nlm.nih.gov/pubmed/23168367 PubMed]
 
−
 
 
−
==R-CHOP==
 
−
R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
 
−
 
 
−
Synonyms: R-CHOP-21, CHOP-R
 
−
 
 
−
Structured Concept: [http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary==NCI%20Thesaurus&version==12.09d&code==C9760 C9760] (NCI-T), [http://ncim.nci.nih.gov/ncimbrowser/ConceptReport.jsp?dictionary==NCI%20MetaThesaurus&code==C0393023 C0393023] (NCI-MT/UMLS)
 
−
 
 
−
===Regimen #1, Coiffier et al. 2002 (LNH-98.5); Delarue et al. 2013 (LNH03-6B)===
 
−
 
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
<span title=="10-year OS 43.5% (R-CHOP) vs. 27.6% (CHOP) &#10;3-year OS 92% (ACVBP-R) vs. 84% (R-CHOP)"
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Mixed OS</span>
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Similar toxicity</span>
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
*[[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
 
−
 
 
−
'''21-day cycles x 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
 
−
 
 
−
====Neuromeningeal prophylaxis====
 
−
As described in Delarue et al. 2013 (LNH03-6B):
 
−
*[[Methotrexate (MTX)]] 15 mg IT once every 21 days x 4 total doses
 
−
 
 
−
===Regimen #2, Pfreundschuh et al. 2006 & 2011 (MInT)===
 
−
 
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
<span title=="6-year OS 90.1% (R-CHOP) vs. 80% (CHOP-like)"
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Improved OS</span>
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Similar toxicity</span>
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
*[[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; 30-40 Gy to primary extranodal disease at physician discretion
 
−
 
 
−
'''21-day cycles x 6 cycles'''
 
−
 
 
−
*[[Example orders for R-CHOP in lymphoma]]
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] or [[Lenograstim (Granocyte)]] used at physician discretion for neutropenia
 
−
 
 
−
===Regimen #3, Habermann et al. 2006 (CALGB 9793)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days -7 and -3 of cycle 1; then [[Rituximab (Rituxan)]] 375 mg/m2 IV once on day -2 of cycles 2 onwards
 
−
*[[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 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"
 
−
 
 
−
'''21-day cycles x 6 to 8 cycles'''
 
−
 
 
−
===Regimen #4, Merli et al. 2012 (ANZINTER3)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
*[[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 PO/IV once per day on days 1 to 5
 
−
 
 
−
'''21-day cycles x 6 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*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.
 
−
*Erythropoietin use was allowed for hemoglobin <11 g/dL.
 
−
 
 
−
====Radiation therapy====
 
−
''"At the end of chemotherapy, radiotherapy (RT) was scheduled for sites of previous bulky disease or partially responding sites."''
 
−
 
 
−
===Regimen #5, Cunningham et al. 2013===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
''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
 
−
*[[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
 
−
*[[Prednisolone (Millipred)]] 40 mg/m2 PO once per day on days 1 to 5
 
−
 
 
−
'''21-day cycles x 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12 at physician discretion
 
−
*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 chemotherapy is completed
 
−
 
 
−
====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.
 
−
 
 
−
===References===
 
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa011795 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11807147 PubMed]
 
−
# '''Update:''' Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. [http://jco.ascopubs.org/content/23/18/4117.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15867204 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]
 
−
# 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. [http://jco.ascopubs.org/content/24/19/3121.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16754935 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:''' 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/22118442 PubMed]
 
−
# 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. [http://www.sciencedirect.com/science/article/pii/S0140673611610404 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22118442 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]
 
−
# 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. [http://informahealthcare.com/doi/full/10.3109/10428194.2011.621565 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21895543 PubMed]
 
−
# 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. [http://www.sciencedirect.com/science/article/pii/S1470204513701220 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23578722 PubMed]
 
−
# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext?elsca1=ETOC-LANCET&elsca2=email&elsca3=E24A35F link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23615461 PubMed]
 
−
 
 
−
==R-CHOP Intensified==
 
−
R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
 
−
 
 
−
Synonyms: R-CHOP-14, Dose-dense rituximab-CHOP
 
−
 
 
−
Structured Concept: none
 
−
 
 
−
===Regimen #1, Pfreundschuh et al. 2008 (RICOVER-60)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
====Pre-phase treatment====
 
−
*[[Vincristine (Oncovin)]] 1 mg IV once (day not specified)
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 7
 
−
 
 
−
'''7-day course''', then proceed to main R-CHOP-14 regimen
 
−
 
 
−
====Main R-CHOP-14 regimen====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
 
 
−
'''14-day cycles x 6 to 8 cycles (8 doses of rituximab regardless of total number of cycles)'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] or [[Lenograstim (Granocyte)]] (dose/route/frequency not specified) starting on day 4, to continue until count recovery
 
−
 
 
−
====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 #2, Delarue et al. 2013 (LNH03-6B)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[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
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
 
 
−
'''14-day cycles x 8 cycles'''
 
−
 
 
−
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."
 
−
 
 
−
====Neuromeningeal prophylaxis====
 
−
*[[Methotrexate (MTX)]] 15 mg IT once every 14 days x 4 total doses
 
−
 
 
−
===Regimen #3, Cunningham et al. 2013===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
====Main R-CHOP-14 regimen====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
*[[Prednisolone (Millipred)]] 100 mg PO once per day on days 1 to 5
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
 
 
−
'''14-day cycles x 6 cycles; then give additional doses of rituximab as described below'''
 
−
 
 
−
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
 
−
*[[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
 
−
 
 
−
====Additional doses of Rituximab====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
 
 
−
'''14-day cycles x 2 cycles'''
 
−
 
 
−
====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.
 
−
 
 
−
===References===
 
−
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18226581 PubMed]
 
−
# 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. [http://www.sciencedirect.com/science/article/pii/S1470204513701220 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23578722 PubMed]
 
−
# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext?elsca1=ETOC-LANCET&elsca2=email&elsca3=E24A35F link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23615461 PubMed]
 
−
 
 
−
==R-CVP==
 
−
R-CVP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
 
−
 
 
−
Structured Concept: [http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary==NCI%20Thesaurus&version==12.09d&code==C63473 C63473] (NCI-T), [http://ncim.nci.nih.gov/ncimbrowser/ConceptReport.jsp?dictionary==NCI%20MetaThesaurus&code==C1882520 C1882520] (NCI-MT/UMLS)
 
−
 
 
−
===Regimen===
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 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 days1 to 5
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
 
 
−
'''21-day cycles x up to 8 cycles'''
 
−
 
 
−
===References===
 
−
See [[#CVP|references for CVP]]
 
−
 
 
−
==R-miniCEOP==
 
−
R-miniCEOP: '''<u>R</u>'''ituximab, mini, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>O</u>'''?? (vinblastine), '''<u>P</u>'''rednisone
 
−
 
 
−
===Regimen, Merli et al. 2012 (ANZINTER3)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 50 mg/m2 IV once on day 1
 
−
*[[Vinblastine (Velban)]] 5 mg/m2 IV once on day 1
 
−
*[[Prednisone (Sterapred)]] 50 mg/m2 PO/IV once per day on days 1 to 5
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
 
 
−
'''21-day cycles x 6 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*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.
 
−
*Erythropoietin use was allowed for hemoglobin <11 g/dL.
 
−
 
 
−
====Radiation therapy====
 
−
''"At the end of chemotherapy, radiotherapy (RT) was scheduled for sites of previous bulky disease or partially responding sites."''
 
−
 
 
−
===References===
 
−
# 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. [http://informahealthcare.com/doi/full/10.3109/10428194.2011.621565 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21895543 PubMed]
 
−
 
 
−
==R2CHOP, LR-CHOP-21==
 
−
R2CHOP: '''<u>R</u>'''ituximab, '''<u>R</u>'''evlimid, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
 
−
LR-CHOP-21: '''<u>L</u>'''enalidomide, '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
 
−
 
 
−
===Regimen #1, Nowakowski et al. 2013===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 10
 
−
*[[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 cycles x up to 6 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Pegfilgrastim (Neulasta)]] SC once on day 2
 
−
*[[Aspirin]] 81 mg PO once per day unless otherwise anticoagulated
 
−
 
 
−
===Regimen #2, Chiappella et al. 2013===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
*[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 14
 
−
*[[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
 
−
 
 
−
'''21-day cycles x 6 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*Granulocyte-colony stimulants with each cycle (agent not specified)
 
−
*Low molecular weight heparin (dose not specified)
 
−
*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] or [[Pentamidine (Nebupent)]]
 
−
*Lamivudine for occult hepatitis B carriers
 
−
 
 
−
===References===
 
−
# 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. [http://www.nature.com/leu/journal/v25/n12/full/leu2011165a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21720383 PubMed]
 
−
# Nowakowski GS et al. Combination of lenalidomide with R-CHOP (R2CHOP) is well-tolerated and effective as initial therapy for aggressive B-cell lymphomas — A Phase II study. Proc ASH 2012; [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/689?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=abstract+689&searchid=1&FIRSTINDEX=0&volume=120&issue=21&resourcetype=HWCIT Abstract 689].
 
−
# Chiappella A et al. Rituximab-CHOP21 plus lenalidomide (LR-CHOP21) is effective and feasible in elderly untreated diffuse large B-cell lymphoma (DLBCL): Results of Phase II REAL07 study of the Fondazione Italiana Linfomi (FIL). Proc ASH 2012; [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/903?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=abstract+903&searchid=1&FIRSTINDEX=0&volume=120&issue=21&resourcetype=HWCIT Abstract 903].
 
−
# 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 Jun 28. [Epub ahead of print] [http://www.haematologica.org/content/early/2013/06/11/haematol.2013.085134.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23812930 PubMed]
 
−
 
 
−
=DLBCL, relapsed/refractory=
 
−
 
 
−
==BR==
 
−
BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Bendamustine (Treanda)]] 120 mg/m2 IV over 60 minutes once per day on days 2 & 3
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
 
 
−
'''21-day cycles x up to 6 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*"Opportunistic infection prophylaxis with trimethoprim-sulfamethoxazole and acyclovir was recommended."
 
−
 
 
−
===References===
 
−
# 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. [http://jco.ascopubs.org/content/31/17/2103.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23650408 PubMed]
 
−
 
 
−
==EPOCH==
 
−
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
 
−
 
 
−
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)
 
−
 
 
−
===Regimen, Wilson et al. 1993 - original EPOCH protocol===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Etoposide (Vepesid)]] 50 mg/m2/day (total dose of 200 mg/m2) IV continuous infusion on days 1 to 4
 
−
*[[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
 
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m2/day (total dose of 40 mg/m2) IV continuous infusion on days 1 to 4
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV over 15 minutes on day 6
 
−
 
 
−
Supportive medications:
 
−
*[[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:
 
−
**[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO BID 3 days per week
 
−
**[[Atovaquone (Mepron)]] 1500 mg PO once per day
 
−
**Pentamidine (Nebupent) 300 mg nebulized every 28 days
 
−
 
 
−
'''21-day cycles x 6 to 8 cycles'''
 
−
 
 
−
===References===
 
−
# Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, Kohler DR, Jaffe ES, Herdt J, Cheson BD et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J Clin Oncol. 1993 Aug;11(8):1573-82 [http://jco.ascopubs.org/content/11/8/1573.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/7687667 PubMed]
 
−
 
 
−
==ESHA==
 
−
ESHA: '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>S</u>'''olumedrol (methylprednisolone) '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (cytarabine)
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Etoposide (Vepesid)]] 40 mg/m2 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
 
−
*[[Cytarabine (Cytosar)]] 2000 mg/m2 IV over 2 hours once on day 5
 
−
 
 
−
'''21 to 28 day cycles ("after recovery of the toxic effects") x 6 to 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*At least 1 liter normal saline with 25-50 g mannitol once per day throughout chemotherapy
 
−
*Metoclopramide (Reglan) 0.5-1 mg/kg "given regularly"
 
−
 
 
−
===References===
 
−
# Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. [http://jco.ascopubs.org/content/12/6/1169.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8201379 PubMed]
 
−
 
 
−
==ESHAP==
 
−
ESHAP: '''<u>E</u>'''toposide, '''<u>S</u>'''olumedrol (methylprednisolone) '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (cytarabine), cis'''<u>P</u>'''latin
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Etoposide (Vepesid)]] 40 mg/m2 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
 
−
*[[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
 
−
 
 
−
'''21 to 28 day cycles ("after recovery of the toxic effects") x 6 to 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*At least 1 liter normal saline with 25-50 g mannitol once per day throughout chemotherapy
 
−
*Metoclopramide (Reglan) 0.5-1 mg/kg "given regularly"
 
−
 
 
−
===References===
 
−
# Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. [http://jco.ascopubs.org/content/12/6/1169.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8201379 PubMed]
 
−
 
 
−
==Everolimus==
 
−
===Regimen, Witzig et al. 2011===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Everolimus (Afinitor)]] 10 mg PO once per day on an empty stomach
 
−
 
 
−
'''28-day cycles, given until progression or unacceptable toxicity'''
 
−
 
 
−
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."
 
−
 
 
−
===References===
 
−
# 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. [http://www.nature.com/leu/journal/v25/n2/full/leu2010226a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21135857 PubMed]
 
−
 
 
−
==ICE==
 
−
ICE: '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide
 
−
 
 
−
===Regimen, Zelenetz et al. 2003===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
''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
 
−
*[[Mesna (Mesnex)]] 5,000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together with ifosfamide
 
−
*[[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
 
−
*[[Etoposide (Vepesid)]] 100 mg/m2 IV bolus once per day on days 1 to 3
 
−
 
 
−
'''14-day cycles x 3 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[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)
 
−
 
 
−
===References===
 
−
# 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. [http://annonc.oxfordjournals.org/content/14/suppl_1/i5.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12736224 PubMed]
 
−
 
 
−
==Ifosfamide (Ifex)==
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III, <20 in this arm</span>
 
−
 
 
−
''Dose & schedule is as given in Pettengell et al. The original phase II trial (CALGB 8552) used a different dose & schedule.''
 
−
 
 
−
*[[Ifosfamide (Ifex)]] 3000 mg/m2 IV once per day on days 1 & 2
 
−
*[[Mesna (Mesnex)]] dose not specified
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===References===
 
−
# 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. [http://www.ncbi.nlm.nih.gov/pubmed/1743622 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]
 
−
 
 
−
==Lenalidomide (Revlimid)==
 
−
 
 
−
===Regimen, Wiernik et al. 2008 (NHL-002); Witzig et al. 2011 (NHL-003)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
 
 
−
'''28-day cycles until disease progression or unacceptable toxicity'''
 
−
 
 
−
===References===
 
−
# 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. [http://jco.ascopubs.org/content/26/30/4952.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18606983 PubMed]
 
−
# 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. [http://annonc.oxfordjournals.org/content/22/7/1622.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21228334 PubMed]
 
−
 
 
−
==Lenalidomide & Rituximab==
 
−
 
 
−
===Regimen #1, Zinzani et al. 2011===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
====Induction====
 
−
*[[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
 
−
 
 
−
'''28-day cycles x 4 cycles; patients with response of stable disease or better received:'''
 
−
 
 
−
====Maintenance====
 
−
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 
−
 
 
−
'''28-day cycles x 8 months'''
 
−
 
 
−
===Regimen #2, Wang et al. 2013===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[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
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===References===
 
−
# 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. [http://www.sciencedirect.com/science/article/pii/S2152265011000231 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21859554 PubMed]
 
−
# 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. [http://www.nature.com/leu/journal/v27/n9/full/leu201395a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23545991 PubMed]
 
−
 
 
−
==MINE-ESHAP==
 
−
MINE: '''<u>M</u>'''esna, '''<u>I</u>'''fosfamide, '''<u>N</u>ovantrone''', '''<u>E</u>'''toposide
 
−
ESHAP: '''<u>E</u>'''toposide, '''<u>H</u>'''igh dose '''<u>A</u>'''ra-C, '''<u>P</u>'''latinol
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
===Part 1: MINE===
 
−
*[[Mesna (Mesnex)]] 4 g/m2 IV divided over three days, administered over 1 hour
 
−
*[[Ifosfamide (Ifex)]] 4 g/m2 IV divided over three days, administered over 1 hour
 
−
*[[Mesna (Mesnex)]] 500 mg diluted in water or juice, 4 hours following ifosfamide administration
 
−
*[[Mitoxantrone (Novantrone)]] 8 g/m2 IV once on day 1
 
−
*[[Etoposide (Vepesid)]] 65 mg/m2 IV over 1 hour once per day on days 1 to 3
 
−
 
 
−
===Part 2: ESHAP===
 
−
*[[Etoposide (Vepesid)]] 60 mg/m2 IV over 1 hour once per day on days 1 to 4
 
−
*[[Methylprednisolone (Solumedrol)]] 500 mg IV as a short infusion once per day on days 1 to 4
 
−
*[[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
 
−
 
 
−
'''21-day cycles; patients who achieved a CR received a total of 6 cycles of MINE and then 3 cycles of ESHAP as consolidation therapy. If patients achieved a PR, then MINE was given to the point of maximal response, and then patients were crossed over to ESHAP.'''
 
−
 
 
−
===References===
 
−
# Rodriguez MA, Cabanillas FC, Velasquez W, Hagemeister FB, McLaughlin P, Swan F, Romaguera JE. Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP. J Clin Oncol. 1995 Jul;13(7):1734-41. [http://jco.ascopubs.org/content/13/7/1734.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/7602363 PubMed]
 
−
 
 
−
==Obinutuzumab (GA101)==
 
−
 
 
−
===Regimen, Morschhauser et al. 2013 (GAUGUIN)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Obinutuzumab (GA101)]] 1600 mg (diluted to 10 mg/mL) IV once per day on cycle 1 days 1 & 8; then, during cycles 2 to 8, [[Obinutuzumab (GA101)]] 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.
 
−
 
 
−
'''21-day cycles x 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*Acetaminophen (Tylenol) or paracetamol 650 to 1000 mg PO once 30 minutes prior to obinutuzumab
 
−
*"An antihistamine" 30 minutes prior to obinutuzumab; if there were no infusion-related reactions (IRRs) requiring medication or infusion interruption, antihistamine could be omitted for subsequent infusions
 
−
*Premedication with [[Steroid conversions|corticosteroids]] recommended for patients at high risk of infusion-related reactions (IRRs)
 
−
*Use of [[Filgrastim (Neupogen)|G-CSF]] allowed for severe neutropenia
 
−
*Antibiotic prophylaxis allowed
 
−
 
 
−
===References===
 
−
# 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. [http://jco.ascopubs.org/content/31/23/2912.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23835718 PubMed]
 
−
 
 
−
==O-DHAP==
 
−
O-DHAP: '''<u>O</u>'''fatumumab, '''<u>D</u>'''examethasone, '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (cytarabine), cis'''<u>P</u>'''latin
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Ofatumumab (Arzerra)]] 1000 mg IV on cycle 1 days 1 & 8; then on day 1 only of cycles 2 & 3 (total of 4 doses)
 
−
*[[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)
 
−
*[[Cisplatin (Platinol)]] 100 mg/m2 IV continuous infusion over 24 hours on day 1
 
−
 
 
−
'''21-day cycles x 3 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen) | G-CSF]] or [[Pegfilgrastim (Neulasta) | Neulasta]] was recommended (no details given).
 
−
 
 
−
===References===
 
−
# 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. [http://bloodjournal.hematologylibrary.org/content/122/4/499.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23692856 PubMed]
 
−
 
 
−
==O-ICE==
 
−
O-ICE: '''<u>O</u>'''fatumumab, '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Ofatumumab (Arzerra)]] 1000 mg IV on cycle 1 days 1 & 8; then on day 1 only of cycles 2 & 3 (total of 4 doses)
 
−
*[[Ifosfamide (Ifex)]] 5,000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together with mesna
 
−
*[[Mesna (Mesnex)]] 5,000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together with ifosfamide
 
−
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg per cycle) IV once on day 1 or 2 (1 dose, total)
 
−
**Carboplatin AUC calculated based on a 12-hour creatinine clearance
 
−
*[[Etoposide (Vepesid)]] 100 mg/m2 IV once per day on days 1 to 3
 
−
 
 
−
'''21-day cycles x 3 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen) | G-CSF]] or [[Pegfilgrastim (Neulasta) | Neulasta]] was recommended (no details given).
 
−
 
 
−
===References===
 
−
# 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. [http://bloodjournal.hematologylibrary.org/content/122/4/499.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23692856 PubMed]
 
−
 
 
−
==Oxaliplatin (Eloxatin)==
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
''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.''
 
−
 
 
−
*[[Oxaliplatin (Eloxatin)]] 100 to 130 mg/m2 IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
# 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. [http://annonc.oxfordjournals.org/content/10/3/351.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10355582 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]
 
−
# 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]
 
−
 
 
−
==Pixantrone (Pixuvri)==
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Pixantrone (Pixuvri)]] 85 mg/m2 IV once per day on days 1, 8, 15
 
−
 
 
−
'''28-day cycles x up to 6 cycles'''
 
−
 
 
−
===References===
 
−
# 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]
 
−
 
 
−
==R-DHAP==
 
−
R-DHAP: '''<u>R</u>'''ituximab, '''<u>D</u>'''examethasone, '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (cytarabine), cis'''<u>P</u>'''latin
 
−
 
 
−
===Regimen, Gisselbrecht et al. 2010 (CORAL)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV on cycle 1 day -1 & 1; then on cycle 2 and on, [[Rituximab (Rituxan)]] is 375 mg/m2 IV once on day 1; given first before other chemotherapy
 
−
*[[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)
 
−
*[[Cisplatin (Platinol)]] 100 mg/m2 IV continuous infusion over 24 hours on day 1
 
−
 
 
−
'''21-day cycles x 3 cycles'''; patients with complete or partial response then received [[Transplant conditioning regimens#Regimen_.234.2C_Gisselbrecht.2C_et_al._2010 | BEAM chemotherapy]] & autologous stem-cell transplant (ASCT)
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen) | G-CSF]] "depending on site policy, with R-DHAP, but always after the third cycle until the end of leukaphereses"
 
−
 
 
−
===References===
 
−
# 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. [http://annonc.oxfordjournals.org/content/17/suppl_4/iv31.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/16702182 PubMed]
 
−
# 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. [http://jco.ascopubs.org/content/28/27/4184.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20660832 PubMed]
 
−
 
 
−
==R-GDP==
 
−
R-GDP: '''<u>R</u>'''ituximab, '''<u>G</u>'''emcitabine, '''<u>D</u>'''examethasone, '''<u>P</u>'''latinol
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Non-randomized</span>
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once per day on days 1 & 8
 
−
*[[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
 
−
 
 
−
'''21-day cycles x up to 6 cycles'''
 
−
 
 
−
===References===
 
−
# 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. [http://link.springer.com/article/10.1007%2Fs12032-012-0211-2 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/22476761 PubMed]
 
−
 
 
−
==R-ESHAP==
 
−
R-ESHAP: '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>S</u>'''olumedrol (methylprednisolone) '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (cytarabine), cis'''<u>P</u>'''latin
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#ff0000;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Retrospective</span>
 
−
 
 
−
''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)
 
−
*[[Etoposide (Vepesid)]] 40 mg/m2 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
 
−
**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
 
−
 
 
−
'''21 to 28 day cycles ("after recovery of the toxic effects") x 6 to 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*At least 1 liter normal saline with 25-50 g mannitol once per day throughout chemotherapy
 
−
*Metoclopramide (Reglan) 0.5-1 mg/kg "given regularly"
 
−
 
 
−
===References===
 
−
# Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. [http://jco.ascopubs.org/content/12/6/1169.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8201379 PubMed]
 
−
# 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. [http://www.haematologica.org/content/93/12/1829.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18945747 PubMed]
 
−
 
 
−
==R-ICE==
 
−
R-ICE: '''<u>R</u>'''ituximab, '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide
 
−
 
 
−
===Regimen #1, Zelenetz et al. 2003 & Kewalramani et al. 2004===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
''Third cycle intended to be followed by peripheral blood stem cell collection''
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
**An additional one-time dose of [[Rituximab (Rituxan)]] 375 mg/m2 IV was given 48 hours before the beginning of cycle 1
 
−
*[[Ifosfamide (Ifex)]] 5,000 mg/m2 IV continuous infusion over 24 hours on day 4, mixed together with mesna
 
−
*[[Mesna (Mesnex)]] 5,000 mg/m2 IV continuous infusion over 24 hours on day 4, mixed together with ifosfamide
 
−
*[[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
 
−
*[[Etoposide (Vepesid)]] 100 mg/m2 IV bolus once per day on days 3 to 5
 
−
 
 
−
'''14-day cycles x 3 cycles'''
 
−
 
 
−
Supportive medications (as described by Kewalramani et al. 2004):
 
−
*Acetaminophen (Tylenol) 650 mg PO once as premedication for rituximab
 
−
*Diphenhydramine (Benadryl) 50 mg IV once as premedication for rituximab
 
−
*[[Filgrastim (Neupogen)]] 5 μg/kg SC once per day on days 7 to 14 (10 μg/kg with cycle 3, given until collection of peripheral blood stem cells)
 
−
 
 
−
===Regimen #2, Gisselbrecht et al. 2010 (CORAL)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#00CD00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III</span>
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV on cycle 1 day -1 & 1; then on cycle 2 and on, [[Rituximab (Rituxan)]] is 375 mg/m2 IV once on day 1; given first before other chemotherapy
 
−
*[[Ifosfamide (Ifex)]] 5,000 mg/m2 IV continuous infusion over 24 hours on day 2
 
−
*[[Mesna (Mesnex)]] given with ifosfamide; dose & schedule not specified in the paper
 
−
*[[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
 
−
 
 
−
'''21-day cycles x 3 cycles'''; patients with complete or partial response then received [[Transplant conditioning regimens#Regimen_.234.2C_Gisselbrecht.2C_et_al._2010 | BEAM chemotherapy & autologous stem-cell transplant (ASCT)]]
 
−
 
 
−
Supportive medications:
 
−
*"[[Filgrastim (Neupogen) | Granulocyte colony-stimulating factor]] was administered after R-ICE"
 
−
 
 
−
===References===
 
−
# 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. [http://annonc.oxfordjournals.org/content/14/suppl_1/i5.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12736224 PubMed]
 
−
# 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. [http://bloodjournal.hematologylibrary.org/content/103/10/3684.long link to original article] '''contains regimen''' [http://www.ncbi.nlm.nih.gov/pubmed/14739217 PubMed]
 
−
# 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. [http://annonc.oxfordjournals.org/content/17/suppl_4/iv31.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/16702182 PubMed]
 
−
# 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. [http://jco.ascopubs.org/content/28/27/4184.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20660832 PubMed]
 
−
 
 
−
==Temsirolimus (Torisel)==
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once per week
 
−
 
 
−
'''28-day cycles x up to 6 cycles'''
 
−
 
 
−
===References===
 
−
# 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. [http://jco.ascopubs.org/content/28/31/4740.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20837940 PubMed]
 
−
 
 
−
==Vinorelbine (Navelbine)==
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase III, <20 in this arm</span>
 
−
 
 
−
*[[Vinorelbine (Navelbine)]] 30 mg/m2 IV once per day on days 1, 8, 15, 22
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===References===
 
−
# 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]
 
−
# 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]
 
−
 
 
−
=BL or Burkitt-like Lymphoma, untreated=
 
−
==BASIC==
 
−
BASIC: Brief, anthracycline-sparing, intensive cyclophosphamide
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Non-randomized</span>
 
−
 
 
−
====Induction====
 
−
*[[Cyclophosphamide (Cytoxan)]] 1500 mg/m2 IV over 1 hour once on day 1
 
−
*[[Mesna (Mesnex)]] 900 mg/m2 IV "in divided doses" on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (max dose of 2 mg) IV once on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1 & 8
 
−
*[[Methotrexate (MTX)]] 3000 mg/m2 IV over 2 hours on day 8
 
−
*[[Folinic acid (Leucovorin)]] 25 mg/m2 IV Q6H, starting 24 hours 8after start of IV methotrexate, until clearance
 
−
*[[Cytarabine (Cytosar)]] 100 mg intrathecal (50 mg of hydrocortisone optional) on days 1, 4, 11 (also day 8 if no IV MTX given)
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC daily, starting on day 3 and continuing until post-nadir ANC >500/uL
 
−
 
 
−
'''14-day cycles x 2 cycles, then:'''
 
−
 
 
−
====Intensification====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg/kg IV over 1 to 2 hours once per day on days 2 to 5
 
−
*[[Mesna (Mesnex)]] 40 mg/kg/day IV "in divided doses" on days 2 to 5
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC daily, starting on day 11 and continuing until post-nadir ANC >1000/uL
 
−
 
 
−
'''One course, followed by:'''
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per week x 4 doses, once post-nadir ANC > 1000/uL
 
−
*[[Cytarabine (Cytosar)]] 100 mg intrathecal (50 mg of hydrocortisone optional) once per week x 4 doses, then once every other week x 4 doses
 
−
 
 
−
''Cytarabine only given in prior CNS involvement''
 
−
 
 
−
===References===
 
−
# Kasamon YL, Brodsky RA, Borowitz MJ, Ambinder RF, Crilley PA, Cho SY, Tsai HL, Smith BD, Gladstone DE, Carraway HE, Huff CA, Matsui WH, Bolaños-Meade J, Jones RJ, Swinnen LJ. Brief intensive therapy for older adults with newly diagnosed Burkitt or atypical Burkitt lymphoma/leukemia. Leuk Lymphoma. 2013 Mar;54(3):483-90. Epub 2012 Aug 17. [http://informahealthcare.com/doi/full/10.3109/10428194.2012.715346 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22835045 PubMed]
 
−
 
 
−
==CODOX-M/IVAC (Modified Magrath)==
 
−
CODOX-M: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>DOX</u>'''orubicin, '''<u>M</u>''' ethotrexate
 
−
 
 
−
IVAC: '''<u>I</u>'''fosfamide, '''<u>V</u>'''epesid (etoposide), '''<u>AC</u>''' Ara-C (cytarabine)
 
−
 
 
−
===Regimen===
 
−
====Part 1: CODOX-M====
 
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m2 IV once on day 1; 200 mg/m2 IV once daily on days 2 to 5
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m2 (max dose of 2 mg) IV once on days 1, 8
 
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m2 IV once on day 1
 
−
*[[Cytarabine (Cytosar)]] 70 mg intrathecal on days 1, 3
 
−
 
 
−
Age 65 years or younger:
 
−
*[[Methotrexate (MTX)]] 300 mg/m2 IV over 1 hour on day 10
 
−
*[[Methotrexate (MTX)]] 2700 mg/m2 IV over next 23 hours on day 10
 
−
 
 
−
Age more than 65 years:
 
−
*[[Methotrexate (MTX)]] 100 mg/m2 IV over 1 hour on day 10
 
−
*[[Methotrexate (MTX)]] 900 mg/m2 IV over next 23 hours on day 10
 
−
 
 
−
*[[Folinic acid (Leucovorin)]] 15 mg/m2 IV Q3H, starting 36 hours after start of IV methotrexate until 48 hours, then Q6H until methotrexate level undetectable
 
−
 
 
−
*[[Methotrexate (MTX)]] 12 mg intrathecal on day 15
 
−
*[[Folinic acid (Leucovorin)]] 15 mg PO once 24 hours after intrathecal methotrexate
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SQ daily, starting on day 13 and continuing until ANC >1,000/uL
 
−
 
 
−
====Part 2: IVAC====
 
−
 
 
−
Age 65 years or younger:
 
−
*[[Cytarabine (Cytosar)]] 2 g/m2 IV over 3 hours Q12H on days 1,2 (4 doses)
 
−
*[[Etoposide (Vepesid)]] 60 mg/m2 IV over 1 hour on days 1 to 5
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m2 IV over 1 hour on days 1 to 5
 
−
*[[Mesna (Mesnex)]] 300 mg/m2 (mixed with ifosfamide) over 1 hour, then 300mg/m2 IV every four hours x 2, on days 1 to 5
 
−
 
 
−
Age more than 65 years:
 
−
*[[Cytarabine (Cytosar)]] 1 g/m2 IV over 3 hours Q12H on days 1,2 (4 doses)
 
−
*[[Etoposide (Vepesid)]] 60 mg/m2 IV over 1 hour on days 1 to 5
 
−
*[[Ifosfamide (Ifex)]] 1000 mg/m2 IV over 1 hour on days 1 to 5
 
−
*[[Mesna (Mesnex)]] 200 mg/m2 (mixed with ifosfamide) over 1 hour, then 200mg/m2 IV every four hours x 2, on days 1 to 5
 
−
 
 
−
*[[Methotrexate (MTX)]] 12 mg intrathecal on day 5
 
−
*[[Folinic acid (Leucovorin)]] 15 mg PO once 24 hours after intrathecal methotrexate
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SQ daily, starting on day 7 and continuing until ANC >1,000/uL
 
−
 
 
−
===References===
 
−
# Magrath I, Adde M, Shad A, Venzon D, Seibel N, Gootenberg J, Neely J, Arndt C, Nieder M, Jaffe E, Wittes RA, Horak ID. Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol. 1996 Mar;14(3):925-34. [http://jco.ascopubs.org/content/14/3/925.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8622041 PubMed]
 
−
# Mead GM, Sydes MR, Walewski J, Grigg A, Hatton CS, Pescosta N, Guarnaccia C, Lewis MS, McKendrick J, Stenning SP, Wright D; UKLG LY06 collaborators. An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt's lymphoma: results of United Kingdom Lymphoma Group LY06 study. Ann Oncol. 2002 Aug;13(8):1264-74. Erratum in: Ann Oncol. 2002 Dec;13(12):1961. Norbert, P [corrected to Pescosta, N]. [http://annonc.oxfordjournals.org/content/13/8/1264.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12181251 PubMed]
 
−
# Mead GM, Barrans SL, Qian W, Walewski J, Radford JA, Wolf M, Clawson SM, Stenning SP, Yule CL, Jack AS; UK National Cancer Research Institute Lymphoma Clinical Studies Group; Australasian Leukaemia and Lymphoma Group. A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial). Blood. 2008 Sep 15;112(6):2248-60. Epub 2008 Jul 8. [http://bloodjournal.hematologylibrary.org/content/112/6/2248.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18612102 PubMed]
 
−
# Maruyama D, Watanabe T, Maeshima AM, Nomoto J, Taniguchi H, Azuma T, Mori M, Munakata W, Kim SW, Kobayashi Y, Matsuno Y, Tobinai K. Modified cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy with or without rituximab in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL. Int J Hematol. 2010 Dec;92(5):732-43. Epub 2010 Dec 1. [http://link.springer.com/article/10.1007%2Fs12185-010-0728-0 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21120644 PubMed]
 
−
 
 
−
==DA-R-EPOCH==
 
−
DA-R-EPOCH: '''<u>D</u>'''ose '''<u>A</u>'''djusted '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin
 
−
 
 
−
Synonyms: DA-EPOCH-R, EPOCH-R, REPOCH
 
−
 
 
−
Structured Concept: [http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary==NCI%20Thesaurus&version==12.09d&code==C63461 C63461] (NCI-T), [http://ncim.nci.nih.gov/ncimbrowser/ConceptReport.jsp?dictionary==NCI%20MetaThesaurus&code==C1882521 C1882521] (NCI-MT/UMLS)
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
''Note: the abstract references Wilson et al. 2002 for dosing, however this is the DA-EPOCH regimen (no rituximab). Thus, we are extrapolating that rituximab was given on day 1 of each cycle based on similar protocols in DLBCL and PMBCL.''
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per cycle or day 1 before the start of EPOCH (depending on reference)
 
−
*[[Etoposide (Vepesid)]] 50 mg/m2/day (total dose of 200 mg/m2) IV continuous infusion on days 1 to 4
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO BID on days 1 to 5
 
−
*[[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 once over 15 minutes on day 5
 
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m2/day (total dose of 40 mg/m2) IV continuous infusion on days 1 to 4
 
−
 
 
−
*[[Methotrexate (MTX)]] IT prophylaxis (dose and # of cycles not specified)
 
−
 
 
−
'''21-day cycles x 6 cycles''' OR
 
−
'''21-day cycles x 3 to 6 cycles for 1 cycle beyond CR for a minimum of 3 cycles, if HIV-positive'''
 
−
 
 
−
Dose-adjustments for EPOCH protocol, based on Wilson et al. 2002:
 
−
*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.
 
−
*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 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.
 
−
 
 
−
Supportive medications:
 
−
[[Filgrastim (Neupogen)]] dose not specified once per day, starting on day 6 and continuing until ANC greater than 5 × 10e9/L above the nadir level
 
−
 
 
−
===References===
 
−
# Dunleavy K, Little RF, Pittaluga S, Grant N, Shovlin M, Steinberg S, Yarchoan R, Janik J, Jaffe ES, Wilson WH. A prospective study of dose-adjusted (DA) EPOCH with rituximab in adults with newly diagnosed Burkitt lymphoma: a regimen with high efficacy and low toxicity. Ann Oncol 19(suppl4):83-84, abstr.9. 2008 Jun. [http://annonc.oxfordjournals.org/content/19/suppl_4.toc link to original article] '''contains protocol'''
 
−
 
 
−
==R-CODOX-M/R-IVAC==
 
−
R-CODOX-M: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>DOX</u>'''orubicin, '''<u>M</u>''' ethotrexate
 
−
 
 
−
R-IVAC: '''<u>R</u>'''ituximab, '''<u>I</u>'''fosfamide, '''<u>V</u>'''epesid (etoposide), '''<u>AC</u>''' Ara-C (cytarabine)
 
−
 
 
−
===Part 1: R-CODOX-M===
 
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m2 IV once on day 1; 200 mg/m2 IV once daily on days 2 to 5
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m2 (max dose of 2 mg) IV once on days 1, 8
 
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m2 IV once on day 1
 
−
*[[Cytarabine (Cytosar)]] 40 mg intrathecal on days 1, 3 (more if CNS disease present)
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 on day 6 of cycle 1, then 2 days prior to each subsequent cycle
 
−
 
 
−
*[[Methotrexate (MTX)]] 536 mg/m2 IV over 1 hour on day 10
 
−
*[[Methotrexate (MTX)]] 107 mg/m2/hr IV over next 23 hours on day 10
 
−
 
 
−
*[[Folinic acid (Leucovorin)]] starting 36 hours after start of IV methotrexate until 48 hours, then Q6H until methotrexate level undetectable
 
−
 
 
−
* "Commence leucovorin 36 h after the start of MTX infusion; 85.7 mg/m2 i.v. at 36 h and 12 mg/m2 every 6 h thereafter until the serum MTX level is less than 0.05 μM. Leucovorin 12 mg/m2 is given orally first if patients were without nausea; otherwise i.v. administration is allowed."
 
−
 
 
−
*[[Methotrexate (MTX)]] 15 mg intrathecal on day 15
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SQ daily, starting on day 7 and continuing until ANC >1,000/uL
 
−
 
 
−
===Part 2: R-IVAC===
 
−
 
 
−
*[[Cytarabine (Cytosar)]] 2 g/m2 IV over 3 hours Q12H on days 1,2 (4 doses)
 
−
*[[Etoposide (Vepesid)]] 60 mg/m2 IV over 1 hour on days 1 to 5
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m2 IV over 2 hours on days 1 to 5
 
−
*[[Mesna (Mesnex)]] 300 mg/m2 (mixed with ifosfamide) over 1 hour, then 300mg/m2 IV every four hours x 2, on days 1 to 5
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 on day 6 of cycle 1, then 2 days prior to each subsequent cycle
 
−
 
 
−
*[[Methotrexate (MTX)]] 15 mg intrathecal on day 5
 
−
*[[Cytarabine (Cytosar)]] 40 mg intrathecal on days 7, 9 ONLY if CNS disease present
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SQ daily, starting on day 7 and continuing until ANC >1,000/uL
 
−
 
 
−
===References===
 
−
# Maruyama D, Watanabe T, Maeshima AM, Nomoto J, Taniguchi H, Azuma T, Mori M, Munakata W, Kim SW, Kobayashi Y, Matsuno Y, Tobinai K. Modified cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy with or without rituximab in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL. Int J Hematol. 2010 Dec;92(5):732-43. Epub 2010 Dec 1. [http://link.springer.com/article/10.1007%2Fs12185-010-0728-0 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21120644 PubMed]
 
−
 
 
−
=Gastric DLBCL, untreated=
 
−
 
 
−
==Helicobacter pylori eradication therapy==
 
−
 
 
−
===Regimen===
 
−
 
 
−
Before 1996:
 
−
*Amoxicillin 500mg PO q6h x 28 days
 
−
*Metronidazole 250mg PO q6h x 28 days
 
−
*EITHER bismuth subcitrate 120mg PO q6h x 28 days
 
−
*OR omeprazole 20mg PO BID x 28 days
 
−
 
 
−
After 1996:
 
−
*Amoxicillin 500mg PO q6h x 14 days
 
−
*Clarithromycin 500mg PO BID x 14 days
 
−
*Omeprazole 20mg PO BID x 14 days
 
−
 
 
−
===References===
 
−
# 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. [http://bloodjournal.hematologylibrary.org/content/119/21/4838.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/22403257 PubMed]
 
−
 
 
−
=Anaplastic large-cell lymphoma, relapsed/refractory=
 
−
 
 
−
==Brentuximab vedotin==
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg IV over 30 minutes on day 1
 
−
 
 
−
'''Every 21 days up to 16 infusions'''
 
−
 
 
−
===References===
 
−
#  Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, Matous J, Ramchandren R, Fanale M, Connors JM, Yang Y, Sievers EL, Kennedy DA, Shustov A. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012 Jun 20;30(18):2190-6. Epub 2012 May 21. [http://jco.ascopubs.org/content/30/18/2190.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/22614995 PubMed]
 
−
 
 
−
=Primary mediastinal B-cell lymphoma, untreated=
 
−
 
 
−
==DA-R-EPOCH==
 
−
 
 
−
DA-R-EPOCH: '''<u>D</u>'''ose '''<u>A</u>'''djusted '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin
 
−
 
 
−
===Regimen, Dunleavy et al. 2013===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV over 3 hours once on day 1
 
−
*[[Etoposide (Vepesid)]] 50 mg/m2/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 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 over 96 hours on days 1 to 4 (total dose per cycle: 1.6 mg/m2; dose was not capped)
 
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m2/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 40 mg/m2)
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV over 2 hours once on day 5
 
−
 
 
−
'''21-day cycles x 6 to 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 300 mcg SQ once per day, starting on day 6 and continuing until ANC >5,000/uL past nadir
 
−
*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] 160/800 mg (or equivalent if allergic) PO once per day on 3 days per week
 
−
**Note: It's assumed this is what the supplement for Dunleavy et al. 2013 meant by "Baxtrim (sulphametoxazole and trimethoprim)"
 
−
*Omeprazole (Prilosec) 20 mg (or equivalent) PO once per day
 
−
*Docusate (Colace) (dose not specified) and Sennosides (Senna) 2 tablets PO BID as needed for constipation
 
−
*Lactulose 20 g PO Q6H as needed for constipation
 
−
*Hepatitis B surface antigen positive patients received daily antiviral therapy until 8 weeks after completion of chemotherapy
 
−
 
 
−
====Dose adjustments====
 
−
*Start cycle 1 as described above.
 
−
*Obtain CBCs twice per week for nadir measurements.
 
−
*If nadir ANC >500, increase etoposide, doxorubicin, and cyclophosphamide by one level (20%) compared to previous cycle.
 
−
*If nadir ANC <500, use same doses as last cycle.
 
−
*If nadir platelet count <25,000, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to the previous cycle.
 
−
 
 
−
===References===
 
−
# Dunleavy K, Pittaluga S, Maeda LS, Advani R, Chen CC, Hessler J, Steinberg SM, Grant C, Wright G, Varma G, Staudt LM, Jaffe ES, Wilson WH. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013 Apr 11;368(15):1408-16. [http://www.nejm.org/doi/full/10.1056/NEJMoa1214561 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1214561/suppl_file/nejmoa1214561_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23574119 PubMed]
 
−
 
 
−
=Transformed lymphoma=
 
−
''Transformed lymphoma, often referred to as Richter's transformation, is typically treated as per the histologic subtype, which is usually DLBCL. However, some regimens specific to transformed lymphoma have been developed and are included here.''
 
−
 
 
−
==<sup>131</sup>Iodine-Tositumomab (Bexxar)==
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
''Also evaluated in low-grade NHL but subtype was not specified.''
 
−
 
 
−
====Dosimetric step====
 
−
*On Day 0, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab & I-131 (Bexxar)|Tositumomab 35 mg labeled with 5 mCi of Iodine-131]] IV over 20 minutes
 
−
**First scan of whole body dosimetry & redistribution
 
−
*Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
 
−
*Day 6 or 7: Third scan of whole body dosimetry & redistribution
 
−
 
 
−
====Therapeutic step====
 
−
*Any day from day 7-14, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab & I-131 (Bexxar)|Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body]] IV over 20 minutes
 
−
***65 cGy total body dose used for patients with platelet counts of 100-150,000/mm3
 
−
''Calculated dose of I-131 is based on information from serial total-body gamma-camera counts''
 
−
 
 
−
===References===
 
−
# Vose JM, Wahl RL, Saleh M, Rohatiner AZ, Knox SJ, Radford JA, Zelenetz AD, Tidmarsh GF, Stagg RJ, Kaminski MS. Multicenter phase II study of iodine-131 tositumomab for chemotherapy-relapsed/refractory low-grade and transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2000 Mar;18(6):1316-23. [http://jco.ascopubs.org/content/18/6/1316.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10715303 PubMed]
 
−
 
 
−
==Lenalidomide (Revlimid)==
 
−
 
 
−
===Regimen, Wiernik et al. 2008 (NHL-002); Witzig et al. 2011 (NHL-003)===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
 
 
−
 
 
−
'''28-day cycles until disease progression or unacceptable toxicity'''
 
−
 
 
−
===References===
 
−
# 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. [http://jco.ascopubs.org/content/26/30/4952.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18606983 PubMed]
 
−
# 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. [http://annonc.oxfordjournals.org/content/22/7/1622.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21228334 PubMed]
 
−
 
 
−
==Lenalidomide & Rituximab==
 
−
===Regimen, Wang et al. 2013===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#ff0000;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II, <20 patients reported</span>
 
−
 
 
−
*[[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
 
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
===References===
 
−
# 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. [http://www.nature.com/leu/journal/v27/n9/full/leu201395a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23545991 PubMed]
 
−
 
 
−
==OFAR==
 
−
OFAR: '''<u>O</u>'''xaliplatin, '''<u>F</u>'''ludarabine, '''<u>A</u>'''ra-C, '''<u>R</u>'''ituximab
 
−
 
 
−
===Regimen===
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Oxaliplatin (Eloxatin)]] 25 mg/m2 IV over 2 hours once daily on days 1 to 4
 
−
*[[Fludarabine (Fludara)]] 30 mg/m2 IV once daily on days 2 & 3, adminstered within 30 minutes of completion of oxaliplantin
 
−
*[[Cytarabine (Cytosar)]] 1000 mg/m2 IV over 2 hours once daily on days 2 & 3, 4 hours after fludarabine started
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV over 4 to 6 hours once on day 3 of cycle 1; then 375 mg/m2 IV over 4 to 6 hours once on day 1 of cycles 2 to 6
 
−
 
 
−
'''28-day cycles x up to 6 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 6
 
−
*Herpes zoster and PCP (Pneumocystis jiroveci pneumonia) prophylaxis used
 
−
 
 
−
===References===
 
−
# Tsimberidou AM, Wierda WG, Plunkett W, Kurzrock R, O'Brien S, Wen S, Ferrajoli A, Ravandi-Kashani F, Garcia-Manero G, Estrov Z, Kipps TJ, Brown JR, Fiorentino A, Lerner S, Kantarjian HM, Keating MJ. Phase I-II study of oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy in patients with Richter's syndrome or fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2008 Jan 10;26(2):196-203. [http://jco.ascopubs.org/content/26/2/196.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18182662 PubMed]
 

Latest revision as of 03:00, 14 October 2017

Aggressive B-cell non-Hodgkin lymphoma regimens have been moved to their histology-specific subtype pages. Please use the links below and/or update your bookmarks.

Diffuse large B-cell lymphoma (DLBCL)

Burkitt lymphoma (BL) or Burkitt-like lymphoma

Mediastinal gray-zone lymphoma (MGZL)

Primary mediastinal B-cell lymphoma (PMBL)

Transformed lymphoma (TL)

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