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=2}}
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==[[Burkitt lymphoma|Burkitt lymphoma (BL) or Burkitt-like lymphoma]]==
  
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=ACVBP-R=
+
==[[Mediastinal gray-zone lymphoma|Mediastinal gray-zone lymphoma (MGZL)]]==
−
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
 
  
−
Synonyms: R-ACVBP
+
==[[Primary mediastinal B-cell lymphoma|Primary mediastinal B-cell lymphoma (PMBL)]]==
  
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Structured Concept: none
+
==[[Transformed lymphoma|Transformed lymphoma (TL)]]==
  
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Level of Evidence:
+
[[Category:Obsolete pages]]
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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>
 
−
 
 
−
==Induction Regimen==
 
−
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m2 IV on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 75 mg/m2 IV on day 1
 
−
*[[Vindesine (Eldisine)]] 2 mg/m2 IV on days 1 & 5
 
−
*[[Bleomycin (Blenoxane)]] 10 units IV on days 1 & 5
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO on days 1-5
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV 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 daily on days 6-13
 
−
 
 
−
==Consolidation Regimen==
 
−
*[[Methotrexate (MTX)]] 3000 mg/m2 IV 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 on day 1
 
−
*[[Etoposide (Vepesid)]] 300 mg/m2 IV on day 1
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m2 IV on day 1
 
−
 
 
−
'''14-day cycles x 4 cycles''', beginning 2 weeks after completion of MTX, then
 
−
 
 
−
*[[Cytarabine (Cytosar)]] 100 mg/m2 SC on days 1-4
 
−
 
 
−
'''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]
 
−
 
 
−
=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==
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV over 15 minutes on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV bolus over 1-2 minutes on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV bolus over 1-2 minutes on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO on days 1-5
 
−
 
 
−
'''21-day cycles x 8 cycles'''
 
−
 
 
−
==Regimen #2, Pfreundschuh, et al. 2004 & Verdonck, et al. 2007==
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO on days 1-5
 
−
 
 
−
'''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 daily on days 4-13
 
−
 
 
−
==Regimen #3, Miller, et al. 1998 - CHOP-21 & radiation==
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV over 15 minutes on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV bolus over 1-2 minutes on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV bolus over 1-2 minutes on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO on days 1-5
 
−
 
 
−
'''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 & 2010, Feugier, et al. 2005 - LNH-98.5==
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
 
−
*[[Prednisone (Sterapred)]] 40 mg/m2 PO on days 1-5
 
−
 
 
−
'''21-day cycles x 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
 
−
 
 
−
==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]
 
−
# 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]
 
−
# 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]
 
−
# 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]
 
−
 
 
−
=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==
 
−
*[[Cyclophosphamide (Cytoxan)]] 1600 mg/m2 IV on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 65 mg/m2 IV on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 IV on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO on days 1-5
 
−
 
 
−
'''14-day cycles x up to 6 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC daily on days 2-11, or until ANC is greater than 10,000
 
−
 
 
−
==Regimen #2, Verdonck, et al. 2007 - I-CHOP==
 
−
 
 
−
Level of Evidence:
 
−
<span
 
−
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;
 
−
border-style:solid;">Phase III</span>
 
−
<span title="6-year OS 50% (CHOP-21) vs. 61% (I-CHOP), p=NS"
 
−
style="background:#EEEE00;
 
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padding:3px 6px 3px 6px;
 
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border-color:black;
 
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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 on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 70 mg/m2 IV on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO on days 1-5
 
−
 
 
−
'''14-day cycles x 6 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC daily on days 2-11
 
−
 
 
−
==Regimen #3, Pfreundschuh, et al. 2004 - CHOP-14==
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO on days 1-5
 
−
 
 
−
'''14-day cycles x 6 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC daily on days 4-13
 
−
 
 
−
==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]
 
−
# 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]
 
−
 
 
−
=CHOPE=
 
−
CHOPE: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone, '''<u>E</u>'''toposide
 
−
 
 
−
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)
 
−
 
 
−
==Regimen==
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO on days 1-5
 
−
*[[Etoposide (Vepesid)]] 100 mg/m2 IV on days days 1-3
 
−
*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
 
−
 
 
−
*[[Example orders for CHOEP in lymphoma]]
 
−
 
 
−
Supportive medications:
 
−
*For 14-day cycles: [[Filgrastim (Neupogen)]] 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC daily on days 4-13
 
−
*[[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]
 
−
 
 
−
=CODOX-M/IVAC=
 
−
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)
 
−
 
 
−
==Part 1: CODOX-M==
 
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m2 IV on day 1; 200 mg/m2 IV on days 2-5
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m2 (max dose of 2 mg) IV on days 1, 8
 
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m2 IV 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 1-5
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m2 IV over 1 hour on days 1-5
 
−
*[[Mesna (Mesnex)]] 300 mg/m2 (mixed with ifosfamide) over 1 hour, then 300mg/m2 IV every four hours x 2, on days 1-5
 
−
 
 
−
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 1-5
 
−
*[[Ifosfamide (Ifex)]] 1000 mg/m2 IV over 1 hour on days 1-5
 
−
*[[Mesna (Mesnex)]] 200 mg/m2 (mixed with ifosfamide) over 1 hour, then 200mg/m2 IV every four hours x 2, on days 1-5
 
−
 
 
−
*[[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==
 
−
# 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. doi: 10.1182/blood-2008-03-145128. 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]
 
−
 
 
−
=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 #1, dose-adjusted EPOCH (DA-EPOCH), Wilson, et al. 2002==
 
−
*[[Etoposide (Vepesid)]] 50 mg/m2/day (total dose of 200 mg/m2) IV continuous infusion on days 1-4
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO BID on days 1-5
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/m2/day (total dose of 1.6 mg/m2) IV continuous infusion on days 1-4
 
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m2/day (total dose of 40 mg/m2) IV continuous infusion on days 1-4
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV over 15 minutes on day 5
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SQ daily, 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 daily
 
−
**Pentamidine (Nebupent) 300 mg nebulized every 28 days
 
−
 
 
−
'''21-day cycles x 6-8 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.
 
−
 
 
−
==Regimen #2, original EPOCH protocol, Wilson, et al. 1993==
 
−
*[[Etoposide (Vepesid)]] 50 mg/m2/day (total dose of 200 mg/m2) IV continuous infusion on days 1-4
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO on days 1-6
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/m2/day (total dose of 1.6 mg/m2) IV continuous infusion on days 1-4
 
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m2/day (total dose of 40 mg/m2) IV continuous infusion on days 1-4
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV over 15 minutes on day 6
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SQ daily, 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 daily
 
−
**Pentamidine (Nebupent) 300 mg nebulized every 28 days
 
−
 
 
−
'''21-day cycles x 6-8 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]
 
−
# 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]
 
−
 
 
−
=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)
 
−
 
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
==Regimen==
 
−
*[[Methotrexate (MTX)]] 200 mg/m2 IV 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 on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 45 mg/m2 IV on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m2 IV on day 1
 
−
*[[Vincristine (Oncovin)]] 1 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
 
−
*[[Dexamethasone (Decadron)]] 6 mg/m2 (no route specified) daily on days 1-5
 
−
 
 
−
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==
 
−
*[[Cyclophosphamide (Cytoxan)]] 650 mg/m2 IV on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m2 IV on day 1
 
−
*[[Etoposide (Vepesid)]] 120 mg/m2 IV on day 1
 
−
*[[Cytarabine (Cytosar)]] 300 mg/m2 IV on day 8
 
−
*[[Bleomycin (Blenoxane)]] 5 units/m2 IV on day 8
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 IV on day 8
 
−
*[[Methotrexate (MTX)]] 120 mg/m2 IV 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 daily on days 1-14
 
−
*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-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 & 2010; Feugier, et al. 2005 - 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>
 
−
<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>
 
−
 
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
 
−
*[[Prednisone (Sterapred)]] 40 mg/m2 PO on days 1-5
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV on day 1
 
−
 
 
−
'''21-day cycles x 8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
 
−
 
 
−
==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>
 
−
 
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO on days 1-5
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV on day 1
 
−
*Radiation therapy: 30-40 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 used at physician discretion for neutropenia
 
−
 
 
−
==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]
 
−
# 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]
 
−
# 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]
 
−
# 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]
 
−
 
 
−
=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
 
−
 
 
−
Structured Concept: none
 
−
 
 
−
==Regimen==
 
−
==Pre-phase==
 
−
*[[Vincristine (Oncovin)]] 1 mg IV on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO on days 1-7
 
−
 
 
−
'''7-day course''', then
 
−
 
 
−
==Main regimen==
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV on day 1
 
−
*[[Prednisone (Sterapred)]] 100 mg PO on days 1-5
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV on day 1
 
−
 
 
−
'''14-day cycles x 6-8 cycles (8 doses of rituximab regardless of total # of cycles)'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] SC daily starting on day 4, to continue until count recovery
 
−
 
 
−
==Radiation therapy (only for patients meeting criteria)==
 
−
*Radiation therapy, 36 Gy to areas of initial bulky disease (masses at least 7.5 cm in diameter) or extranodal involvement
 
−
 
 
−
==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]
 
−
 
 
−
=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 on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
 
−
*[[Prednisone (Sterapred)]] 40 mg/m2 PO on days 1-5
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV on day 1
 
−
 
 
−
'''21-day cycles x up to 8 cycles'''
 
−
 
 
−
==References==
 
−
See [[#CVP|references for CVP]]
 
−
 
 
−
=R-EPOCH=
 
−
R-EPOCH: '''<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: 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==
 
−
*[[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 1-4
 
−
*[[Prednisone (Sterapred)]] 60 mg/m2 PO BID on days 1-5
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/m2/day (total dose of 1.6 mg/m2) IV continuous infusion on days 1-4
 
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m2/day (total dose of 40 mg/m2) IV continuous infusion on days 1-4
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV over 15 minutes on day 5
 
−
 
 
−
'''21-day cycles x 6-8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SQ daily, 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 daily
 
−
**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 6-8 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*EITHER [[Filgrastim (Neupogen)]] 5 mcg/kg SQ daily, 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 daily
 
−
*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==
 
−
# 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]
 
−
# 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]
 

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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