Difference between revisions of "HIV-associated lymphoma"
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''The most common HIV-associated lymphomas are of [[Diffuse_large_B-cell_lymphoma|DLBCL]] or [[Burkitt lymphoma]] histology; plasmablastic lymphoma and primary effusion lymphomas are also frequently seen in advanced-stage HIV/AIDS. In patients with a normal CD4+ T-cell count and well-controlled HIV, the lymphoma is typically treated as per the histologic subtype. For others, regimens specific to HIV-associated lymphoma have been developed and are included here.'' | ''The most common HIV-associated lymphomas are of [[Diffuse_large_B-cell_lymphoma|DLBCL]] or [[Burkitt lymphoma]] histology; plasmablastic lymphoma and primary effusion lymphomas are also frequently seen in advanced-stage HIV/AIDS. In patients with a normal CD4+ T-cell count and well-controlled HIV, the lymphoma is typically treated as per the histologic subtype. For others, regimens specific to HIV-associated lymphoma have been developed and are included here.'' | ||
+ | =Guidelines= | ||
+ | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' | ||
+ | ==NCCN== | ||
+ | *''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480 NCCN Guidelines - B-cell Lymphomas].'' | ||
=Untreated, pre-phase= | =Untreated, pre-phase= | ||
− | == | + | ==CVP {{#subobject:1a817a|Regimen=1}}== |
− | + | CVP: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone | |
− | + | <br>COP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | COP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone | ||
===Regimen {{#subobject:865d9b|Variant=1}}=== | ===Regimen {{#subobject:865d9b|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2006-10-051771 Galicier et al. 2007 (LMB86)] |
− | |style="background-color:#91cf61"|Phase | + | |1992-11 to 2006-01 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> | + | *[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV once on day 1 |
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1 | *[[Vincristine (Oncovin)]] 2 mg IV once on day 1 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day IV or PO on days 1 to 7 | *[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day IV or PO on days 1 to 7 | ||
+ | '''7-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *COPADM induction | + | *[[#COPADM|COPADM]] induction |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''LMB86:''' Galicier L, Fieschi C, Borie R, Meignin V, Daniel MT, Gérard L, Oksenhendler E. Intensive chemotherapy regimen (LMB86) for St Jude stage IV AIDS-related Burkitt lymphoma/leukemia: a prospective study. Blood. 2007 Oct 15;110(8):2846-54. Epub 2007 Jul 3. [ | + | # '''LMB86:''' Galicier L, Fieschi C, Borie R, Meignin V, Daniel MT, Gérard L, Oksenhendler E. Intensive chemotherapy regimen (LMB86) for St Jude stage IV AIDS-related Burkitt lymphoma/leukemia: a prospective study. Blood. 2007 Oct 15;110(8):2846-54. Epub 2007 Jul 3. [https://doi.org/10.1182/blood-2006-10-051771 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17609431/ PubMed] |
=Upfront therapy= | =Upfront therapy= | ||
− | |||
==CHOP {{#subobject:6bef2f|Regimen=1}}== | ==CHOP {{#subobject:6bef2f|Regimen=1}}== | ||
− | + | CHOP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone | |
− | + | <br>CHOP-21: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone every '''<u>21</u>''' days | |
− | |||
− | |||
− | CHOP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>''' | ||
− | <br>CHOP-21: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>''' | ||
<br>ACOP | <br>ACOP | ||
<br>CAVP | <br>CAVP | ||
Line 52: | Line 55: | ||
<br>VACP | <br>VACP | ||
<br>VCAP | <br>VCAP | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:f5ab10|Variant=1}}=== | ===Regimen {{#subobject:f5ab10|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ Kaplan et al. 2005 (AMC010)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ Kaplan et al. 2005 (AMC010)] | ||
− | |style="background-color:#1a9851"|Phase | + | |1998-2002 |
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
|[[#R-CHOP|R-CHOP]] | |[[#R-CHOP|R-CHOP]] | ||
− | |style="background-color:#ffffbf"| | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5 | *[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*Combination antiretrovirals were required | *Combination antiretrovirals were required | ||
− | *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 5 mcg/kg SC once per day from days 4 to 13 or until ANC greater than 10k/ | + | *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 5 mcg/kg SC once per day from days 4 to 13 or until ANC greater than 10k/μL. |
*PCP prophylaxis with ONE of the following: | *PCP prophylaxis with ONE of the following: | ||
− | **[[Trimethoprim | + | **[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] (dose/route/schedule not specified) |
**[[Dapsone (Aczone)]] (dose/route/schedule not specified) | **[[Dapsone (Aczone)]] (dose/route/schedule not specified) | ||
**[[Pentamidine (Nebupent)]] (dose/schedule not specified) | **[[Pentamidine (Nebupent)]] (dose/schedule not specified) | ||
− | |||
'''21-day cycle for 3 cycles for early disease, or minimum of 6 cycles or 2 past CR for advanced disease''' | '''21-day cycle for 3 cycles for early disease, or minimum of 6 cycles or 2 past CR for advanced disease''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *AMC010, patients with stage I, IE, or nonbulky stage II disease: [[#Radiation_therapy|IFRT]] consolidation, beginning 3 weeks after the third cycle of chemotherapy |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''AMC010:''' Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. [ | + | # '''AMC010:''' Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. [https://doi.org/10.1182/blood-2005-04-1437 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15914552/ PubMed] [https://clinicaltrials.gov/study/NCT00003595 NCT00003595] |
− | |||
==CODOX-M {{#subobject:55e8f4|Regimen=1}}== | ==CODOX-M {{#subobject:55e8f4|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CODOX-M: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate | CODOX-M: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:637c6c|Variant=1}}=== | ===Regimen {{#subobject:637c6c|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/cncr.11628 Wang et al. 2003] |
+ | |1988-2000 | ||
|style="background-color:#ffffbe"|Retrospective | |style="background-color:#ffffbe"|Retrospective | ||
|- | |- | ||
|} | |} | ||
''Note: Wang et al. 2003 retrospectively identified 8 HIV+ Burkitt lymphoma patients who had undergone treatment with CODOX-M/IVAC per the NCI 77-04 protocol.'' | ''Note: Wang et al. 2003 retrospectively identified 8 HIV+ Burkitt lymphoma patients who had undergone treatment with CODOX-M/IVAC per the NCI 77-04 protocol.'' | ||
− | |||
*Patients are stratified into high and low risk: | *Patients are stratified into high and low risk: | ||
**Low risk patients must fulfill all of the following criteria: | **Low risk patients must fulfill all of the following criteria: | ||
Line 109: | Line 113: | ||
***Single extraabdominal mass or completely resected abdominal disease | ***Single extraabdominal mass or completely resected abdominal disease | ||
**Any patients which do not meet low risk criteria are classified as high risk | **Any patients which do not meet low risk criteria are classified as high risk | ||
− | |||
''This regimen is for low risk patients.'' | ''This regimen is for low risk patients.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5 | *[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5 | ||
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*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Methotrexate (MTX)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 240 mg/m<sup>2</sup>/hour IV continuous infusion over 23 hours (total dose per cycle: 6720 mg/m<sup>2</sup>) | *[[Methotrexate (MTX)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 240 mg/m<sup>2</sup>/hour IV continuous infusion over 23 hours (total dose per cycle: 6720 mg/m<sup>2</sup>) | ||
− | + | ====CNS therapy, prophylaxis==== | |
− | ====CNS prophylaxis==== | + | *[[Cytarabine (Ara-C)]] by the following age-based criteria: |
− | *[[Cytarabine (Ara-C)]] 70 mg IT once on day 1 | + | **3 years old or older: 70 mg IT once on day 1 |
− | ** | + | **Younger than 3 years old: "appropriately reduced doses" |
− | *[[Methotrexate (MTX)]] 12 mg IT once on day 3 | + | *[[Methotrexate (MTX)]] by the following age-based criteria: |
− | ** | + | **3 years old or older: 12 mg IT once on day 3 |
− | + | **Younger than 3 years old: "appropriately reduced doses" | |
− | ====Supportive | + | ====Supportive therapy==== |
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 192 mg/m<sup>2</sup> IV once on day 11, starting 36 hours after the start of the day 10 methotrexate, then 12 mg/m<sup>2</sup> IV every 6 hours thereafter until serum methotrexate level is less than 50 nmol/L |
− | + | '''3 cycles; each cycle starts on the same day that the patient's ANC is greater than 1000/μL''' | |
− | '''3 cycles; each cycle starts on the same day that the patient's ANC is greater than 1000/ | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | # '''Retrospective:''' Wang ES, Straus DJ, Teruya-Feldstein J, Qin J, Portlock C, Moskowitz C, Goy A, Hedrick E, Zelenetz AD, Noy A. Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer. 2003 Sep 15;98(6):1196-205. [https:// | + | # '''Retrospective:''' Wang ES, Straus DJ, Teruya-Feldstein J, Qin J, Portlock C, Moskowitz C, Goy A, Hedrick E, Zelenetz AD, Noy A. Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer. 2003 Sep 15;98(6):1196-205. [https://doi.org/10.1002/cncr.11628 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12973843/ PubMed] |
− | |||
==CODOX-M/IVAC {{#subobject:4b6b9|Regimen=1}}== | ==CODOX-M/IVAC {{#subobject:4b6b9|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CODOX-M/IVAC: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate alternating with '''<u>I</u>'''fosfamide, '''<u>V</u>'''epesid (etoposide), '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine) | CODOX-M/IVAC: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate alternating with '''<u>I</u>'''fosfamide, '''<u>V</u>'''epesid (etoposide), '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine) | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:4140f7|Variant=1}}=== | ===Regimen {{#subobject:4140f7|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.1996.14.3.925 Magrath et al. 1996 (NCI 77-04)] |
− | |style="background-color:#91cf61"|Phase | + | |1977-1985 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/cncr.11628 Wang et al. 2003] |
+ | |1988-2000 | ||
|style="background-color:#ffffbe"|Retrospective | |style="background-color:#ffffbe"|Retrospective | ||
|- | |- | ||
|} | |} | ||
− | ''Note: the original protocol of Magrath et al. 1996 did not comment on HIV status. Wang et al. 2003 retrospectively identified 8 HIV+ Burkitt lymphoma patients who had undergone treatment with CODOX-M/IVAC.'' | + | ''Note: the original protocol of Magrath et al. 1996 did not comment on HIV status. Wang et al. 2003 retrospectively identified 8 HIV+ Burkitt lymphoma patients who had undergone treatment with CODOX-M/IVAC. CODOX-M and IVAC are given in an alternating fashion for a total of 4 cycles (A, B, A, B). Each cycle starts on the same day that the patient's ANC is greater than 1000/μL.'' |
− | |||
*Patients are stratified into high and low risk: | *Patients are stratified into high and low risk: | ||
**Low risk patients must fulfill all of the following criteria: | **Low risk patients must fulfill all of the following criteria: | ||
Line 157: | Line 157: | ||
***Single extraabdominal mass or completely resected abdominal disease | ***Single extraabdominal mass or completely resected abdominal disease | ||
**Any patients which do not meet low risk criteria are classified as high risk | **Any patients which do not meet low risk criteria are classified as high risk | ||
− | |||
''This regimen is for high-risk patients.'' | ''This regimen is for high-risk patients.'' | ||
− | ====Chemotherapy, | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy, CODOX-M portion (cycles 1 & 3; "Part A")==== | ||
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5 | *[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5 | ||
− | *[[Vincristine (Oncovin)]] | + | *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8 |
− | |||
− | |||
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Methotrexate (MTX)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 240 mg/m<sup>2</sup>/hour IV continuous infusion over 23 hours (total dose per cycle: 6720 mg/m<sup>2</sup>) | *[[Methotrexate (MTX)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 240 mg/m<sup>2</sup>/hour IV continuous infusion over 23 hours (total dose per cycle: 6720 mg/m<sup>2</sup>) | ||
− | ====CNS prophylaxis==== | + | ====CNS prophylaxis, CODOX-M portion (cycles 1 & 3; "Part A")==== |
− | *[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 1 & 3 | + | *[[Cytarabine (Ara-C)]] by the following age-based criteria: |
− | ** | + | **3 years old or older: 70 mg IT once per day on days 1 & 3 |
− | *[[Methotrexate (MTX)]] 12 mg IT once on day 15 | + | **Younger than 3 years old: "appropriately reduced doses" |
− | ** | + | *[[Methotrexate (MTX)]] by the following age-based criteria: |
+ | **3 years old or older: 12 mg IT once on day 15 | ||
+ | **Younger than 3 years old: "appropriately reduced doses" | ||
+ | ====CNS treatment, CODOX-M portion==== | ||
+ | *[[Cytarabine (Ara-C)]] as follows: | ||
+ | **Cycle 1: 70 mg IT once on day 5 (in addition to doses above) | ||
+ | *[[Methotrexate (MTX)]] as follows: | ||
+ | **Cycle 1: 12 mg IT once on day 17 (in addition to dose above) | ||
− | + | ====Supportive therapy, CODOX-M portion (cycles 1 & 3; "Part A")==== | |
− | + | *[[Leucovorin (Folinic acid)]] 192 mg/m<sup>2</sup> IV once on day 11, starting 36 hours after the start of the day 10 methotrexate, then 12 mg/m<sup>2</sup> IV every 6 hours thereafter until serum methotrexate level is less than 50 nmol/L | |
− | + | *[[Sargramostim (Leukine)|GM-CSF]] 7.5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/μL | |
− | + | ====Chemotherapy, IVAC portion (cycles 2 & 4; "Part B")==== | |
− | ====Supportive | + | *[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5, with mesna |
− | *[[Folinic acid | ||
− | *[[Sargramostim (Leukine)|GM-CSF]] 7.5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/ | ||
− | |||
− | ====Chemotherapy, Part B | ||
− | *[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 5 | *[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>) | ||
− | + | ====CNS prophylaxis, IVAC portion (cycles 2 & 4; "Part B")==== | |
− | ====CNS prophylaxis==== | ||
*[[Methotrexate (MTX)]] 12 mg IT once on day 5 | *[[Methotrexate (MTX)]] 12 mg IT once on day 5 | ||
− | |||
Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy during cycle 2: | Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy during cycle 2: | ||
*[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 7 & 9 | *[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 7 & 9 | ||
*[[Methotrexate (MTX)]] 12 mg IT once on day 17 (in addition to dose above) | *[[Methotrexate (MTX)]] 12 mg IT once on day 17 (in addition to dose above) | ||
− | + | ====Supportive therapy, IVAC portion (cycles 2 & 4; "Part B")==== | |
− | ====Supportive | + | *[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup> IV every 3 hours on days 1 to 5, given with ifosfamide |
− | *[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup> IV every 3 hours on days 1 to 5, given | + | *[[Sargramostim (Leukine)|GM-CSF]] 7.5 mcg/kg SC once per day, starting on day 7 and continuing until ANC greater than 1000/μL |
− | *[[Sargramostim (Leukine)|GM-CSF]] 7.5 mcg/kg SC once per day, starting on day 7 and continuing until ANC greater than 1000/ | ||
− | |||
'''4 cycles (see note)''' | '''4 cycles (see note)''' | ||
− | + | </div></div> | |
− | |||
− | |||
===References=== | ===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. [ | + | # '''NCI 77-04:''' 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. [https://doi.org/10.1200/jco.1996.14.3.925 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8622041/ PubMed] |
− | # '''Retrospective:''' Wang ES, Straus DJ, Teruya-Feldstein J, Qin J, Portlock C, Moskowitz C, Goy A, Hedrick E, Zelenetz AD, Noy A. Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer. 2003 Sep 15;98(6):1196-205. [https:// | + | # '''Retrospective:''' Wang ES, Straus DJ, Teruya-Feldstein J, Qin J, Portlock C, Moskowitz C, Goy A, Hedrick E, Zelenetz AD, Noy A. Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer. 2003 Sep 15;98(6):1196-205. [https://doi.org/10.1002/cncr.11628 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12973843/ PubMed] |
==dmCODOX-M - Modified Magrath {{#subobject:0a0210|Regimen=1}}== | ==dmCODOX-M - Modified Magrath {{#subobject:0a0210|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
dmCODOX-M: '''<u>d</u>'''ose-'''<u>m</u>'''odified '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate | dmCODOX-M: '''<u>d</u>'''ose-'''<u>m</u>'''odified '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:a4c94b|Variant=1}}=== | ===Regimen {{#subobject:a4c94b|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532802/ Mead et al. 2008 (MRC/NCRI LY10)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532802/ Mead et al. 2008 (MRC/NCRI LY10)] | ||
− | |style="background-color:#91cf61"| | + | |2002-2005 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
Line 228: | Line 221: | ||
**Any patients which do not meet low risk criteria are classified as high risk | **Any patients which do not meet low risk criteria are classified as high risk | ||
''This regimen is for low risk patients.'' | ''This regimen is for low risk patients.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5 | *[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5 | ||
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8 | *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8 | ||
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1 | ||
− | *[[Methotrexate (MTX)]] | + | *[[Methotrexate (MTX)]] by the following age-based criteria: |
− | ** | + | **65 years old or younger: 300 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 2700 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 3000 mg/m<sup>2</sup>) |
− | ** | + | **Older than 65 years old: 100 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 900 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 1000 mg/m<sup>2</sup>) |
− | + | ====CNS therapy, prophylaxis==== | |
− | ====CNS prophylaxis==== | ||
*[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 1 & 3 | *[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 1 & 3 | ||
*[[Methotrexate (MTX)]] 12 mg IT once on day 15 | *[[Methotrexate (MTX)]] 12 mg IT once on day 15 | ||
− | |||
Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy: | Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy: | ||
*[[Cytarabine (Ara-C)]] 70 mg IT once on day 5 (in addition to doses above) | *[[Cytarabine (Ara-C)]] 70 mg IT once on day 5 (in addition to doses above) | ||
*[[Methotrexate (MTX)]] 12 mg IT once on day 17 (in addition to dose above) | *[[Methotrexate (MTX)]] 12 mg IT once on day 17 (in addition to dose above) | ||
− | *[[Folinic acid | + | ====Supportive therapy==== |
− | + | *[[Leucovorin (Folinic acid)]] 15 mg PO once on day 18, 24 hours after intrathecal methotrexate | |
− | ====Supportive | + | ====Supportive therapy==== |
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> IV every 3 hours for 5 doses on day 11, starting 36 hours after start of the day 10 methotrexate, then 15 mg/m<sup>2</sup> IV every 6 hours until methotrexate level is less than 50 nmol/L |
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 15 mg PO once on day 16, 24 hours after intrathecal methotrexate |
− | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/ | + | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/μL |
*[[Allopurinol (Zyloprim)]] PO and/or [[Rasburicase (Elitek)]] prior to starting chemotherapy | *[[Allopurinol (Zyloprim)]] PO and/or [[Rasburicase (Elitek)]] prior to starting chemotherapy | ||
− | |||
'''3 cycles (see note)''' | '''3 cycles (see note)''' | ||
− | + | ''Note: Each cycle starts on the same day that the patient's ANC is greater than 1000/μL and unsupported (that is, without transfusion) platelet count greater than 75 x 10<sup>9</sup>/L.'' | |
− | ''Note: Each cycle starts on the same day that the patient's ANC is greater than 1000/ | + | </div></div> |
===References=== | ===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. Epub 2008 Jul 8. [ | + | # '''MRC/NCRI LY10:''' 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. [https://doi.org/10.1182/blood-2008-03-145128 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532802/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18612102/ PubMed] |
− | |||
==dmCODOX-M/IVAC - Modified Magrath {{#subobject:de3784|Regimen=1}}== | ==dmCODOX-M/IVAC - Modified Magrath {{#subobject:de3784|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
dmCODOX-M/IVAC: '''<u>d</u>'''ose-'''<u>m</u>'''odified '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate alternating with '''<u>I</u>'''fosfamide, '''<u>V</u>'''epesid (etoposide), '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine) | dmCODOX-M/IVAC: '''<u>d</u>'''ose-'''<u>m</u>'''odified '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate alternating with '''<u>I</u>'''fosfamide, '''<u>V</u>'''epesid (etoposide), '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine) | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:17f796|Variant=1}}=== | ===Regimen {{#subobject:17f796|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532802/ Mead et al. 2008 (MRC/NCRI LY10)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532802/ Mead et al. 2008 (MRC/NCRI LY10)] | ||
− | |style="background-color:#91cf61"| | + | |2002-2005 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: This regimen is for high-risk patients. dmCODOX-M and IVAC are given in an alternating fashion for a total of 4 cycles (A, B, A, B). Each cycle starts on the same day that the patient's ANC is greater than 1000/μL and unsupported (that is, without transfusion) platelet count greater than 75 x 10<sup>9</sup>/L.'' | ||
*Patients are stratified into high and low risk: | *Patients are stratified into high and low risk: | ||
**Low risk patients must fulfill at least 3 of the following criteria: | **Low risk patients must fulfill at least 3 of the following criteria: | ||
Line 281: | Line 270: | ||
***0 or 1 extranodal sites of disease | ***0 or 1 extranodal sites of disease | ||
**Any patients which do not meet low risk criteria are classified as high risk | **Any patients which do not meet low risk criteria are classified as high risk | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ====Chemotherapy, | + | ====Chemotherapy, dmCODOX-M portion (cycles 1 & 3)==== |
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5 | *[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5 | ||
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8 | *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8 | ||
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1 | ||
− | *[[Methotrexate (MTX)]] | + | *[[Methotrexate (MTX)]] by the following age-based criteria: |
− | ** | + | **65 years old or younger: 300 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 2700 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 3000 mg/m<sup>2</sup>) |
− | ** | + | **Older than 65 years old: 100 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 900 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 1000 mg/m<sup>2</sup>) |
− | + | ====CNS prophylaxis, dmCODOX-M portion (cycles 1 & 3)==== | |
− | ====CNS prophylaxis==== | ||
*[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 1 & 3 | *[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 1 & 3 | ||
*[[Methotrexate (MTX)]] 12 mg IT once on day 15 | *[[Methotrexate (MTX)]] 12 mg IT once on day 15 | ||
− | + | ====CNS treatment, dmCODOX-M portion (cycles 1 & 3)==== | |
Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy: | Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy: | ||
*[[Cytarabine (Ara-C)]] 70 mg IT once on day 5 (in addition to doses above) | *[[Cytarabine (Ara-C)]] 70 mg IT once on day 5 (in addition to doses above) | ||
*[[Methotrexate (MTX)]] 12 mg IT once on day 17 (in addition to dose above) | *[[Methotrexate (MTX)]] 12 mg IT once on day 17 (in addition to dose above) | ||
− | + | ====Supportive therapy, dmCODOX-M portion (cycles 1 & 3)==== | |
− | + | *[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> IV every 3 hours for 5 doses on day 11, starting 36 hours after start of the day 10 methotrexate, then 15 mg/m<sup>2</sup> IV every 6 hours until methotrexate level is less than 50 nmol/L | |
− | ====Supportive | + | *[[Leucovorin (Folinic acid)]] 15 mg PO once on day 16, 24 hours after intrathecal methotrexate |
− | *[[Folinic acid | + | *If CNS+: [[Leucovorin (Folinic acid)]] 15 mg PO once on day 18, 24 hours after intrathecal methotrexate |
− | *[[Folinic acid | + | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/μL |
− | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/ | ||
*[[Allopurinol (Zyloprim)]] PO and/or [[Rasburicase (Elitek)]] prior to starting chemotherapy | *[[Allopurinol (Zyloprim)]] PO and/or [[Rasburicase (Elitek)]] prior to starting chemotherapy | ||
− | + | ====Chemotherapy, IVAC portion (cycles 2 & 4)==== | |
− | ====Chemotherapy, | + | *[[Ifosfamide (Ifex)]] by the following age-based criteria: |
− | *[[Ifosfamide (Ifex)]] | + | **65 years old or younger: 1500 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 |
− | ** | + | **Older than 65 years old: 1000 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 |
− | ** | ||
*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | *[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | ||
− | *[[Cytarabine (Ara-C)]] | + | *[[Cytarabine (Ara-C)]] by the following age-based criteria: |
− | ** | + | **65 years old or younger: 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>) |
− | ** | + | **Older than 65 years old: 1000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 4000 mg/m<sup>2</sup>) |
− | + | ====Supportive therapy, IVAC portion (cycles 2 & 4)==== | |
− | ====CNS prophylaxis==== | + | *[[Mesna (Mesnex)]] by the following age-based criteria: |
+ | **65 years old or younger: 300 mg/m<sup>2</sup> (mixed with ifosfamide) IV over 60 minutes once per day on days 1 to 5, then 300 mg/m<sup>2</sup> IV every four hours for 2 doses on days 1 to 5 | ||
+ | **Older than 65 years old: 200 mg/m<sup>2</sup> (mixed with ifosfamide) IV over 60 minutes once per day on days 1 to 5, then 200 mg/m<sup>2</sup> IV every four hours for 2 doses on days 1 to 5 | ||
+ | *[[Leucovorin (Folinic acid)]] 15 mg PO once on day 6, 24 hours after intrathecal methotrexate | ||
+ | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 7 and continuing until ANC greater than 1000/μL | ||
+ | ====CNS prophylaxis, IVAC portion (cycles 2 & 4)==== | ||
*[[Methotrexate (MTX)]] 12 mg IT once on day 5 | *[[Methotrexate (MTX)]] 12 mg IT once on day 5 | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
'''4 cycles (see note)''' | '''4 cycles (see note)''' | ||
− | + | </div></div> | |
− | |||
===References=== | ===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. Epub 2008 Jul 8. [ | + | # '''MRC/NCRI LY10:''' 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. [https://doi.org/10.1182/blood-2008-03-145128 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532802/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18612102/ PubMed] |
==EPOCH, dose-escalated {{#subobject:ded061|Regimen=1}}== | ==EPOCH, dose-escalated {{#subobject:ded061|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
EPOCH: '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin (Vincristine), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin) | EPOCH: '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin (Vincristine), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin) | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:e70b4b|Variant=1}}=== | ===Regimen {{#subobject:e70b4b|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2002-11-3589 Little et al. 2003] |
+ | |1995-04 to 2000-08 | ||
|style="background-color:#91cf61"|Non-randomized | |style="background-color:#91cf61"|Non-randomized | ||
|- | |- | ||
|} | |} | ||
''Note: the paper refers to this regimen as dose-adjusted EPOCH but to avoid confusion with the other version of dose-adjusted EPOCH, we refer to it as dose-escalated EPOCH, here.'' | ''Note: the paper refers to this regimen as dose-adjusted EPOCH but to avoid confusion with the other version of dose-adjusted EPOCH, we refer to it as dose-escalated EPOCH, here.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m<sup>2</sup>) | *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m<sup>2</sup>) | ||
− | |||
*[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m<sup>2</sup>) | *[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m<sup>2</sup>) | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] by the following laboratory-based criteria: |
− | **CD4+ count less than 100/ | + | **CD4+ count less than 100/μL: 187 mg/m<sup>2</sup> IV over 15 minutes once on day 5 |
− | **CD4+ count | + | **CD4+ count more than 100/μL: 375 mg/m<sup>2</sup> IV over 15 minutes once on day 5 |
− | |||
*[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>) | *[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>) | ||
− | + | ====Glucocorticoid therapy==== | |
− | ====Supportive | + | *[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 5 |
− | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC greater than 5000/ | + | ====Supportive therapy==== |
− | + | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC greater than 5000/μL past nadir | |
'''21-day cycle for 6 cycles''' | '''21-day cycle for 6 cycles''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | **In each subsequent cycle, increase cyclophosphamide dose by 187 mg/m<sup>2</sup> (maximum dose 750 mg/m<sup>2</sup>) if the neutrophil nadir is greater than 500/μL and platelet nadir is greater than 25 x 10<sup>9</sup>/L. Decrease dose by 187 mg/m<sup>2</sup> if the neutrophil nadir is less than 500/μL or platelet nadir is less than 25 x 10<sup>9</sup>/L. | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Little RF, Pittaluga S, Grant N, Steinberg SM, Kavlick MF, Mitsuya H, Franchini G, Gutierrez M, Raffeld M, Jaffe ES, Shearer G, Yarchoan R, Wilson WH. Highly effective treatment of acquired immunodeficiency syndrome-related lymphoma with dose-adjusted EPOCH: impact of antiretroviral therapy suspension and tumor biology. Blood. 2003 Jun 15;101(12):4653-9. Epub 2003 Feb 27. [ | + | # Little RF, Pittaluga S, Grant N, Steinberg SM, Kavlick MF, Mitsuya H, Franchini G, Gutierrez M, Raffeld M, Jaffe ES, Shearer G, Yarchoan R, Wilson WH. Highly effective treatment of acquired immunodeficiency syndrome-related lymphoma with dose-adjusted EPOCH: impact of antiretroviral therapy suspension and tumor biology. Blood. 2003 Jun 15;101(12):4653-9. Epub 2003 Feb 27. [https://doi.org/10.1182/blood-2002-11-3589 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12609827/ PubMed] |
− | ==GMALL-R {{#subobject: | + | ==GMALL-R {{#subobject:630893|Regimen=1}}== |
− | |||
− | |||
− | |||
− | |||
GMALL-R: '''<u>G</u>'''erman '''<u>M</u>'''ulticenter Study Group for the Treatment of Adult '''<u>A</u>'''cute '''<u>L</u>'''ymphoblastic '''<u>L</u>'''eukemia, '''<u>R</u>'''ituximab | GMALL-R: '''<u>G</u>'''erman '''<u>M</u>'''ulticenter Study Group for the Treatment of Adult '''<u>A</u>'''cute '''<u>L</u>'''ymphoblastic '''<u>L</u>'''eukemia, '''<u>R</u>'''ituximab | ||
− | + | <div class="toccolours" style="background-color:#c8a2c8"> | |
− | == | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | {| class="wikitable" style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
− | !style="width: | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/cncr.27918 Ribera et al. 2013 (Burkimab)] |
− | |style="background-color:#91cf61"|Phase | + | |Not reported |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | + | ''Note: Numbering of days is based on pre-phase->A->B->C; however, certain patient populations received different ordering of regimen, see below.'' | |
− | ''Numbering of days is based on | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Pre-phase {{#subobject:724602|Variant=1}}=== | |
− | ====Chemotherapy | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | *[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 | *[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 | ||
− | + | '''5-day course, followed by:''' | |
− | ==== | + | </div></div><br> |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Induction {{#subobject:724xbj|Variant=1}}=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy, A cycle==== | ||
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 4 hours once on day 7 | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 4 hours once on day 7 | ||
+ | ====Chemotherapy, A cycle==== | ||
*[[Vincristine (Oncovin)]] 2 mg IV bolus once on day 8 | *[[Vincristine (Oncovin)]] 2 mg IV bolus once on day 8 | ||
− | *[[Methotrexate (MTX)]] 1500 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 8 | + | *[[Methotrexate (MTX)]] by the following age-based criteria: |
− | **Older than 55 years: | + | **55 years old or younger: 1500 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 8 |
+ | **Older than 55 years old: 750 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 8 | ||
*[[Ifosfamide (Ifex)]] 800 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8 to 12 | *[[Ifosfamide (Ifex)]] 800 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8 to 12 | ||
+ | *[[Teniposide (Vumon)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 11 & 12 | ||
+ | *[[Cytarabine (Ara-C)]] by the following age-based criteria: | ||
+ | **55 years old or younger: 150 mg/m<sup>2</sup> IV over 60 minutes twice per day on days 11 & 12 | ||
+ | **Older than 55 years old: 75 mg/m<sup>2</sup> IV over 60 minutes twice per day on days 11 & 12 | ||
+ | ====Glucocorticoid therapy, A cycle==== | ||
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV bolus once per day on days 8 to 12 | *[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV bolus once per day on days 8 to 12 | ||
− | + | ====Supportive therapy, A cycle==== | |
− | + | *[[Leucovorin (Folinic acid)]] (dose/route/schedule not specified), starting 12 hours after methotrexate infusion | |
− | + | ====Targeted therapy, B cycle==== | |
− | |||
− | ====Supportive | ||
− | *[[Folinic acid | ||
− | |||
− | ==== | ||
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 4 hours once on day 28 | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 4 hours once on day 28 | ||
+ | ====Chemotherapy, B cycle==== | ||
*[[Vincristine (Oncovin)]] 2 mg IV bolus once on day 29 | *[[Vincristine (Oncovin)]] 2 mg IV bolus once on day 29 | ||
− | *[[Methotrexate (MTX)]] 1500 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 29 | + | *[[Methotrexate (MTX)]] by the following age-based criteria: |
− | **Older than 55 years: | + | **55 years old or younger: 1500 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 29 |
+ | **Older than 55 years old: 750 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 29 | ||
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV over 60 minutes once per day on days 29 to 33 | *[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV over 60 minutes once per day on days 29 to 33 | ||
+ | *[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 15 minutes once per day on days 32 & 33 | ||
+ | ====Glucocorticoid therapy, B cycle==== | ||
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV bolus once per day on days 29 to 33 | *[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV bolus once per day on days 29 to 33 | ||
− | + | ====Supportive therapy, B cycle==== | |
− | + | *[[Leucovorin (Folinic acid)]] (dose/route/schedule not specified), starting 12 hours after methotrexate infusion | |
− | ====Supportive | + | ====Targeted therapy, C cycle==== |
− | *[[Folinic acid | ||
− | |||
− | ==== | ||
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 4 hours once on day 49 | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 4 hours once on day 49 | ||
+ | ====Chemotherapy, C cycle==== | ||
*[[Vindesine (Eldisine)]] 3 mg/m<sup>2</sup> (maximum dose of 5 mg) IV bolus once on day 50 | *[[Vindesine (Eldisine)]] 3 mg/m<sup>2</sup> (maximum dose of 5 mg) IV bolus once on day 50 | ||
− | *[[Methotrexate (MTX)]] 1500 mg/m<sup>2</sup> IV continuous infusion over 24 hours, | + | *[[Methotrexate (MTX)]] by the following age-based criteria, starting on day 50: |
− | **Older than 55 years: | + | **55 years old or younger: 1500 mg/m<sup>2</sup> IV continuous infusion over 24 hours |
+ | **Older than 55 years old: 750 mg/m<sup>2</sup> IV continuous infusion over 24 hours | ||
+ | *[[Etoposide (Vepesid)]] 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 53 & 54 | ||
+ | *[[Cytarabine (Ara-C)]] by the following age-based criteria, on day 54: | ||
+ | **55 years old or younger: 2000 mg/m<sup>2</sup> IV over 3 hours twice per day | ||
+ | **Older than 55 years old: 1000 mg/m<sup>2</sup> IV over 3 hours twice per day | ||
+ | ====Glucocorticoid therapy, C cycle==== | ||
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV bolus once per day on days 50 to 54 | *[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV bolus once per day on days 50 to 54 | ||
− | + | ====Supportive therapy, C cycle==== | |
− | + | *[[Leucovorin (Folinic acid)]] (dose/route/schedule not specified), starting 12 hours after methotrexate infusion | |
− | + | '''Give regimen by the following age- and stage-based criteria:''' | |
− | + | *'''Advanced stage and younger than 55 years: A->B->C for 2 courses (6 total cycles)''' | |
− | ====Supportive | + | *'''Older than 55 years old: Alternate A & B for 3 courses (6 total cycles)''' |
− | *[[Folinic acid | ||
− | |||
− | '''Give regimen | ||
− | *'''Advanced stage and younger than 55 years: A->B->C | ||
− | *'''Older than 55 years: Alternate A & B | ||
*'''Localized stage: 4 total cycles (unclear from protocol if this means A alternating with B or A->B->C->A)''' | *'''Localized stage: 4 total cycles (unclear from protocol if this means A alternating with B or A->B->C->A)''' | ||
− | + | </div></div><br> | |
− | ====CNS | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Prophylaxis=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====CNS therapy==== | ||
*[[Methotrexate (MTX)]] 15 mg IT once per day on days 1, 8, 12, 29, 33 | *[[Methotrexate (MTX)]] 15 mg IT once per day on days 1, 8, 12, 29, 33 | ||
*[[Cytarabine (Ara-C)]] 40 mg IT once per day on days 1, 8, 12, 29, 33 | *[[Cytarabine (Ara-C)]] 40 mg IT once per day on days 1, 8, 12, 29, 33 | ||
*[[Dexamethasone (Decadron)]] 20 mg IT once per day on days 1, 8, 12, 29, 33 | *[[Dexamethasone (Decadron)]] 20 mg IT once per day on days 1, 8, 12, 29, 33 | ||
− | |||
'''8 doses total''' | '''8 doses total''' | ||
+ | </div></div></div> | ||
===References=== | ===References=== | ||
− | # '''Burkimab:''' Ribera JM, García O, Grande C, Esteve J, Oriol A, Bergua J, González-Campos J, Vall-Llovera F, Tormo M, Hernández-Rivas JM, García D, Brunet S, Alonso N, Barba P, Miralles P, Llorente A, Montesinos P, Moreno MJ, Hernández-Rivas JÁ, Bernal T. Dose-intensive chemotherapy including rituximab in Burkitt's leukemia or lymphoma regardless of human immunodeficiency virus infection status: final results of a phase 2 study (Burkimab). Cancer. 2013 May 1;119(9):1660-8. Epub 2013 Jan 29. [https:// | + | # '''Burkimab:''' Ribera JM, García O, Grande C, Esteve J, Oriol A, Bergua J, González-Campos J, Vall-Llovera F, Tormo M, Hernández-Rivas JM, García D, Brunet S, Alonso N, Barba P, Miralles P, Llorente A, Montesinos P, Moreno MJ, Hernández-Rivas JÁ, Bernal T. Dose-intensive chemotherapy including rituximab in Burkitt's leukemia or lymphoma regardless of human immunodeficiency virus infection status: final results of a phase 2 study (Burkimab). Cancer. 2013 May 1;119(9):1660-8. Epub 2013 Jan 29. [https://doi.org/10.1002/cncr.27918 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23361927/ PubMed] [https://clinicaltrials.gov/study/NCT00388193 NCT00388193] |
==m-BACOD {{#subobject:f471bb|Regimen=1}}== | ==m-BACOD {{#subobject:f471bb|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
m-BACOD: '''<u>m</u>'''ethotrexate (moderate dose), '''<u>B</u>'''leomycin, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>D</u>'''examethasone | m-BACOD: '''<u>m</u>'''ethotrexate (moderate dose), '''<u>B</u>'''leomycin, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>D</u>'''examethasone | ||
− | === | + | <div class="toccolours" style="background-color:#ee6b6e"> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ===Regimen variant #1, "low-dose" #1 {{#subobject:d60b9a|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199706053362304 Kaplan et al. 1997 (ACTG 142)] |
− | |style="background-color:#1a9851"|Phase | + | |1991-1994 |
− | |[[#m-BACOD| | + | |style="background-color:#1a9851"|Phase 3 (E-de-esc) |
− | |style="background-color:#ffffbf"| | + | |[[#m-BACOD|m-BACOD]]; standard-dose |
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
''Note: this is of historical interest, only.'' | ''Note: this is of historical interest, only.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 200 mg/m<sup>2</sup> IV once on day 15 | *[[Methotrexate (MTX)]] 200 mg/m<sup>2</sup> IV once on day 15 | ||
Line 468: | Line 462: | ||
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> PO once per day on days 1 to 5 | *[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[Sargramostim (Leukine)]] 5 mcg/kg SC once per day on days 4 to 13 (as needed) | *[[Sargramostim (Leukine)]] 5 mcg/kg SC once per day on days 4 to 13 (as needed) | ||
− | + | ====CNS therapy, prophylaxis==== | |
− | ====CNS prophylaxis==== | + | *[[Cytarabine (Ara-C)]] as follows: |
− | *[[Cytarabine (Ara-C)]] 50 mg IT once per day on days 1, 8, 15 | + | **Cycle 1: 50 mg IT once per day on days 1, 8, 15 |
− | + | **Cycle 2: 50 mg IT once on day 1 | |
'''21-day cycle for 2 cycles past complete remission (minimum of 4 cycles)''' | '''21-day cycle for 2 cycles past complete remission (minimum of 4 cycles)''' | ||
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#ee6b6e"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #2, "low-dose" #2 {{#subobject:d20b9a|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1001/jama.1991.03470010088036 Levine et al. 1991] |
+ | |1987-06 to 1988-11 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
|} | |} | ||
''Note: this is of historical interest, only; the MTX dose is slightly higher than above.'' | ''Note: this is of historical interest, only; the MTX dose is slightly higher than above.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 500 mg/m<sup>2</sup> IV once on day 15 | *[[Methotrexate (MTX)]] 500 mg/m<sup>2</sup> IV once on day 15 | ||
Line 494: | Line 492: | ||
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> PO once per day on days 1 to 5 | *[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Leucovorin (Folinic acid)]] |
− | *[[Folinic acid | + | ====CNS therapy, prophylaxis==== |
− | |||
− | ====CNS prophylaxis==== | ||
*[[Cytarabine (Ara-C)]] 50 mg IT once per day on days 1, 8, 21, 28 | *[[Cytarabine (Ara-C)]] 50 mg IT once per day on days 1, 8, 21, 28 | ||
− | |||
'''4 to 6 cycles''' | '''4 to 6 cycles''' | ||
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#ee6b6e"> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ===Regimen variant #3, "standard-dose" {{#subobject:8d9222|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199706053362304 Kaplan et al. 1997 (ACTG 142)] |
− | |style="background-color:#1a9851"|Phase | + | |1991-1994 |
− | |[[#m-BACOD| | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:#ffffbf"| | + | |[[#m-BACOD|m-BACOD]]; low-dose |
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
''Note: this is of historical interest, only.'' | ''Note: this is of historical interest, only.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] 200 mg/m<sup>2</sup> IV once on day 15 | *[[Methotrexate (MTX)]] 200 mg/m<sup>2</sup> IV once on day 15 | ||
Line 524: | Line 524: | ||
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 6 mg/m<sup>2</sup> PO once per day on days 1 to 5 | *[[Dexamethasone (Decadron)]] 6 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[Sargramostim (Leukine)]] 5 mcg/kg SC once per day on days 4 to 13 | *[[Sargramostim (Leukine)]] 5 mcg/kg SC once per day on days 4 to 13 | ||
− | + | ====CNS therapy, prophylaxis==== | |
− | ====CNS prophylaxis==== | + | *[[Cytarabine (Ara-C)]] as follows: |
− | *[[Cytarabine (Ara-C)]] 50 mg IT once per day on days 1, 8, 15 | + | **Cycle 1: 50 mg IT once per day on days 1, 8, 15 |
− | + | **Cycle 2: 50 mg IT once on day 1 | |
'''21-day cycle for 2 cycles past complete remission (minimum of 4 cycles)''' | '''21-day cycle for 2 cycles past complete remission (minimum of 4 cycles)''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Levine AM, Wernz JC, Kaplan L, Rodman N, Cohen P, Metroka C, Bennett JM, Rarick MU, Walsh C, Kahn J, Miles S, Ehmann WC, Feinberg J, Nathwani B, Gill PS, Mitsuyasu R. Low-dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance in AIDS-related lymphoma: a prospective multi-institutional trial. JAMA. 1991 Jul 3;266(1):84-8. [https:// | + | # Levine AM, Wernz JC, Kaplan L, Rodman N, Cohen P, Metroka C, Bennett JM, Rarick MU, Walsh C, Kahn J, Miles S, Ehmann WC, Feinberg J, Nathwani B, Gill PS, Mitsuyasu R. Low-dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance in AIDS-related lymphoma: a prospective multi-institutional trial. JAMA. 1991 Jul 3;266(1):84-8. [https://doi.org/10.1001/jama.1991.03470010088036 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/1710673/ PubMed] |
− | # Kaplan LD, Straus DJ, Testa MA, Von Roenn J, Dezube BJ, Cooley TP, Herndier B, Northfelt DW, Huang J, Tulpule A, Levine AM; National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. N Engl J Med. 1997 Jun 5;336(23):1641-8. [https:// | + | # '''ACTG 142:''' Kaplan LD, Straus DJ, Testa MA, Von Roenn J, Dezube BJ, Cooley TP, Herndier B, Northfelt DW, Huang J, Tulpule A, Levine AM; National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. N Engl J Med. 1997 Jun 5;336(23):1641-8. [https://doi.org/10.1056/NEJM199706053362304 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9171066/ PubMed] |
− | |||
==R-CDOP {{#subobject:ec091e|Regimen=1}}== | ==R-CDOP {{#subobject:ec091e|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
R-CDOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''oxil (Pegylated liposomal doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone | R-CDOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''oxil (Pegylated liposomal doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone | ||
<br>DR-COP: '''<u>D</u>'''oxil (pegylated liposomal doxorubicin), '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone | <br>DR-COP: '''<u>D</u>'''oxil (pegylated liposomal doxorubicin), '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:de2769|Variant=1}}=== | ===Regimen {{#subobject:de2769|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530691/ Levine et al. 2012 (AMC047)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530691/ Levine et al. 2012 (AMC047)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2007 to not reported |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Pegylated liposomal doxorubicin (Doxil)]] 40 mg/m<sup>2</sup> IV once on day 1 | *[[Pegylated liposomal doxorubicin (Doxil)]] 40 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5 | *[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5 | ||
+ | ====CNS therapy, prophylaxis==== | ||
*"CNS prophylaxis was mandated in patients with involvement of bone marrow, testis, sinuses, or epidural regions and with stage IV and/or at least two extranodal sites, with specific regimen left to physician discretion." | *"CNS prophylaxis was mandated in patients with involvement of bone marrow, testis, sinuses, or epidural regions and with stage IV and/or at least two extranodal sites, with specific regimen left to physician discretion." | ||
+ | ====Supportive therapy==== | ||
*Highly Active Antiretroviral Therapy (HAART) required; specific regimen left to physician discretion. Use of zidovudine was not allowed. | *Highly Active Antiretroviral Therapy (HAART) required; specific regimen left to physician discretion. Use of zidovudine was not allowed. | ||
− | |||
− | |||
*G-CSF prophylaxis, starting on day 3 and continuing until beyond nadir of blood counts, with one of the following: | *G-CSF prophylaxis, starting on day 3 and continuing until beyond nadir of blood counts, with one of the following: | ||
**[[Filgrastim (Neupogen)]] | **[[Filgrastim (Neupogen)]] | ||
Line 571: | Line 571: | ||
*Erythropoietin (e.g. [[Epoetin alfa (Procrit)]] or [[Darbepoetin alfa (Aranesp)]]) at physician discretion | *Erythropoietin (e.g. [[Epoetin alfa (Procrit)]] or [[Darbepoetin alfa (Aranesp)]]) at physician discretion | ||
*[[:Category:PCP_prophylaxis|PCP prophylaxis]] required | *[[:Category:PCP_prophylaxis|PCP prophylaxis]] required | ||
− | *Oral [[:Category:Fluoroquinolone|fluoroquinolone]] if CD4 cell count less than or equal to 100 and ANC less than 500/ | + | *Oral [[:Category:Fluoroquinolone|fluoroquinolone]] if CD4 cell count less than or equal to 100 and ANC less than 500/μL at entry or during treatment |
− | |||
'''21- to 28-day cycle for up to 6 cycles''' | '''21- to 28-day cycle for up to 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''AMC047:''' Levine AM, Noy A, Lee JY, Tam W, Ramos JC, Henry DH, Parekh S, Reid EG, Mitsuyasu R, Cooley T, Dezube BJ, Ratner L, Cesarman E, Tulpule A. Pegylated liposomal doxorubicin, rituximab, cyclophosphamide, vincristine, and prednisone in AIDS-related lymphoma: AIDS Malignancy Consortium study 047. J Clin Oncol. 2013 Jan 1;31(1):58-64. Epub 2012 Nov 19. [ | + | # '''AMC047:''' Levine AM, Noy A, Lee JY, Tam W, Ramos JC, Henry DH, Parekh S, Reid EG, Mitsuyasu R, Cooley T, Dezube BJ, Ratner L, Cesarman E, Tulpule A. Pegylated liposomal doxorubicin, rituximab, cyclophosphamide, vincristine, and prednisone in AIDS-related lymphoma: AIDS Malignancy Consortium study 047. J Clin Oncol. 2013 Jan 1;31(1):58-64. Epub 2012 Nov 19. [https://doi.org/10.1200/jco.2012.42.4648 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530691/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23169503/ PubMed] [https://clinicaltrials.gov/study/NCT00389818 NCT00389818] |
==R-CHOP {{#subobject:973922|Regimen=1}}== | ==R-CHOP {{#subobject:973922|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone | R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone | ||
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ===Regimen variant #1, 3 cycles {{#subobject:bbe63d|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ Kaplan et al. 2005 (AMC010)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ Kaplan et al. 2005 (AMC010)] | ||
− | |style="background-color:#1a9851"|Phase | + | |1998-2002 |
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
|[[#CHOP|CHOP]] | |[[#CHOP|CHOP]] | ||
− | |style="background-color:#ffffbf"| | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate |
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: This regimen variant was intended for patients with stage I, IE, or nonbulky stage II disease.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day -2 | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5 | *[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*Combination antiretrovirals were required | *Combination antiretrovirals were required | ||
− | *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 5 mcg/kg SC once per day from days 4 to 13 or until ANC greater than 10k/ | + | *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 5 mcg/kg SC once per day from days 4 to 13 or until ANC greater than 10k/μL. |
*PCP prophylaxis with ONE of the following: | *PCP prophylaxis with ONE of the following: | ||
− | **[[Trimethoprim | + | **[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] (dose/schedule not specified) |
**[[Dapsone (Aczone)]] (dose/schedule not specified) | **[[Dapsone (Aczone)]] (dose/schedule not specified) | ||
**[[Pentamidine (Nebupent)]] (dose/schedule not specified) | **[[Pentamidine (Nebupent)]] (dose/schedule not specified) | ||
− | |||
'''21-day cycle for 3 cycles for early disease, or minimum of 6 cycles or 2 past CR for advanced disease''' | '''21-day cycle for 3 cycles for early disease, or minimum of 6 cycles or 2 past CR for advanced disease''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Radiation_therapy|IFRT]] x | + | *[[#Radiation_therapy|IFRT]] consolidation x 4000 cGy |
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #2, prednisone 40 mg/m<sup>2</sup> {{#subobject:c5fd4a|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
− | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/jco.2005.05.4684 Boué et al. 2006] |
− | | | + | |Not reported |
− | + | |style="background-color:#91cf61"|Phase 2 | |
− | |style="background-color:# | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1111/j.1365-2141.2007.06943.x Ribera et al. 2007x] |
− | |style="background-color:#91cf61"|Phase | + | |2001-04 to 2006-04 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 | ||
+ | **In Boué et al. 2006, first dose was given on day -1 | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5 | *[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
− | + | ====CNS therapy, prophylaxis==== | |
− | ====CNS prophylaxis==== | + | *Ribera et al. 2007x: ''To be given with each cycle; day of administration not reported.'' |
− | ''To be given with each cycle; day of administration not reported.'' | ||
*[[Methotrexate (MTX)]] 12 mg IT | *[[Methotrexate (MTX)]] 12 mg IT | ||
*[[Cytarabine (Ara-C)]] 40 mg IT | *[[Cytarabine (Ara-C)]] 40 mg IT | ||
*[[Hydrocortisone (Cortef)]] 20 mg IT | *[[Hydrocortisone (Cortef)]] 20 mg IT | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*Combination antiretrovirals were required: one or two protease inhibitors and two nucleoside reverse transcriptase inhibitors | *Combination antiretrovirals were required: one or two protease inhibitors and two nucleoside reverse transcriptase inhibitors | ||
*PCP prophylaxis with ONE of the following: | *PCP prophylaxis with ONE of the following: | ||
− | **[[Trimethoprim | + | **[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] 160/800 mg PO TIW |
**[[Pentamidine (Nebupent)]] 300 mg inhaled (schedule not specified) | **[[Pentamidine (Nebupent)]] 300 mg inhaled (schedule not specified) | ||
− | |||
'''21-day cycle for 6 cycles''' | '''21-day cycle for 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *Ribera et al. 2007x, patients with bulky disease or a residual mass: [[#Radiation_therapy|IFRT]] consolidation (details not provided) |
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #3, prednisone 100 mg {{#subobject:b2deae|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ Kaplan et al. 2005 (AMC010)] |
− | |style="background-color:# | + | |1998-2002 |
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[#CHOP|CHOP]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: This regimen variant was intended for patients with advanced disease.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day -2 | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
− | |||
− | |||
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | ||
− | *[[Prednisone (Sterapred)]] | + | ====Glucocorticoid therapy==== |
− | + | *[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5 | |
− | + | ====Supportive therapy==== | |
− | + | *Combination antiretrovirals were required | |
− | + | *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 5 mcg/kg SC once per day from days 4 to 13 or until ANC greater than 10k/μL. | |
− | ====Supportive | + | *PCP prophylaxis with ONE of the following: |
− | * | + | **[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] (dose/schedule not specified) |
− | *PCP prophylaxis | + | **[[Dapsone (Aczone)]] (dose/schedule not specified) |
− | + | **[[Pentamidine (Nebupent)]] (dose/schedule not specified) | |
− | '''21-day cycle for 6 cycles''' | + | '''21-day cycle for a minimum of 6 cycles or 2 past CR''' |
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *AMC010, PR/CR: [[#Rituximab_monotherapy|Rituximab]] maintenance | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. [ | + | # '''AMC010:''' Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. [https://doi.org/10.1182/blood-2005-04-1437 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15914552/ PubMed] [https://clinicaltrials.gov/study/NCT00003595 NCT00003595] |
− | # Boué F, Gabarre J, Gisselbrecht C, Reynes J, Cheret A, Bonnet F, Billaud E, Raphael M, Lancar R, Costagliola D. Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin's lymphoma. J Clin Oncol. 2006 Sep 1;24(25):4123-8. Epub 2006 Aug 8. [ | + | # Boué F, Gabarre J, Gisselbrecht C, Reynes J, Cheret A, Bonnet F, Billaud E, Raphael M, Lancar R, Costagliola D. Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin's lymphoma. J Clin Oncol. 2006 Sep 1;24(25):4123-8. Epub 2006 Aug 8. [https://doi.org/10.1200/jco.2005.05.4684 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16896005/ PubMed] |
− | # Ribera JM, Oriol A, Morgades M, González-Barca E, Miralles P, López-Guillermo A, Gardella S, López A, Abella E, García M; PETHEMA | + | # Ribera JM, Oriol A, Morgades M, González-Barca E, Miralles P, López-Guillermo A, Gardella S, López A, Abella E, García M; PETHEMA; GELTAMO; GELCAB; GESIDA. Safety and efficacy of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab in patients with human immunodeficiency virus-associated diffuse large B-cell lymphoma: results of a phase II trial. Br J Haematol. 2008 Feb;140(4):411-9. Epub 2007 Dec 19. [https://doi.org/10.1111/j.1365-2141.2007.06943.x link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18162120/ PubMed] |
− | |||
==R-CODOX-M {{#subobject:2c9b53|Regimen=1}}== | ==R-CODOX-M {{#subobject:2c9b53|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
R-CODOX-M: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate | R-CODOX-M: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:b34341|Variant=1}}=== | ===Regimen {{#subobject:b34341|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497960/ Noy et al. 2015 (AMC 048)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497960/ Noy et al. 2015 (AMC 048)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2007-2010 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: This regimen was intended for '''low-risk''' HIV-associated Burkitt lymphoma, and was the first published prospective regimen to explicitly use rituximab. This is sometimes called modified Magrath but is in fact a second modification to the modified Magrath described by [https://doi.org/10.1080/1042819031000141301 LaCasce et al. 2004].'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
+ | ====Targeted therapy==== | ||
+ | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once per day on days 1 & 2 | *[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once per day on days 1 & 2 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8 | ||
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once on day 15 | *[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once on day 15 | ||
− | + | ====CNS therapy, prophylaxis==== | |
− | ====CNS prophylaxis==== | ||
*[[Cytarabine (Ara-C)]] 50 mg IT once on day 1 | *[[Cytarabine (Ara-C)]] 50 mg IT once on day 1 | ||
*[[Methotrexate (MTX)]] 12 mg IT once on day 1 | *[[Methotrexate (MTX)]] 12 mg IT once on day 1 | ||
*[[Hydrocortisone (Cortef)]] 50 mg IT once on day 1 | *[[Hydrocortisone (Cortef)]] 50 mg IT once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV once 24 hours after methotrexate, then 25 mg/m<sup>2</sup> IV every 6 hours until methotrexate level is less than 50 nmol/L |
− | *[[Folinic acid | ||
− | |||
− | |||
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 3 | *[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 3 | ||
− | *[[Filgrastim (Neupogen)]] (dose not specified) SC once per day, starting once methotrexate level is less than 50 nmol/L (approximately day 18) and continuing until ANC greater than 1000/ | + | *[[Filgrastim (Neupogen)]] (dose not specified) SC once per day, starting once methotrexate level is less than 50 nmol/L (approximately day 18) and continuing until ANC greater than 1000/μL |
− | |||
'''21- to 28-day cycle for 3 cycles''' | '''21- to 28-day cycle for 3 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Lacasce A, Howard O, Lib S, Fisher D, Weng A, Neuberg D, Shipp M. Modified Magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma. 2004 Apr;45(4):761-7. [https:// | + | # Lacasce A, Howard O, Lib S, Fisher D, Weng A, Neuberg D, Shipp M. Modified Magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma. 2004 Apr;45(4):761-7. [https://doi.org/10.1080/1042819031000141301 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15160953/ PubMed] |
− | # '''Retrospective:''' Barnes JA, Lacasce AS, Feng Y, Toomey CE, Neuberg D, Michaelson JS, Hochberg EP, Abramson JS. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: a retrospective analysis. Ann Oncol. 2011 Aug;22(8):1859-64. Epub 2011 Feb 21. [ | + | # '''Retrospective:''' Barnes JA, Lacasce AS, Feng Y, Toomey CE, Neuberg D, Michaelson JS, Hochberg EP, Abramson JS. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: a retrospective analysis. Ann Oncol. 2011 Aug;22(8):1859-64. Epub 2011 Feb 21. [https://doi.org/10.1093/annonc/mdq677 link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/21339382/ PubMed] content property of [https://hemonc.org HemOnc.org] |
− | # '''Retrospective:''' Kassam S, Bower M, Lee SM, de Vos J, Fields P, Gandhi S, Nelson M, Montoto S, Tenant-Flowers M, Burns F, Marcus R, Edwards SG, Cwynarski K. A retrospective, multi-center analysis of treatment intensification for HIV-positive patients with high-risk diffuse large B-cell lymphoma. Leuk Lymphoma. 2013 Sep;54(9):1921-7. Epub 2013 Jan 4. [https:// | + | # '''Retrospective:''' Kassam S, Bower M, Lee SM, de Vos J, Fields P, Gandhi S, Nelson M, Montoto S, Tenant-Flowers M, Burns F, Marcus R, Edwards SG, Cwynarski K. A retrospective, multi-center analysis of treatment intensification for HIV-positive patients with high-risk diffuse large B-cell lymphoma. Leuk Lymphoma. 2013 Sep;54(9):1921-7. Epub 2013 Jan 4. [https://doi.org/10.3109/10428194.2012.754024 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23206228/ PubMed] |
− | # Noy A, Lee JY, Cesarman E, Ambinder R, Baiocchi R, Reid E, Ratner L, Wagner-Johnston N, Kaplan L. AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Blood. 2015 Jul 9;126(2):160-6. Epub 2015 May 8. [ | + | # '''AMC 048:''' Noy A, Lee JY, Cesarman E, Ambinder R, Baiocchi R, Reid E, Ratner L, Wagner-Johnston N, Kaplan L. AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Blood. 2015 Jul 9;126(2):160-6. Epub 2015 May 8. [https://doi.org/10.1182/blood-2015-01-623900 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497960/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25957391/ PubMed] [https://clinicaltrials.gov/study/NCT00392834 NCT00392834] |
− | |||
==R-CODOX-M/R-IVAC {{#subobject:9268b2|Regimen=1}}== | ==R-CODOX-M/R-IVAC {{#subobject:9268b2|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
R-CODOX-M/R-IVAC: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate alternating with '''<u>R</u>'''ituximab, '''<u>I</u>'''fosfamide, '''<u>V</u>'''epesid (Etoposide), '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | R-CODOX-M/R-IVAC: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate alternating with '''<u>R</u>'''ituximab, '''<u>I</u>'''fosfamide, '''<u>V</u>'''epesid (Etoposide), '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:7a0131|Variant=1}}=== | ===Regimen {{#subobject:7a0131|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1080/1042819031000141301 LaCasce et al. 2004] |
− | | style="background-color:#ffffbe" |Phase | + | |Not reported |
+ | | style="background-color:#ffffbe" |Phase 2, fewer than 20 pts | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497960/ Noy et al. 2015 (AMC 048)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497960/ Noy et al. 2015 (AMC 048)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2007-2010 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: This protocol was intended for '''high-risk''' HIV-associated Burkitt lymphoma, and was the first published prospective regimen to explicitly use rituximab. This is sometimes called modified Magrath but is in fact a second modification to the modified Magrath described in LaCasce et al. 2004. Note that the preferred sequence is A, B, A, B but the authors note that for patients with anasarca or other concerns for retaining MTX, the sequence can be B, A, B, A. Also note that the paper does not specify whether hydrocortisone is used with the day 3 IT chemo; the authors have clarified (December 31, 2017) that this is left to institutional policy.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ==== | + | ====Targeted therapy, both portions (cycles 1 to 4)==== |
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Chemotherapy, R-CODOX-M portion (cycles 1 & 3; "Part A")==== | ||
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once per day on days 1 & 2 | *[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once per day on days 1 & 2 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8 | ||
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once on day 15 | *[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once on day 15 | ||
− | + | ====Supportive therapy, R-CODOX-M portion (cycles 1 & 3; "Part A")==== | |
− | ====CNS prophylaxis==== | + | *[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV once 24 hours after methotrexate, then 25 mg/m<sup>2</sup> IV every 6 hours until methotrexate level is less than 50 nmol/L |
+ | *[[Filgrastim (Neupogen)]] (dose not specified) SC once per day, starting once methotrexate level is less than 50 nmol/L (approximately day 18) and continuing until ANC greater than 1000/μL | ||
+ | ====CNS prophylaxis, R-CODOX-M portion (cycles 1 & 3; "Part A")==== | ||
*[[Cytarabine (Ara-C)]] 50 mg IT once per day on days 1 & 3 | *[[Cytarabine (Ara-C)]] 50 mg IT once per day on days 1 & 3 | ||
*[[Methotrexate (MTX)]] 12 mg IT once on day 1 | *[[Methotrexate (MTX)]] 12 mg IT once on day 1 | ||
*[[Hydrocortisone (Cortef)]] 50 mg IT once on day 1 | *[[Hydrocortisone (Cortef)]] 50 mg IT once on day 1 | ||
− | + | ====Chemotherapy, R-IVAC portion (cycles 2 & 4; "Part B")==== | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | ====Chemotherapy, | ||
− | |||
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 7500 mg/m<sup>2</sup>) | *[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 7500 mg/m<sup>2</sup>) | ||
*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 300 mg/m<sup>2</sup>) | *[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 300 mg/m<sup>2</sup>) | ||
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>) | ||
− | + | ====Supportive therapy, R-IVAC portion (cycles 2 & 4; "Part B")==== | |
− | ==== | ||
− | |||
− | |||
− | |||
*[[Mesna (Mesnex)]] 1500 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 7500 mg/m<sup>2</sup>) | *[[Mesna (Mesnex)]] 1500 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 7500 mg/m<sup>2</sup>) | ||
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 6 | *[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 6 | ||
− | + | ====CNS prophylaxis, R-IVAC portion (cycles 2 & 4; "Part B")==== | |
− | '''4 | + | *[[Methotrexate (MTX)]] 12 mg IT once on day 5 |
− | + | '''4 cycles (see note)''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Lacasce A, Howard O, Lib S, Fisher D, Weng A, Neuberg D, Shipp M. Modified Magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma. 2004 Apr;45(4):761-7. [https:// | + | # Lacasce A, Howard O, Lib S, Fisher D, Weng A, Neuberg D, Shipp M. Modified Magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma. 2004 Apr;45(4):761-7. [https://doi.org/10.1080/1042819031000141301 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15160953/ PubMed] |
− | # '''Retrospective:''' Barnes JA, Lacasce AS, Feng Y, Toomey CE, Neuberg D, Michaelson JS, Hochberg EP, Abramson JS. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: a retrospective analysis. Ann Oncol. 2011 Aug;22(8):1859-64. Epub 2011 Feb 21. [ | + | # '''Retrospective:''' Barnes JA, Lacasce AS, Feng Y, Toomey CE, Neuberg D, Michaelson JS, Hochberg EP, Abramson JS. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: a retrospective analysis. Ann Oncol. 2011 Aug;22(8):1859-64. Epub 2011 Feb 21. [https://doi.org/10.1093/annonc/mdq677 link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/21339382/ PubMed] content property of [https://hemonc.org HemOnc.org] |
− | # '''Retrospective:''' Kassam S, Bower M, Lee SM, de Vos J, Fields P, Gandhi S, Nelson M, Montoto S, Tenant-Flowers M, Burns F, Marcus R, Edwards SG, Cwynarski K. A retrospective, multi-center analysis of treatment intensification for HIV-positive patients with high-risk diffuse large B-cell lymphoma. Leuk Lymphoma. 2013 Sep;54(9):1921-7. Epub 2013 Jan 4. [https:// | + | # '''Retrospective:''' Kassam S, Bower M, Lee SM, de Vos J, Fields P, Gandhi S, Nelson M, Montoto S, Tenant-Flowers M, Burns F, Marcus R, Edwards SG, Cwynarski K. A retrospective, multi-center analysis of treatment intensification for HIV-positive patients with high-risk diffuse large B-cell lymphoma. Leuk Lymphoma. 2013 Sep;54(9):1921-7. Epub 2013 Jan 4. [https://doi.org/10.3109/10428194.2012.754024 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23206228/ PubMed] |
− | # Noy A, Lee JY, Cesarman E, Ambinder R, Baiocchi R, Reid E, Ratner L, Wagner-Johnston N, Kaplan L. AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Blood. 2015 Jul 9;126(2):160-6. Epub 2015 May 8. [ | + | # '''AMC 048:''' Noy A, Lee JY, Cesarman E, Ambinder R, Baiocchi R, Reid E, Ratner L, Wagner-Johnston N, Kaplan L. AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Blood. 2015 Jul 9;126(2):160-6. Epub 2015 May 8. [https://doi.org/10.1182/blood-2015-01-623900 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497960/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25957391/ PubMed] [https://clinicaltrials.gov/study/NCT00392834 NCT00392834] |
==R-EPOCH, dose-escalated {{#subobject:3c32e1|Regimen=1}}== | ==R-EPOCH, dose-escalated {{#subobject:3c32e1|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
R-EPOCH: '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin (Vincristine), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin) | R-EPOCH: '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin (Vincristine), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:e2d121|Variant=1}}=== | ===Regimen {{#subobject:e2d121|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858478/ Sparano et al. 2010 (AMC034)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858478/ Sparano et al. 2010 (AMC034)] | ||
− | |style="background-color:#1a9851"|Randomized Phase | + | |2002-2006 |
− | |EPOCH, then R | + | |style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ic) |
− | |style="background-color:# | + | |[[#EPOCH_888|EPOCH]], then [[#Rituximab_monotherapy_888|R]] |
+ | |style="background-color:#d3d3d3"|Not reported<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>While this was a randomized trial, the primary efficacy endpoint was a historical control; see article for details.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once (day not specified), '''given first''' | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m<sup>2</sup>) | *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m<sup>2</sup>) | ||
− | |||
*[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m<sup>2</sup>) | *[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m<sup>2</sup>) | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] by the following laboratory-based criteria: |
− | **CD4+ count less than 100/ | + | **CD4+ count less than 100/μL: 187 mg/m<sup>2</sup> IV over 15 minutes once on day 5 |
− | **CD4+ count | + | **CD4+ count more than 100/μL: 375 mg/m<sup>2</sup> IV over 15 minutes once on day 5 |
− | |||
*[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>) | *[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>) | ||
− | + | ====Glucocorticoid therapy==== | |
− | ====Supportive | + | *[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 5 |
+ | ====Supportive therapy==== | ||
*EITHER [[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting 24 hours after EPOCH is completed and continuing until "neutrophil recovery"—no absolute count specified | *EITHER [[Filgrastim (Neupogen)]] 5 mcg/kg SC 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 once 24 hours after EPOCH is completed | *OR [[Pegfilgrastim (Neulasta)]] 6 mg SC once 24 hours after EPOCH is completed | ||
− | *[[Trimethoprim | + | *[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO TIW (e.g. Monday, Wednesday, Friday) |
*[[Fluconazole (Diflucan)]] 100 mg PO once per day | *[[Fluconazole (Diflucan)]] 100 mg PO once per day | ||
*[[Ciprofloxacin (Cipro)]] 500 mg PO twice per day, starting on day 8 and to continue to at least day 15 or postnadir ANC of at least 1000 | *[[Ciprofloxacin (Cipro)]] 500 mg PO twice per day, 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 | **Other fluoroquinolone can be used at discretion of physician | ||
− | |||
'''21-day cycle for 6 to 8 cycles''' | '''21-day cycle for 6 to 8 cycles''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | **In each subsequent cycle, increase cyclophosphamide dose by 187 mg/m<sup>2</sup> if the neutrophil nadir is greater than 500/μL and platelet nadir is greater than 25 x 10<sup>9</sup>/L. Decrease dose by 187 mg/m<sup>2</sup> if the neutrophil nadir is less than 500/μL or platelet nadir is less than 25 x 10<sup>9</sup>/L. | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Sparano JA, Lee JY, Kaplan LD, Levine AM, Ramos JC, Ambinder RF, Wachsman W, Aboulafia D, Noy A, Henry DH, Von Roenn J, Dezube BJ, Remick SC, Shah MH, Leichman L, Ratner L, Cesarman E, Chadburn A, Mitsuyasu R; AIDS Malignancy Consortium. Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma. Blood. 2010 Apr 15;115(15):3008-16. Epub 2009 Dec 18. [ | + | # '''AMC034:''' Sparano JA, Lee JY, Kaplan LD, Levine AM, Ramos JC, Ambinder RF, Wachsman W, Aboulafia D, Noy A, Henry DH, Von Roenn J, Dezube BJ, Remick SC, Shah MH, Leichman L, Ratner L, Cesarman E, Chadburn A, Mitsuyasu R; AIDS Malignancy Consortium. Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma. Blood. 2010 Apr 15;115(15):3008-16. Epub 2009 Dec 18. [https://doi.org/10.1182/blood-2009-08-231613 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858478/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20023215/ PubMed] [https://clinicaltrials.gov/study/NCT00049036 NCT00049036] |
− | |||
==SC-EPOCH-RR {{#subobject:8d6ea0|Regimen=1}}== | ==SC-EPOCH-RR {{#subobject:8d6ea0|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
SC-EPOCH-RR: '''<u>S</u>'''hort '''<u>C</u>'''ourse '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, with dose-dense '''<u>R</u>'''ituximab | SC-EPOCH-RR: '''<u>S</u>'''hort '''<u>C</u>'''ourse '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, with dose-dense '''<u>R</u>'''ituximab | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:ae5234|Variant=1}}=== | ===Regimen {{#subobject:ae5234|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901044/ Dunleavy et al. 2013 (NCI 93-C-0133<sub>HIV</sub>)] |
− | |style="background-color:# | + | |2000-11 to 2009-12 |
+ | |style="background-color:#ffffbe"|Phase 2, fewer than 20 pts in this arm | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858473/ Dunleavy et al. 2010 (NCI 97-C-0040)] |
− | |style="background-color:# | + | |2001-06 to 2009-04 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | + | ''Note: NCI 97-C-0040 reported on HIV+ DLBCL patients, whereas NCI 93-C-0133 reported on HIV+ Burkitt lymphoma patients. The regimen is the same.'' | |
− | '' | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Targeted therapy==== | ||
+ | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 & 5 | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m<sup>2</sup>) | *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m<sup>2</sup>) | ||
− | |||
*[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m<sup>2</sup>) | *[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m<sup>2</sup>) | ||
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 2 hours once on day 5 | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 2 hours once on day 5 | ||
*[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>) | *[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>) | ||
− | + | ====Glucocorticoid therapy==== | |
− | ====CNS prophylaxis==== | + | *[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 5 |
− | *[[Methotrexate (MTX)]] 12 mg IT once per day on days 1 & 5 | + | ====CNS therapy, prophylaxis==== |
− | + | *[[Methotrexate (MTX)]] as follows: | |
− | ====Supportive | + | **Cycles 3 to 5: 12 mg IT once per day on days 1 & 5 |
− | *[[Filgrastim (Neupogen)]] 300 mcg SC once per day, starting on day 6, continue until ANC greater than 5k/ | + | ====Supportive therapy==== |
− | *[[Trimethoprim | + | *[[Filgrastim (Neupogen)]] 300 mcg SC once per day, starting on day 6, continue until ANC greater than 5k/μL above nadir |
+ | *[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO TIW (e.g. Monday, Wednesday, Friday) | ||
*[[Omeprazole (Prilosec)]] 20 mg PO once per day (or equivalent) | *[[Omeprazole (Prilosec)]] 20 mg PO once per day (or equivalent) | ||
*[[Docusate (Colace)]] and [[Sennosides (Senna)]] 2 tablets PO twice per day as necessary for constipation | *[[Docusate (Colace)]] and [[Sennosides (Senna)]] 2 tablets PO twice per day as necessary for constipation | ||
*[[Lactulose]] 20 gms PO every 6 hours as necessary for constipation. | *[[Lactulose]] 20 gms PO every 6 hours as necessary for constipation. | ||
− | |||
'''21-day cycle for 3 to 6 cycles, one cycle beyond CR''' | '''21-day cycle for 3 to 6 cycles, one cycle beyond CR''' | ||
− | + | </div> | |
− | ====Dose modifications==== | + | <div class="toccolours" style="background-color:#fff2ae"> |
+ | ====Dose and schedule modifications==== | ||
*[[Cyclophosphamide (Cytoxan)]]: | *[[Cyclophosphamide (Cytoxan)]]: | ||
− | **In the subsequent cycle, decrease dose by 187 mg/m<sup>2</sup> if ANC was less than 500/ | + | **In the subsequent cycle, decrease dose by 187 mg/m<sup>2</sup> if ANC was less than 500/μL for 2 to 4 days or platelets were less than 25 x 10<sup>9</sup>/L for 2 to 4 days. |
− | **In the subsequent cycle, decrease dose by 375 mg/m<sup>2</sup> if ANC was less than 500/ | + | **In the subsequent cycle, decrease dose by 375 mg/m<sup>2</sup> if ANC was less than 500/μL for 5 or more days or platelets were less than 25 x 10<sup>9</sup>/L for 5 or more days. |
− | **If dose-reduced in prior cycle, increase dose by 187 mg/m<sup>2</sup>, up to maximum of 750 mg/m<sup>2</sup>, if ANC was greater than 500/ | + | **If dose-reduced in prior cycle, increase dose by 187 mg/m<sup>2</sup>, up to maximum of 750 mg/m<sup>2</sup>, if ANC was greater than 500/μL and platelets were greater than 25 x 10<sup>9</sup>/L for the entire cycle. |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Dunleavy K, Little RF, Pittaluga S, Grant N, Wayne AS, Carrasquillo JA, Steinberg SM, Yarchoan R, Jaffe ES, Wilson WH. The role of tumor histogenesis, FDG-PET, and short-course EPOCH with dose-dense rituximab (SC-EPOCH-RR) in HIV-associated diffuse large B-cell lymphoma. Blood. 2010 Apr 15;115(15):3017-24. Epub 2010 Feb 3. [ | + | # '''NCI 97-C-0040:''' Dunleavy K, Little RF, Pittaluga S, Grant N, Wayne AS, Carrasquillo JA, Steinberg SM, Yarchoan R, Jaffe ES, Wilson WH. The role of tumor histogenesis, FDG-PET, and short-course EPOCH with dose-dense rituximab (SC-EPOCH-RR) in HIV-associated diffuse large B-cell lymphoma. Blood. 2010 Apr 15;115(15):3017-24. Epub 2010 Feb 3. [https://doi.org/10.1182/blood-2009-11-253039 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858473/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20130244/ PubMed] [https://clinicaltrials.gov/study/NCT00001563 NCT00001563] |
− | # Dunleavy K, Pittaluga S, Shovlin M, Steinberg SM, Cole D, Grant C, Widemann B, Staudt LM, Jaffe ES, Little RF, Wilson WH. Low-intensity therapy in adults with Burkitt's lymphoma. N Engl J Med. 2013 Nov 14;369(20):1915-25. [https:// | + | # '''NCI 93-C-0133<sub>HIV</sub>:''' Dunleavy K, Pittaluga S, Shovlin M, Steinberg SM, Cole D, Grant C, Widemann B, Staudt LM, Jaffe ES, Little RF, Wilson WH. Low-intensity therapy in adults with Burkitt's lymphoma. N Engl J Med. 2013 Nov 14;369(20):1915-25. [https://doi.org/10.1056/NEJMoa1308392 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24224624/ PubMed] [https://clinicaltrials.gov/study/NCT00001337 NCT00001337] |
==Stanford V {{#subobject:c00372|Regimen=1}}== | ==Stanford V {{#subobject:c00372|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:19ebaa|Variant=1}}=== | ===Regimen {{#subobject:19ebaa|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2002-03-0989 Spina et al. 2002] |
− | |style="background-color:#91cf61"|Phase | + | |1997-05 to 2001-10 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
''Note: this regimen was for HIV-associated Hodgkin lymphoma, unfavorable stage I or advanced stage.'' | ''Note: this regimen was for HIV-associated Hodgkin lymphoma, unfavorable stage I or advanced stage.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per week on weeks 1, 3, 5, 7, 9, 11 | *[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per week on weeks 1, 3, 5, 7, 9, 11 | ||
Line 936: | Line 911: | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per week on weeks 2, 4, 6, 8, 10, 12 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per week on weeks 2, 4, 6, 8, 10, 12 | ||
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV once per week on weeks 2, 4, 6, 8, 10, 12 | *[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV once per week on weeks 2, 4, 6, 8, 10, 12 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] as follows: | *[[Prednisone (Sterapred)]] as follows: | ||
**Weeks 1 to 10: 40 mg/m<sup>2</sup> PO every other day | **Weeks 1 to 10: 40 mg/m<sup>2</sup> PO every other day | ||
**Weeks 11 & 12: taper by 10 mg/m<sup>2</sup> every other day until off | **Weeks 11 & 12: taper by 10 mg/m<sup>2</sup> every other day until off | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 3 to 7, 9 to 13, 17 to 21, 23 to 26 | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 3 to 7, 9 to 13, 17 to 21, 23 to 26 | ||
− | *[[Trimethoprim | + | *[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO once per day throughout the course of treatment |
*[[Fluconazole (Diflucan)]] 100 mg PO once per day throughout the course of treatment | *[[Fluconazole (Diflucan)]] 100 mg PO once per day throughout the course of treatment | ||
− | |||
'''12-week course''' | '''12-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *PR: [[#Radiation_therapy|IFRT]] x | + | *Spina et al. 2002, PR: [[#Radiation_therapy|IFRT]] consolidation x 3600 cGy |
− | *CR with initial bulky disease (5 cm or larger): [[#Radiation_therapy|IFRT]] x | + | *Spina et al. 2002, CR with initial bulky disease (5 cm or larger): [[#Radiation_therapy|IFRT]] consolidation x 3600 cGy |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Spina M, Gabarre J, Rossi G, Fasan M, Schiantarelli C, Nigra E, Mena M, Antinori A, Ammassari A, Talamini R, Vaccher E, di Gennaro G, Tirelli U. Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection. Blood. 2002 Sep 15;100(6):1984-8. [ | + | # Spina M, Gabarre J, Rossi G, Fasan M, Schiantarelli C, Nigra E, Mena M, Antinori A, Ammassari A, Talamini R, Vaccher E, di Gennaro G, Tirelli U. Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection. Blood. 2002 Sep 15;100(6):1984-8. [https://doi.org/10.1182/blood-2002-03-0989 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12200356/ PubMed] |
− | =Consolidation | + | =Consolidation after upfront therapy= |
==Radiation therapy {{#subobject:3e41de|Regimen=1}}== | ==Radiation therapy {{#subobject:3e41de|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
IFRT: '''<u>I</u>'''nvolved '''<u>F</u>'''ield '''<u>R</u>'''adiation '''<u>T</u>'''herapy | IFRT: '''<u>I</u>'''nvolved '''<u>F</u>'''ield '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #1, 3600 cGy of IFRT {{#subobject:7f22e5|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2002-03-0989 Spina et al. 2002] |
− | |style="background-color:#91cf61"|Phase | + | |1997-05 to 2001-10 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Stanford_V|Stanford V]] x 12 wk | + | *[[#Stanford_V|Stanford V]] induction x 12 wk |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External beam radiotherapy]] | + | *[[External beam radiotherapy]] 3600 cGy in 200 cGy fractions, 5 days per week |
− | |||
'''4-week course''' | '''4-week course''' | ||
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #2, 4000 cGy of IFRT {{#subobject:029c6c|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ Kaplan et al. 2005 (AMC010)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ Kaplan et al. 2005 (AMC010)] | ||
− | |style="background-color:#91cf61"|Non-randomized | + | |1998-2002 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: This regimen variant was intended for patients with stage I, IE, or nonbulky stage II disease.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#R-CHOP|R-CHOP]] x 3 | + | *Induction [[#R-CHOP|R-CHOP]] x 3 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External beam radiotherapy]] to a total dose of at least | + | *[[External beam radiotherapy]] to a total dose of at least 4000 cGy |
− | |||
'''One course''' | '''One course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *PR/CR: [[#Rituximab_monotherapy|Rituximab | + | *AMC010, PR/CR: [[#Rituximab_monotherapy|Rituximab]] maintenance |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Spina M, Gabarre J, Rossi G, Fasan M, Schiantarelli C, Nigra E, Mena M, Antinori A, Ammassari A, Talamini R, Vaccher E, di Gennaro G, Tirelli U. Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection. Blood. 2002 Sep 15;100(6):1984-8. [ | + | # Spina M, Gabarre J, Rossi G, Fasan M, Schiantarelli C, Nigra E, Mena M, Antinori A, Ammassari A, Talamini R, Vaccher E, di Gennaro G, Tirelli U. Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection. Blood. 2002 Sep 15;100(6):1984-8. [https://doi.org/10.1182/blood-2002-03-0989 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12200356/ PubMed] |
− | # '''AMC010:''' Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. [ | + | # '''AMC010:''' Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. [https://doi.org/10.1182/blood-2005-04-1437 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15914552/ PubMed] [https://clinicaltrials.gov/study/NCT00003595 NCT00003595] |
− | |||
==Rituximab monotherapy {{#subobject:d2786f|Regimen=1}}== | ==Rituximab monotherapy {{#subobject:d2786f|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:e49f13|Variant=1}}=== | ===Regimen {{#subobject:e49f13|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ Kaplan et al. 2005 (AMC010)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ Kaplan et al. 2005 (AMC010)] | ||
− | |style="background-color:#91cf61"|Non-randomized | + | |1998-2002 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | * | + | *AMC010, early disease: Definitive [[#Radiation_therapy|IFRT]] |
− | * | + | *AMC010, advanced disease: Induction [[#R-CHOP|R-CHOP]] |
− | ==== | + | </div> |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''1-month cycle for 3 cycles''' | '''1-month cycle for 3 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. [ | + | # '''AMC010:''' Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. [https://doi.org/10.1182/blood-2005-04-1437 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15914552/ PubMed] [https://clinicaltrials.gov/study/NCT00003595 NCT00003595] |
− | |||
=Consolidation after salvage therapy= | =Consolidation after salvage therapy= | ||
− | |||
==BEAM, then auto HSCT {{#subobject:f357b4|Regimen=1}}== | ==BEAM, then auto HSCT {{#subobject:f357b4|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
BEAM: '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | BEAM: '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:9a79af|Variant=1}}=== | ===Regimen {{#subobject:9a79af|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 80%; text-align:center;" |
− | !style="width: | + | !style="width: 25%"|Study |
− | !style="width: | + | !style="width: 25%"|Dates of enrollment |
− | !style="width: | + | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2003.06.039 Re et al. 2003] |
− | |style="background-color:#91cf61"|Phase | + | |2000-09 to 2003-04 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
| | | | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000843/ Alvarnas et al. 2016 (BMT CTN 0803/AMC 071)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000843/ Alvarnas et al. 2016 (BMT CTN 0803/AMC 071)] | ||
− | |style="background-color:#91cf61"|Phase | + | |2010-04 to 2013-03 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|1-year OS: 87% (95% CI, 72-94.5) | |1-year OS: 87% (95% CI, 72-94.5) | ||
|- | |- | ||
|} | |} | ||
''Note: days of chemotherapy are slightly different in Re et al. 2003; see paper for details.'' | ''Note: days of chemotherapy are slightly different in Re et al. 2003; see paper for details.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -6 | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -6 | ||
− | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV every 12 hours on days -5 to -2 ( | + | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV every 12 hours on days -5 to -2 (total dose: 800 mg/m<sup>2</sup>) |
− | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days -5 to -2 ( | + | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days -5 to -2 (total dose: 800 mg/m<sup>2</sup>) |
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -1 | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -1 | ||
− | |||
'''Hematopoietic stem cells are reinfused on day 0''' | '''Hematopoietic stem cells are reinfused on day 0''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Re A, Cattaneo C, Michieli M, Casari S, Spina M, Rupolo M, Allione B, Nosari A, Schiantarelli C, Vigano M, Izzi I, Ferremi P, Lanfranchi A, Mazzuccato M, Carosi G, Tirelli U, Rossi G. High-dose therapy and autologous peripheral-blood stem-cell transplantation as salvage treatment for HIV-associated lymphoma in patients receiving highly active antiretroviral therapy. J Clin Oncol. 2003 Dec 1;21(23):4423-7. Epub 2003 Oct 27. | + | # Re A, Cattaneo C, Michieli M, Casari S, Spina M, Rupolo M, Allione B, Nosari A, Schiantarelli C, Vigano M, Izzi I, Ferremi P, Lanfranchi A, Mazzuccato M, Carosi G, Tirelli U, Rossi G. High-dose therapy and autologous peripheral-blood stem-cell transplantation as salvage treatment for HIV-associated lymphoma in patients receiving highly active antiretroviral therapy. J Clin Oncol. 2003 Dec 1;21(23):4423-7. Epub 2003 Oct 27. [https://doi.org/10.1200/jco.2003.06.039 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14581441/ PubMed] |
− | # Alvarnas JC, Le Rademacher J, Wang Y, Little RF, Akpek G, Ayala E, Devine S, Baiocchi R, Lozanski G, Kaplan L, Noy A, Popat U, Hsu J, Morris LE Jr, Thompson J, Horowitz MM, Mendizabal A, Levine A, Krishnan A, Forman SJ, Navarro WH, Ambinder R. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial. Blood. 2016 Aug 25;128(8):1050-8. Epub 2016 Jun 13. [ | + | # '''BMT CTN 0803/AMC 071:''' Alvarnas JC, Le Rademacher J, Wang Y, Little RF, Akpek G, Ayala E, Devine S, Baiocchi R, Lozanski G, Kaplan L, Noy A, Popat U, Hsu J, Morris LE Jr, Thompson J, Horowitz MM, Mendizabal A, Levine A, Krishnan A, Forman SJ, Navarro WH, Ambinder R. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial. Blood. 2016 Aug 25;128(8):1050-8. Epub 2016 Jun 13. [https://doi.org/10.1182/blood-2015-08-664706 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000843/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27297790/ PubMed] [https://clinicaltrials.gov/study/NCT01141712 NCT01141712] |
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[[Category:HIV-associated lymphoma regimens]] | [[Category:HIV-associated lymphoma regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Aggressive lymphomas]] | [[Category:Aggressive lymphomas]] |
Latest revision as of 23:41, 15 July 2024
Section editor | |
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Tarsheen Sethi, MD, MSCI Yale University New Haven, CT, USA |
19 regimens on this page
25 variants on this page
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The most common HIV-associated lymphomas are of DLBCL or Burkitt lymphoma histology; plasmablastic lymphoma and primary effusion lymphomas are also frequently seen in advanced-stage HIV/AIDS. In patients with a normal CD4+ T-cell count and well-controlled HIV, the lymphoma is typically treated as per the histologic subtype. For others, regimens specific to HIV-associated lymphoma have been developed and are included here.
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - B-cell Lymphomas.
Untreated, pre-phase
CVP
CVP: Cyclophosphamide, Vincristine, Prednisone
COP: Cyclophosphamide, Oncovin (Vincristine), Prednisone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Galicier et al. 2007 (LMB86) | 1992-11 to 2006-01 | Phase 2 |
Chemotherapy
- Cyclophosphamide (Cytoxan) 300 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2/day IV or PO on days 1 to 7
7-day course
Subsequent treatment
- COPADM induction
References
- LMB86: Galicier L, Fieschi C, Borie R, Meignin V, Daniel MT, Gérard L, Oksenhendler E. Intensive chemotherapy regimen (LMB86) for St Jude stage IV AIDS-related Burkitt lymphoma/leukemia: a prospective study. Blood. 2007 Oct 15;110(8):2846-54. Epub 2007 Jul 3. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Upfront therapy
CHOP
CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
CHOP-21: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone every 21 days
ACOP
CAVP
COPA
VACP
VCAP
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kaplan et al. 2005 (AMC010) | 1998-2002 | Phase 3 (C) | R-CHOP | Did not meet primary endpoint of CR rate |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive therapy
- Combination antiretrovirals were required
- G-CSF (type not specified) 5 mcg/kg SC once per day from days 4 to 13 or until ANC greater than 10k/μL.
- PCP prophylaxis with ONE of the following:
- Cotrimoxazole (dose/route/schedule not specified)
- Dapsone (Aczone) (dose/route/schedule not specified)
- Pentamidine (Nebupent) (dose/schedule not specified)
21-day cycle for 3 cycles for early disease, or minimum of 6 cycles or 2 past CR for advanced disease
Subsequent treatment
- AMC010, patients with stage I, IE, or nonbulky stage II disease: IFRT consolidation, beginning 3 weeks after the third cycle of chemotherapy
References
- AMC010: Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00003595
CODOX-M
CODOX-M: Cyclophosphamide, Oncovin, DOXorubicin, Methotrexate
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Wang et al. 2003 | 1988-2000 | Retrospective |
Note: Wang et al. 2003 retrospectively identified 8 HIV+ Burkitt lymphoma patients who had undergone treatment with CODOX-M/IVAC per the NCI 77-04 protocol.
- Patients are stratified into high and low risk:
- Low risk patients must fulfill all of the following criteria:
- Serum LDH within the institution's normal range (for the NCI, this was less than 350 IU/L)
- Single extraabdominal mass or completely resected abdominal disease
- Any patients which do not meet low risk criteria are classified as high risk
- Low risk patients must fulfill all of the following criteria:
This regimen is for low risk patients.
Chemotherapy
- Cyclophosphamide (Cytoxan) 800 mg/m2 IV once on day 1, then 200 mg/m2 IV once per day on days 2 to 5
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Methotrexate (MTX) 1200 mg/m2 IV over 60 minutes once on day 10, then 240 mg/m2/hour IV continuous infusion over 23 hours (total dose per cycle: 6720 mg/m2)
CNS therapy, prophylaxis
- Cytarabine (Ara-C) by the following age-based criteria:
- 3 years old or older: 70 mg IT once on day 1
- Younger than 3 years old: "appropriately reduced doses"
- Methotrexate (MTX) by the following age-based criteria:
- 3 years old or older: 12 mg IT once on day 3
- Younger than 3 years old: "appropriately reduced doses"
Supportive therapy
- Leucovorin (Folinic acid) 192 mg/m2 IV once on day 11, starting 36 hours after the start of the day 10 methotrexate, then 12 mg/m2 IV every 6 hours thereafter until serum methotrexate level is less than 50 nmol/L
3 cycles; each cycle starts on the same day that the patient's ANC is greater than 1000/μL
References
- Retrospective: Wang ES, Straus DJ, Teruya-Feldstein J, Qin J, Portlock C, Moskowitz C, Goy A, Hedrick E, Zelenetz AD, Noy A. Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer. 2003 Sep 15;98(6):1196-205. link to original article dosing details in manuscript have been reviewed by our editors PubMed
CODOX-M/IVAC
CODOX-M/IVAC: Cyclophosphamide, Oncovin, DOXorubicin, Methotrexate alternating with Ifosfamide, Vepesid (etoposide), Ara-C (cytarabine)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Magrath et al. 1996 (NCI 77-04) | 1977-1985 | Phase 2 |
Wang et al. 2003 | 1988-2000 | Retrospective |
Note: the original protocol of Magrath et al. 1996 did not comment on HIV status. Wang et al. 2003 retrospectively identified 8 HIV+ Burkitt lymphoma patients who had undergone treatment with CODOX-M/IVAC. CODOX-M and IVAC are given in an alternating fashion for a total of 4 cycles (A, B, A, B). Each cycle starts on the same day that the patient's ANC is greater than 1000/μL.
- Patients are stratified into high and low risk:
- Low risk patients must fulfill all of the following criteria:
- Serum LDH within the institution's normal range (for the NCI, this was less than 350 IU/L)
- Single extraabdominal mass or completely resected abdominal disease
- Any patients which do not meet low risk criteria are classified as high risk
- Low risk patients must fulfill all of the following criteria:
This regimen is for high-risk patients.
Chemotherapy, CODOX-M portion (cycles 1 & 3; "Part A")
- Cyclophosphamide (Cytoxan) 800 mg/m2 IV once on day 1, then 200 mg/m2 IV once per day on days 2 to 5
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Methotrexate (MTX) 1200 mg/m2 IV over 60 minutes once on day 10, then 240 mg/m2/hour IV continuous infusion over 23 hours (total dose per cycle: 6720 mg/m2)
CNS prophylaxis, CODOX-M portion (cycles 1 & 3; "Part A")
- Cytarabine (Ara-C) by the following age-based criteria:
- 3 years old or older: 70 mg IT once per day on days 1 & 3
- Younger than 3 years old: "appropriately reduced doses"
- Methotrexate (MTX) by the following age-based criteria:
- 3 years old or older: 12 mg IT once on day 15
- Younger than 3 years old: "appropriately reduced doses"
CNS treatment, CODOX-M portion
- Cytarabine (Ara-C) as follows:
- Cycle 1: 70 mg IT once on day 5 (in addition to doses above)
- Methotrexate (MTX) as follows:
- Cycle 1: 12 mg IT once on day 17 (in addition to dose above)
Supportive therapy, CODOX-M portion (cycles 1 & 3; "Part A")
- Leucovorin (Folinic acid) 192 mg/m2 IV once on day 11, starting 36 hours after the start of the day 10 methotrexate, then 12 mg/m2 IV every 6 hours thereafter until serum methotrexate level is less than 50 nmol/L
- GM-CSF 7.5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/μL
Chemotherapy, IVAC portion (cycles 2 & 4; "Part B")
- Ifosfamide (Ifex) 1500 mg/m2 IV once per day on days 1 to 5, with mesna
- Etoposide (Vepesid) 60 mg/m2 IV once per day on days 1 to 5
- Cytarabine (Ara-C) 2000 mg/m2 IV every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m2)
CNS prophylaxis, IVAC portion (cycles 2 & 4; "Part B")
- Methotrexate (MTX) 12 mg IT once on day 5
Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy during cycle 2:
- Cytarabine (Ara-C) 70 mg IT once per day on days 7 & 9
- Methotrexate (MTX) 12 mg IT once on day 17 (in addition to dose above)
Supportive therapy, IVAC portion (cycles 2 & 4; "Part B")
- Mesna (Mesnex) 360 mg/m2 IV every 3 hours on days 1 to 5, given with ifosfamide
- GM-CSF 7.5 mcg/kg SC once per day, starting on day 7 and continuing until ANC greater than 1000/μL
4 cycles (see note)
References
- NCI 77-04: 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Retrospective: Wang ES, Straus DJ, Teruya-Feldstein J, Qin J, Portlock C, Moskowitz C, Goy A, Hedrick E, Zelenetz AD, Noy A. Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer. 2003 Sep 15;98(6):1196-205. link to original article dosing details in manuscript have been reviewed by our editors PubMed
dmCODOX-M - Modified Magrath
dmCODOX-M: dose-modified Cyclophosphamide, Oncovin, DOXorubicin, Methotrexate
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Mead et al. 2008 (MRC/NCRI LY10) | 2002-2005 | Phase 2 |
- Patients are stratified into high and low risk:
- Low risk patients must fulfill at least 3 of the following criteria:
- Normal LDH
- WHO performance status of 0 or 1
- Ann Arbor stage I or II
- 0 or 1 extranodal sites of disease
- Any patients which do not meet low risk criteria are classified as high risk
- Low risk patients must fulfill at least 3 of the following criteria:
This regimen is for low risk patients.
Chemotherapy
- Cyclophosphamide (Cytoxan) 800 mg/m2 IV once on day 1, then 200 mg/m2 IV once per day on days 2 to 5
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Methotrexate (MTX) by the following age-based criteria:
- 65 years old or younger: 300 mg/m2 IV over 60 minutes once on day 10, then 2700 mg/m2 IV continuous infusion over 23 hours (total dose per cycle: 3000 mg/m2)
- Older than 65 years old: 100 mg/m2 IV over 60 minutes once on day 10, then 900 mg/m2 IV continuous infusion over 23 hours (total dose per cycle: 1000 mg/m2)
CNS therapy, prophylaxis
- Cytarabine (Ara-C) 70 mg IT once per day on days 1 & 3
- Methotrexate (MTX) 12 mg IT once on day 15
Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy:
- Cytarabine (Ara-C) 70 mg IT once on day 5 (in addition to doses above)
- Methotrexate (MTX) 12 mg IT once on day 17 (in addition to dose above)
Supportive therapy
- Leucovorin (Folinic acid) 15 mg PO once on day 18, 24 hours after intrathecal methotrexate
Supportive therapy
- Leucovorin (Folinic acid) 15 mg/m2 IV every 3 hours for 5 doses on day 11, starting 36 hours after start of the day 10 methotrexate, then 15 mg/m2 IV every 6 hours until methotrexate level is less than 50 nmol/L
- Leucovorin (Folinic acid) 15 mg PO once on day 16, 24 hours after intrathecal methotrexate
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/μL
- Allopurinol (Zyloprim) PO and/or Rasburicase (Elitek) prior to starting chemotherapy
3 cycles (see note) Note: Each cycle starts on the same day that the patient's ANC is greater than 1000/μL and unsupported (that is, without transfusion) platelet count greater than 75 x 109/L.
References
- MRC/NCRI LY10: 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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
dmCODOX-M/IVAC - Modified Magrath
dmCODOX-M/IVAC: dose-modified Cyclophosphamide, Oncovin, DOXorubicin, Methotrexate alternating with Ifosfamide, Vepesid (etoposide), Ara-C (cytarabine)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Mead et al. 2008 (MRC/NCRI LY10) | 2002-2005 | Phase 2 |
Note: This regimen is for high-risk patients. dmCODOX-M and IVAC are given in an alternating fashion for a total of 4 cycles (A, B, A, B). Each cycle starts on the same day that the patient's ANC is greater than 1000/μL and unsupported (that is, without transfusion) platelet count greater than 75 x 109/L.
- Patients are stratified into high and low risk:
- Low risk patients must fulfill at least 3 of the following criteria:
- Normal LDH
- WHO performance status of 0 or 1
- Ann Arbor stage I or II
- 0 or 1 extranodal sites of disease
- Any patients which do not meet low risk criteria are classified as high risk
- Low risk patients must fulfill at least 3 of the following criteria:
Chemotherapy, dmCODOX-M portion (cycles 1 & 3)
- Cyclophosphamide (Cytoxan) 800 mg/m2 IV once on day 1, then 200 mg/m2 IV once per day on days 2 to 5
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Methotrexate (MTX) by the following age-based criteria:
- 65 years old or younger: 300 mg/m2 IV over 60 minutes once on day 10, then 2700 mg/m2 IV continuous infusion over 23 hours (total dose per cycle: 3000 mg/m2)
- Older than 65 years old: 100 mg/m2 IV over 60 minutes once on day 10, then 900 mg/m2 IV continuous infusion over 23 hours (total dose per cycle: 1000 mg/m2)
CNS prophylaxis, dmCODOX-M portion (cycles 1 & 3)
- Cytarabine (Ara-C) 70 mg IT once per day on days 1 & 3
- Methotrexate (MTX) 12 mg IT once on day 15
CNS treatment, dmCODOX-M portion (cycles 1 & 3)
Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy:
- Cytarabine (Ara-C) 70 mg IT once on day 5 (in addition to doses above)
- Methotrexate (MTX) 12 mg IT once on day 17 (in addition to dose above)
Supportive therapy, dmCODOX-M portion (cycles 1 & 3)
- Leucovorin (Folinic acid) 15 mg/m2 IV every 3 hours for 5 doses on day 11, starting 36 hours after start of the day 10 methotrexate, then 15 mg/m2 IV every 6 hours until methotrexate level is less than 50 nmol/L
- Leucovorin (Folinic acid) 15 mg PO once on day 16, 24 hours after intrathecal methotrexate
- If CNS+: Leucovorin (Folinic acid) 15 mg PO once on day 18, 24 hours after intrathecal methotrexate
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/μL
- Allopurinol (Zyloprim) PO and/or Rasburicase (Elitek) prior to starting chemotherapy
Chemotherapy, IVAC portion (cycles 2 & 4)
- Ifosfamide (Ifex) by the following age-based criteria:
- 65 years old or younger: 1500 mg/m2 IV over 60 minutes once per day on days 1 to 5
- Older than 65 years old: 1000 mg/m2 IV over 60 minutes once per day on days 1 to 5
- Etoposide (Vepesid) 60 mg/m2 IV over 60 minutes once per day on days 1 to 5
- Cytarabine (Ara-C) by the following age-based criteria:
- 65 years old or younger: 2000 mg/m2 IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m2)
- Older than 65 years old: 1000 mg/m2 IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 4000 mg/m2)
Supportive therapy, IVAC portion (cycles 2 & 4)
- Mesna (Mesnex) by the following age-based criteria:
- 65 years old or younger: 300 mg/m2 (mixed with ifosfamide) IV over 60 minutes once per day on days 1 to 5, then 300 mg/m2 IV every four hours for 2 doses on days 1 to 5
- Older than 65 years old: 200 mg/m2 (mixed with ifosfamide) IV over 60 minutes once per day on days 1 to 5, then 200 mg/m2 IV every four hours for 2 doses on days 1 to 5
- Leucovorin (Folinic acid) 15 mg PO once on day 6, 24 hours after intrathecal methotrexate
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 7 and continuing until ANC greater than 1000/μL
CNS prophylaxis, IVAC portion (cycles 2 & 4)
- Methotrexate (MTX) 12 mg IT once on day 5
4 cycles (see note)
References
- MRC/NCRI LY10: 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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
EPOCH, dose-escalated
EPOCH: Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Little et al. 2003 | 1995-04 to 2000-08 | Non-randomized |
Note: the paper refers to this regimen as dose-adjusted EPOCH but to avoid confusion with the other version of dose-adjusted EPOCH, we refer to it as dose-escalated EPOCH, here.
Chemotherapy
- Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m2)
- Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m2)
- Cyclophosphamide (Cytoxan) by the following laboratory-based criteria:
- CD4+ count less than 100/μL: 187 mg/m2 IV over 15 minutes once on day 5
- CD4+ count more than 100/μL: 375 mg/m2 IV over 15 minutes once on day 5
- Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
Supportive therapy
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC greater than 5000/μL past nadir
21-day cycle for 6 cycles
Dose and schedule modifications
- In each subsequent cycle, increase cyclophosphamide dose by 187 mg/m2 (maximum dose 750 mg/m2) if the neutrophil nadir is greater than 500/μL and platelet nadir is greater than 25 x 109/L. Decrease dose by 187 mg/m2 if the neutrophil nadir is less than 500/μL or platelet nadir is less than 25 x 109/L.
References
- Little RF, Pittaluga S, Grant N, Steinberg SM, Kavlick MF, Mitsuya H, Franchini G, Gutierrez M, Raffeld M, Jaffe ES, Shearer G, Yarchoan R, Wilson WH. Highly effective treatment of acquired immunodeficiency syndrome-related lymphoma with dose-adjusted EPOCH: impact of antiretroviral therapy suspension and tumor biology. Blood. 2003 Jun 15;101(12):4653-9. Epub 2003 Feb 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed
GMALL-R
GMALL-R: German Multicenter Study Group for the Treatment of Adult Acute Lymphoblastic Leukemia, Rituximab
Study | Dates of enrollment | Evidence |
---|---|---|
Ribera et al. 2013 (Burkimab) | Not reported | Phase 2 |
Note: Numbering of days is based on pre-phase->A->B->C; however, certain patient populations received different ordering of regimen, see below.
Pre-phase
Chemotherapy
- Cyclophosphamide (Cytoxan) 200 mg/m2 IV over 60 minutes once per day on days 1 to 5
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 IV bolus once per day on days 1 to 5
5-day course, followed by:
Induction
Targeted therapy, A cycle
- Rituximab (Rituxan) 375 mg/m2 IV over 4 hours once on day 7
Chemotherapy, A cycle
- Vincristine (Oncovin) 2 mg IV bolus once on day 8
- Methotrexate (MTX) by the following age-based criteria:
- 55 years old or younger: 1500 mg/m2 IV continuous infusion over 24 hours, started on day 8
- Older than 55 years old: 750 mg/m2 IV continuous infusion over 24 hours, started on day 8
- Ifosfamide (Ifex) 800 mg/m2 IV over 60 minutes once per day on days 8 to 12
- Teniposide (Vumon) 100 mg/m2 IV over 60 minutes once per day on days 11 & 12
- Cytarabine (Ara-C) by the following age-based criteria:
- 55 years old or younger: 150 mg/m2 IV over 60 minutes twice per day on days 11 & 12
- Older than 55 years old: 75 mg/m2 IV over 60 minutes twice per day on days 11 & 12
Glucocorticoid therapy, A cycle
- Dexamethasone (Decadron) 10 mg/m2 IV bolus once per day on days 8 to 12
Supportive therapy, A cycle
- Leucovorin (Folinic acid) (dose/route/schedule not specified), starting 12 hours after methotrexate infusion
Targeted therapy, B cycle
- Rituximab (Rituxan) 375 mg/m2 IV over 4 hours once on day 28
Chemotherapy, B cycle
- Vincristine (Oncovin) 2 mg IV bolus once on day 29
- Methotrexate (MTX) by the following age-based criteria:
- 55 years old or younger: 1500 mg/m2 IV continuous infusion over 24 hours, started on day 29
- Older than 55 years old: 750 mg/m2 IV continuous infusion over 24 hours, started on day 29
- Cyclophosphamide (Cytoxan) 200 mg/m2 IV over 60 minutes once per day on days 29 to 33
- Doxorubicin (Adriamycin) 25 mg/m2 IV over 15 minutes once per day on days 32 & 33
Glucocorticoid therapy, B cycle
- Dexamethasone (Decadron) 10 mg/m2 IV bolus once per day on days 29 to 33
Supportive therapy, B cycle
- Leucovorin (Folinic acid) (dose/route/schedule not specified), starting 12 hours after methotrexate infusion
Targeted therapy, C cycle
- Rituximab (Rituxan) 375 mg/m2 IV over 4 hours once on day 49
Chemotherapy, C cycle
- Vindesine (Eldisine) 3 mg/m2 (maximum dose of 5 mg) IV bolus once on day 50
- Methotrexate (MTX) by the following age-based criteria, starting on day 50:
- 55 years old or younger: 1500 mg/m2 IV continuous infusion over 24 hours
- Older than 55 years old: 750 mg/m2 IV continuous infusion over 24 hours
- Etoposide (Vepesid) 250 mg/m2 IV over 60 minutes once per day on days 53 & 54
- Cytarabine (Ara-C) by the following age-based criteria, on day 54:
- 55 years old or younger: 2000 mg/m2 IV over 3 hours twice per day
- Older than 55 years old: 1000 mg/m2 IV over 3 hours twice per day
Glucocorticoid therapy, C cycle
- Dexamethasone (Decadron) 10 mg/m2 IV bolus once per day on days 50 to 54
Supportive therapy, C cycle
- Leucovorin (Folinic acid) (dose/route/schedule not specified), starting 12 hours after methotrexate infusion
Give regimen by the following age- and stage-based criteria:
- Advanced stage and younger than 55 years: A->B->C for 2 courses (6 total cycles)
- Older than 55 years old: Alternate A & B for 3 courses (6 total cycles)
- Localized stage: 4 total cycles (unclear from protocol if this means A alternating with B or A->B->C->A)
Prophylaxis
CNS therapy
- Methotrexate (MTX) 15 mg IT once per day on days 1, 8, 12, 29, 33
- Cytarabine (Ara-C) 40 mg IT once per day on days 1, 8, 12, 29, 33
- Dexamethasone (Decadron) 20 mg IT once per day on days 1, 8, 12, 29, 33
8 doses total
References
- Burkimab: Ribera JM, García O, Grande C, Esteve J, Oriol A, Bergua J, González-Campos J, Vall-Llovera F, Tormo M, Hernández-Rivas JM, García D, Brunet S, Alonso N, Barba P, Miralles P, Llorente A, Montesinos P, Moreno MJ, Hernández-Rivas JÁ, Bernal T. Dose-intensive chemotherapy including rituximab in Burkitt's leukemia or lymphoma regardless of human immunodeficiency virus infection status: final results of a phase 2 study (Burkimab). Cancer. 2013 May 1;119(9):1660-8. Epub 2013 Jan 29. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00388193
m-BACOD
m-BACOD: methotrexate (moderate dose), Bleomycin, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Dexamethasone
Regimen variant #1, "low-dose" #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kaplan et al. 1997 (ACTG 142) | 1991-1994 | Phase 3 (E-de-esc) | m-BACOD; standard-dose | Did not meet primary endpoint of OS |
Note: this is of historical interest, only.
Chemotherapy
- Methotrexate (MTX) 200 mg/m2 IV once on day 15
- Bleomycin (Blenoxane) 4 units/m2 IV once on day 1
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 300 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
Glucocorticoid therapy
- Dexamethasone (Decadron) 3 mg/m2 PO once per day on days 1 to 5
Supportive therapy
- Sargramostim (Leukine) 5 mcg/kg SC once per day on days 4 to 13 (as needed)
CNS therapy, prophylaxis
- Cytarabine (Ara-C) as follows:
- Cycle 1: 50 mg IT once per day on days 1, 8, 15
- Cycle 2: 50 mg IT once on day 1
21-day cycle for 2 cycles past complete remission (minimum of 4 cycles)
Regimen variant #2, "low-dose" #2
Study | Dates of enrollment | Evidence |
---|---|---|
Levine et al. 1991 | 1987-06 to 1988-11 | Non-randomized |
Note: this is of historical interest, only; the MTX dose is slightly higher than above.
Chemotherapy
- Methotrexate (MTX) 500 mg/m2 IV once on day 15
- Bleomycin (Blenoxane) 4 units/m2 IV once on day 1
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 300 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
Glucocorticoid therapy
- Dexamethasone (Decadron) 3 mg/m2 PO once per day on days 1 to 5
Supportive therapy
CNS therapy, prophylaxis
- Cytarabine (Ara-C) 50 mg IT once per day on days 1, 8, 21, 28
4 to 6 cycles
Regimen variant #3, "standard-dose"
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kaplan et al. 1997 (ACTG 142) | 1991-1994 | Phase 3 (C) | m-BACOD; low-dose | Did not meet primary endpoint of OS |
Note: this is of historical interest, only.
Chemotherapy
- Methotrexate (MTX) 200 mg/m2 IV once on day 15
- Bleomycin (Blenoxane) 4 units/m2 IV once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
Glucocorticoid therapy
- Dexamethasone (Decadron) 6 mg/m2 PO once per day on days 1 to 5
Supportive therapy
- Sargramostim (Leukine) 5 mcg/kg SC once per day on days 4 to 13
CNS therapy, prophylaxis
- Cytarabine (Ara-C) as follows:
- Cycle 1: 50 mg IT once per day on days 1, 8, 15
- Cycle 2: 50 mg IT once on day 1
21-day cycle for 2 cycles past complete remission (minimum of 4 cycles)
References
- Levine AM, Wernz JC, Kaplan L, Rodman N, Cohen P, Metroka C, Bennett JM, Rarick MU, Walsh C, Kahn J, Miles S, Ehmann WC, Feinberg J, Nathwani B, Gill PS, Mitsuyasu R. Low-dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance in AIDS-related lymphoma: a prospective multi-institutional trial. JAMA. 1991 Jul 3;266(1):84-8. link to original article dosing details in abstract have been reviewed by our editors PubMed
- ACTG 142: Kaplan LD, Straus DJ, Testa MA, Von Roenn J, Dezube BJ, Cooley TP, Herndier B, Northfelt DW, Huang J, Tulpule A, Levine AM; National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. N Engl J Med. 1997 Jun 5;336(23):1641-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
R-CDOP
R-CDOP: Rituximab, Cyclophosphamide, Doxil (Pegylated liposomal doxorubicin), Oncovin (Vincristine), Prednisone
DR-COP: Doxil (pegylated liposomal doxorubicin), Rituximab, Cyclophosphamide, Oncovin, Prednisone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Levine et al. 2012 (AMC047) | 2007 to not reported | Phase 2 |
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Pegylated liposomal doxorubicin (Doxil) 40 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
CNS therapy, prophylaxis
- "CNS prophylaxis was mandated in patients with involvement of bone marrow, testis, sinuses, or epidural regions and with stage IV and/or at least two extranodal sites, with specific regimen left to physician discretion."
Supportive therapy
- Highly Active Antiretroviral Therapy (HAART) required; specific regimen left to physician discretion. Use of zidovudine was not allowed.
- G-CSF prophylaxis, starting on day 3 and continuing until beyond nadir of blood counts, with one of the following:
- Erythropoietin (e.g. Epoetin alfa (Procrit) or Darbepoetin alfa (Aranesp)) at physician discretion
- PCP prophylaxis required
- Oral fluoroquinolone if CD4 cell count less than or equal to 100 and ANC less than 500/μL at entry or during treatment
21- to 28-day cycle for up to 6 cycles
References
- AMC047: Levine AM, Noy A, Lee JY, Tam W, Ramos JC, Henry DH, Parekh S, Reid EG, Mitsuyasu R, Cooley T, Dezube BJ, Ratner L, Cesarman E, Tulpule A. Pegylated liposomal doxorubicin, rituximab, cyclophosphamide, vincristine, and prednisone in AIDS-related lymphoma: AIDS Malignancy Consortium study 047. J Clin Oncol. 2013 Jan 1;31(1):58-64. Epub 2012 Nov 19. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00389818
R-CHOP
R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone
Regimen variant #1, 3 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kaplan et al. 2005 (AMC010) | 1998-2002 | Phase 3 (E-esc) | CHOP | Did not meet primary endpoint of CR rate |
Note: This regimen variant was intended for patients with stage I, IE, or nonbulky stage II disease.
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day -2
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive therapy
- Combination antiretrovirals were required
- G-CSF (type not specified) 5 mcg/kg SC once per day from days 4 to 13 or until ANC greater than 10k/μL.
- PCP prophylaxis with ONE of the following:
- Cotrimoxazole (dose/schedule not specified)
- Dapsone (Aczone) (dose/schedule not specified)
- Pentamidine (Nebupent) (dose/schedule not specified)
21-day cycle for 3 cycles for early disease, or minimum of 6 cycles or 2 past CR for advanced disease
Subsequent treatment
- IFRT consolidation x 4000 cGy
Regimen variant #2, prednisone 40 mg/m2
Study | Dates of enrollment | Evidence |
---|---|---|
Boué et al. 2006 | Not reported | Phase 2 |
Ribera et al. 2007x | 2001-04 to 2006-04 | Phase 2 |
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- In Boué et al. 2006, first dose was given on day -1
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
CNS therapy, prophylaxis
- Ribera et al. 2007x: To be given with each cycle; day of administration not reported.
- Methotrexate (MTX) 12 mg IT
- Cytarabine (Ara-C) 40 mg IT
- Hydrocortisone (Cortef) 20 mg IT
Supportive therapy
- Combination antiretrovirals were required: one or two protease inhibitors and two nucleoside reverse transcriptase inhibitors
- PCP prophylaxis with ONE of the following:
- Cotrimoxazole 160/800 mg PO TIW
- Pentamidine (Nebupent) 300 mg inhaled (schedule not specified)
21-day cycle for 6 cycles
Subsequent treatment
- Ribera et al. 2007x, patients with bulky disease or a residual mass: IFRT consolidation (details not provided)
Regimen variant #3, prednisone 100 mg
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kaplan et al. 2005 (AMC010) | 1998-2002 | Phase 3 (E-esc) | CHOP | Did not meet primary endpoint of CR rate |
Note: This regimen variant was intended for patients with advanced disease.
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day -2
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive therapy
- Combination antiretrovirals were required
- G-CSF (type not specified) 5 mcg/kg SC once per day from days 4 to 13 or until ANC greater than 10k/μL.
- PCP prophylaxis with ONE of the following:
- Cotrimoxazole (dose/schedule not specified)
- Dapsone (Aczone) (dose/schedule not specified)
- Pentamidine (Nebupent) (dose/schedule not specified)
21-day cycle for a minimum of 6 cycles or 2 past CR
Subsequent treatment
- AMC010, PR/CR: Rituximab maintenance
References
- AMC010: Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00003595
- Boué F, Gabarre J, Gisselbrecht C, Reynes J, Cheret A, Bonnet F, Billaud E, Raphael M, Lancar R, Costagliola D. Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin's lymphoma. J Clin Oncol. 2006 Sep 1;24(25):4123-8. Epub 2006 Aug 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Ribera JM, Oriol A, Morgades M, González-Barca E, Miralles P, López-Guillermo A, Gardella S, López A, Abella E, García M; PETHEMA; GELTAMO; GELCAB; GESIDA. Safety and efficacy of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab in patients with human immunodeficiency virus-associated diffuse large B-cell lymphoma: results of a phase II trial. Br J Haematol. 2008 Feb;140(4):411-9. Epub 2007 Dec 19. link to original article dosing details in manuscript have been reviewed by our editors PubMed
R-CODOX-M
R-CODOX-M: Rituximab, Cyclophosphamide, Oncovin (Vincristine), DOXorubicin, Methotrexate
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Noy et al. 2015 (AMC 048) | 2007-2010 | Phase 2 |
Note: This regimen was intended for low-risk HIV-associated Burkitt lymphoma, and was the first published prospective regimen to explicitly use rituximab. This is sometimes called modified Magrath but is in fact a second modification to the modified Magrath described by LaCasce et al. 2004.
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Cyclophosphamide (Cytoxan) 800 mg/m2 IV once per day on days 1 & 2
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Methotrexate (MTX) 3000 mg/m2 IV once on day 15
CNS therapy, prophylaxis
- Cytarabine (Ara-C) 50 mg IT once on day 1
- Methotrexate (MTX) 12 mg IT once on day 1
- Hydrocortisone (Cortef) 50 mg IT once on day 1
Supportive therapy
- Leucovorin (Folinic acid) 200 mg/m2 IV once 24 hours after methotrexate, then 25 mg/m2 IV every 6 hours until methotrexate level is less than 50 nmol/L
- Pegfilgrastim (Neulasta) 6 mg SC once on day 3
- Filgrastim (Neupogen) (dose not specified) SC once per day, starting once methotrexate level is less than 50 nmol/L (approximately day 18) and continuing until ANC greater than 1000/μL
21- to 28-day cycle for 3 cycles
References
- Lacasce A, Howard O, Lib S, Fisher D, Weng A, Neuberg D, Shipp M. Modified Magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma. 2004 Apr;45(4):761-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Retrospective: Barnes JA, Lacasce AS, Feng Y, Toomey CE, Neuberg D, Michaelson JS, Hochberg EP, Abramson JS. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: a retrospective analysis. Ann Oncol. 2011 Aug;22(8):1859-64. Epub 2011 Feb 21. link to original article contains partial protocol PubMed content property of HemOnc.org
- Retrospective: Kassam S, Bower M, Lee SM, de Vos J, Fields P, Gandhi S, Nelson M, Montoto S, Tenant-Flowers M, Burns F, Marcus R, Edwards SG, Cwynarski K. A retrospective, multi-center analysis of treatment intensification for HIV-positive patients with high-risk diffuse large B-cell lymphoma. Leuk Lymphoma. 2013 Sep;54(9):1921-7. Epub 2013 Jan 4. link to original article PubMed
- AMC 048: Noy A, Lee JY, Cesarman E, Ambinder R, Baiocchi R, Reid E, Ratner L, Wagner-Johnston N, Kaplan L. AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Blood. 2015 Jul 9;126(2):160-6. Epub 2015 May 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00392834
R-CODOX-M/R-IVAC
R-CODOX-M/R-IVAC: Rituximab, Cyclophosphamide, Oncovin (Vincristine), DOXorubicin, Methotrexate alternating with Rituximab, Ifosfamide, Vepesid (Etoposide), Ara-C (Cytarabine)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
LaCasce et al. 2004 | Not reported | Phase 2, fewer than 20 pts |
Noy et al. 2015 (AMC 048) | 2007-2010 | Phase 2 |
Note: This protocol was intended for high-risk HIV-associated Burkitt lymphoma, and was the first published prospective regimen to explicitly use rituximab. This is sometimes called modified Magrath but is in fact a second modification to the modified Magrath described in LaCasce et al. 2004. Note that the preferred sequence is A, B, A, B but the authors note that for patients with anasarca or other concerns for retaining MTX, the sequence can be B, A, B, A. Also note that the paper does not specify whether hydrocortisone is used with the day 3 IT chemo; the authors have clarified (December 31, 2017) that this is left to institutional policy.
Targeted therapy, both portions (cycles 1 to 4)
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy, R-CODOX-M portion (cycles 1 & 3; "Part A")
- Cyclophosphamide (Cytoxan) 800 mg/m2 IV once per day on days 1 & 2
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Methotrexate (MTX) 3000 mg/m2 IV once on day 15
Supportive therapy, R-CODOX-M portion (cycles 1 & 3; "Part A")
- Leucovorin (Folinic acid) 200 mg/m2 IV once 24 hours after methotrexate, then 25 mg/m2 IV every 6 hours until methotrexate level is less than 50 nmol/L
- Filgrastim (Neupogen) (dose not specified) SC once per day, starting once methotrexate level is less than 50 nmol/L (approximately day 18) and continuing until ANC greater than 1000/μL
CNS prophylaxis, R-CODOX-M portion (cycles 1 & 3; "Part A")
- Cytarabine (Ara-C) 50 mg IT once per day on days 1 & 3
- Methotrexate (MTX) 12 mg IT once on day 1
- Hydrocortisone (Cortef) 50 mg IT once on day 1
Chemotherapy, R-IVAC portion (cycles 2 & 4; "Part B")
- Ifosfamide (Ifex) 1500 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 7500 mg/m2)
- Etoposide (Vepesid) 60 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 300 mg/m2)
- Cytarabine (Ara-C) 2000 mg/m2 IV every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m2)
Supportive therapy, R-IVAC portion (cycles 2 & 4; "Part B")
- Mesna (Mesnex) 1500 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 7500 mg/m2)
- Pegfilgrastim (Neulasta) 6 mg SC once on day 6
CNS prophylaxis, R-IVAC portion (cycles 2 & 4; "Part B")
- Methotrexate (MTX) 12 mg IT once on day 5
4 cycles (see note)
References
- Lacasce A, Howard O, Lib S, Fisher D, Weng A, Neuberg D, Shipp M. Modified Magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma. 2004 Apr;45(4):761-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Retrospective: Barnes JA, Lacasce AS, Feng Y, Toomey CE, Neuberg D, Michaelson JS, Hochberg EP, Abramson JS. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: a retrospective analysis. Ann Oncol. 2011 Aug;22(8):1859-64. Epub 2011 Feb 21. link to original article contains partial protocol PubMed content property of HemOnc.org
- Retrospective: Kassam S, Bower M, Lee SM, de Vos J, Fields P, Gandhi S, Nelson M, Montoto S, Tenant-Flowers M, Burns F, Marcus R, Edwards SG, Cwynarski K. A retrospective, multi-center analysis of treatment intensification for HIV-positive patients with high-risk diffuse large B-cell lymphoma. Leuk Lymphoma. 2013 Sep;54(9):1921-7. Epub 2013 Jan 4. link to original article PubMed
- AMC 048: Noy A, Lee JY, Cesarman E, Ambinder R, Baiocchi R, Reid E, Ratner L, Wagner-Johnston N, Kaplan L. AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Blood. 2015 Jul 9;126(2):160-6. Epub 2015 May 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00392834
R-EPOCH, dose-escalated
R-EPOCH: Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sparano et al. 2010 (AMC034) | 2002-2006 | Randomized Phase 2 (E-switch-ic) | EPOCH, then R | Not reported1 |
1While this was a randomized trial, the primary efficacy endpoint was a historical control; see article for details.
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once (day not specified), given first
Chemotherapy
- Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m2)
- Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m2)
- Cyclophosphamide (Cytoxan) by the following laboratory-based criteria:
- CD4+ count less than 100/μL: 187 mg/m2 IV over 15 minutes once on day 5
- CD4+ count more than 100/μL: 375 mg/m2 IV over 15 minutes once on day 5
- Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
Supportive therapy
- EITHER Filgrastim (Neupogen) 5 mcg/kg SC 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 once 24 hours after EPOCH is completed
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO TIW (e.g. Monday, Wednesday, Friday)
- Fluconazole (Diflucan) 100 mg PO once per day
- Ciprofloxacin (Cipro) 500 mg PO twice per day, 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
21-day cycle for 6 to 8 cycles
Dose and schedule modifications
- In each subsequent cycle, increase cyclophosphamide dose by 187 mg/m2 if the neutrophil nadir is greater than 500/μL and platelet nadir is greater than 25 x 109/L. Decrease dose by 187 mg/m2 if the neutrophil nadir is less than 500/μL or platelet nadir is less than 25 x 109/L.
References
- AMC034: Sparano JA, Lee JY, Kaplan LD, Levine AM, Ramos JC, Ambinder RF, Wachsman W, Aboulafia D, Noy A, Henry DH, Von Roenn J, Dezube BJ, Remick SC, Shah MH, Leichman L, Ratner L, Cesarman E, Chadburn A, Mitsuyasu R; AIDS Malignancy Consortium. Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma. Blood. 2010 Apr 15;115(15):3008-16. Epub 2009 Dec 18. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00049036
SC-EPOCH-RR
SC-EPOCH-RR: Short Course Rituximab, Etoposide, Prednisone, Oncovin, Cyclophosphamide, Hydroxydaunorubicin, with dose-dense Rituximab
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Dunleavy et al. 2013 (NCI 93-C-0133HIV) | 2000-11 to 2009-12 | Phase 2, fewer than 20 pts in this arm |
Dunleavy et al. 2010 (NCI 97-C-0040) | 2001-06 to 2009-04 | Phase 2 |
Note: NCI 97-C-0040 reported on HIV+ DLBCL patients, whereas NCI 93-C-0133 reported on HIV+ Burkitt lymphoma patients. The regimen is the same.
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV over 3 hours once per day on days 1 & 5
Chemotherapy
- Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m2)
- Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m2)
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 2 hours once on day 5
- Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
CNS therapy, prophylaxis
- Methotrexate (MTX) as follows:
- Cycles 3 to 5: 12 mg IT once per day on days 1 & 5
Supportive therapy
- Filgrastim (Neupogen) 300 mcg SC once per day, starting on day 6, continue until ANC greater than 5k/μL above nadir
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO TIW (e.g. Monday, Wednesday, Friday)
- Omeprazole (Prilosec) 20 mg PO once per day (or equivalent)
- Docusate (Colace) and Sennosides (Senna) 2 tablets PO twice per day as necessary for constipation
- Lactulose 20 gms PO every 6 hours as necessary for constipation.
21-day cycle for 3 to 6 cycles, one cycle beyond CR
Dose and schedule modifications
- Cyclophosphamide (Cytoxan):
- In the subsequent cycle, decrease dose by 187 mg/m2 if ANC was less than 500/μL for 2 to 4 days or platelets were less than 25 x 109/L for 2 to 4 days.
- In the subsequent cycle, decrease dose by 375 mg/m2 if ANC was less than 500/μL for 5 or more days or platelets were less than 25 x 109/L for 5 or more days.
- If dose-reduced in prior cycle, increase dose by 187 mg/m2, up to maximum of 750 mg/m2, if ANC was greater than 500/μL and platelets were greater than 25 x 109/L for the entire cycle.
References
- NCI 97-C-0040: Dunleavy K, Little RF, Pittaluga S, Grant N, Wayne AS, Carrasquillo JA, Steinberg SM, Yarchoan R, Jaffe ES, Wilson WH. The role of tumor histogenesis, FDG-PET, and short-course EPOCH with dose-dense rituximab (SC-EPOCH-RR) in HIV-associated diffuse large B-cell lymphoma. Blood. 2010 Apr 15;115(15):3017-24. Epub 2010 Feb 3. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00001563
- NCI 93-C-0133HIV: Dunleavy K, Pittaluga S, Shovlin M, Steinberg SM, Cole D, Grant C, Widemann B, Staudt LM, Jaffe ES, Little RF, Wilson WH. Low-intensity therapy in adults with Burkitt's lymphoma. N Engl J Med. 2013 Nov 14;369(20):1915-25. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00001337
Stanford V
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Spina et al. 2002 | 1997-05 to 2001-10 | Phase 2 |
Note: this regimen was for HIV-associated Hodgkin lymphoma, unfavorable stage I or advanced stage.
Chemotherapy
- Doxorubicin (Adriamycin) 25 mg/m2 IV once per week on weeks 1, 3, 5, 7, 9, 11
- Vinblastine (Velban) 6 mg/m2 IV once per week on weeks 1, 3, 5, 7, 9, 11
- Mechlorethamine (Mustargen) 6 mg/m2 IV once per week on weeks 1, 5, 9
- Etoposide (Vepesid) 60 mg/m2 IV once per day for two successive days on weeks 3, 7, 11
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once per week on weeks 2, 4, 6, 8, 10, 12
- Bleomycin (Blenoxane) 5 units/m2 IV once per week on weeks 2, 4, 6, 8, 10, 12
Glucocorticoid therapy
- Prednisone (Sterapred) as follows:
- Weeks 1 to 10: 40 mg/m2 PO every other day
- Weeks 11 & 12: taper by 10 mg/m2 every other day until off
Supportive therapy
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 3 to 7, 9 to 13, 17 to 21, 23 to 26
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO once per day throughout the course of treatment
- Fluconazole (Diflucan) 100 mg PO once per day throughout the course of treatment
12-week course
References
- Spina M, Gabarre J, Rossi G, Fasan M, Schiantarelli C, Nigra E, Mena M, Antinori A, Ammassari A, Talamini R, Vaccher E, di Gennaro G, Tirelli U. Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection. Blood. 2002 Sep 15;100(6):1984-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Consolidation after upfront therapy
Radiation therapy
IFRT: Involved Field Radiation Therapy
Regimen variant #1, 3600 cGy of IFRT
Study | Dates of enrollment | Evidence |
---|---|---|
Spina et al. 2002 | 1997-05 to 2001-10 | Phase 2 |
Preceding treatment
- Stanford V induction x 12 wk
Radiotherapy
- External beam radiotherapy 3600 cGy in 200 cGy fractions, 5 days per week
4-week course
Regimen variant #2, 4000 cGy of IFRT
Study | Dates of enrollment | Evidence |
---|---|---|
Kaplan et al. 2005 (AMC010) | 1998-2002 | Non-randomized part of phase 3 RCT |
Note: This regimen variant was intended for patients with stage I, IE, or nonbulky stage II disease.
Preceding treatment
- Induction R-CHOP x 3
Subsequent treatment
- AMC010, PR/CR: Rituximab maintenance
References
- Spina M, Gabarre J, Rossi G, Fasan M, Schiantarelli C, Nigra E, Mena M, Antinori A, Ammassari A, Talamini R, Vaccher E, di Gennaro G, Tirelli U. Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection. Blood. 2002 Sep 15;100(6):1984-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- AMC010: Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00003595
Rituximab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Kaplan et al. 2005 (AMC010) | 1998-2002 | Non-randomized part of phase 3 RCT |
Preceding treatment
References
- AMC010: Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00003595
Consolidation after salvage therapy
BEAM, then auto HSCT
BEAM: BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Re et al. 2003 | 2000-09 to 2003-04 | Phase 2 | |
Alvarnas et al. 2016 (BMT CTN 0803/AMC 071) | 2010-04 to 2013-03 | Phase 2 | 1-year OS: 87% (95% CI, 72-94.5) |
Note: days of chemotherapy are slightly different in Re et al. 2003; see paper for details.
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 100 mg/m2 IV every 12 hours on days -5 to -2 (total dose: 800 mg/m2)
- Cytarabine (Ara-C) 100 mg/m2 IV every 12 hours on days -5 to -2 (total dose: 800 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Hematopoietic stem cells are reinfused on day 0
References
- Re A, Cattaneo C, Michieli M, Casari S, Spina M, Rupolo M, Allione B, Nosari A, Schiantarelli C, Vigano M, Izzi I, Ferremi P, Lanfranchi A, Mazzuccato M, Carosi G, Tirelli U, Rossi G. High-dose therapy and autologous peripheral-blood stem-cell transplantation as salvage treatment for HIV-associated lymphoma in patients receiving highly active antiretroviral therapy. J Clin Oncol. 2003 Dec 1;21(23):4423-7. Epub 2003 Oct 27. link to original article PubMed
- BMT CTN 0803/AMC 071: Alvarnas JC, Le Rademacher J, Wang Y, Little RF, Akpek G, Ayala E, Devine S, Baiocchi R, Lozanski G, Kaplan L, Noy A, Popat U, Hsu J, Morris LE Jr, Thompson J, Horowitz MM, Mendizabal A, Levine A, Krishnan A, Forman SJ, Navarro WH, Ambinder R. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial. Blood. 2016 Aug 25;128(8):1050-8. Epub 2016 Jun 13. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01141712