Difference between revisions of "Hodgkin lymphoma, nodular lymphocyte-predominant"
Warner-admin (talk | contribs) m (Text replacement - "{| border="1" style="text-align:center;" !align="left"" to "{| class="wikitable" style="width: 100%; text-align:center;"") |
Warner-admin (talk | contribs) m (Text replacement - "'''contains dosing details in abstract'''" to "'''dosing details in abstract have been reviewed by our editors'''") |
||
(113 intermediate revisions by 4 users not shown) | |||
Line 1: | Line 1: | ||
− | + | <span id="BackToTop"></span> | |
− | + | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | |
− | + | [[#top|Back to Top]] | |
− | + | </div> | |
+ | {{#lst:Editorial board transclusions|inhl}} | ||
+ | ''This page contains histology-specific studies. For the more general classical Hodgkin lymphoma page, follow [[Classical Hodgkin lymphoma|this link]]. | ||
+ | *''We have moved [[How I Treat]] articles to a dedicated page.'' | ||
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
|- | |- | ||
− | |<div style="background-color: # | + | |<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div> |
− | <div style="background-color: # | + | <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div> |
|} | |} | ||
{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
− | |||
=Guidelines= | =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.''' | ||
+ | ==JCO "Oncology Grand Rounds"== | ||
+ | *'''2020:''' Bartlett [https://doi.org/10.1200/jco.19.02816 Treatment of Nodular Lymphocyte Hodgkin Lymphoma: The Goldilocks Principle] [https://pubmed.ncbi.nlm.nih.gov/31922929 PubMed] | ||
− | == | + | ==NCCN== |
− | *[https://www.nccn.org/ | + | *''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1439 NCCN Guidelines - Hodgkin Lymphoma].'' |
=Untreated= | =Untreated= | ||
− | |||
==ABVD {{#subobject:4c2988|Regimen=1}}== | ==ABVD {{#subobject:4c2988|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
ABVD: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine | ABVD: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:c0fc65|Variant=1}}=== | ===Regimen {{#subobject:c0fc65|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | | | + | !style="width: 33%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2011-07-365932 Savage et al. 2011] |
− | |style="background-color:# | + | |1966-02 to 2009-05 |
+ | |style="background-color:#ffffbe"|Retrospective | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2013-12-541078 Xing et al. 2014] |
− | |style="background-color:# | + | |1970-2011 |
+ | |style="background-color:#ffffbe"|Retrospective | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: there are some reports of using rituximab although schedule & number of cycles is not well-established. | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 15 | *[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 15 | ||
Line 40: | Line 46: | ||
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV once per day on days 1 & 15 | *[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV once per day on days 1 & 15 | ||
*[[Dacarbazine (DTIC)]] 375 mg/m<sup>2</sup> IV once per day on days 1 & 15 | *[[Dacarbazine (DTIC)]] 375 mg/m<sup>2</sup> IV once per day on days 1 & 15 | ||
− | |||
− | |||
'''28-day cycle for 2 to 6 cycles''' based on stage, response, and whether radiation therapy is used. | '''28-day cycle for 2 to 6 cycles''' based on stage, response, and whether radiation therapy is used. | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''Retrospective:''' Savage KJ, Skinnider B, Al-Mansour M, Sehn LH, Gascoyne RD, Connors JM. Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome. Blood. 2011 Oct 27;118(17):4585-90. [ | + | # '''Retrospective:''' Savage KJ, Skinnider B, Al-Mansour M, Sehn LH, Gascoyne RD, Connors JM. Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome. Blood. 2011 Oct 27;118(17):4585-90. Epub 2011 Aug 26. [https://doi.org/10.1182/blood-2011-07-365932 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21873543/ PubMed] |
− | # '''Retrospective:''' Xing KH, Connors JM, Lai A, Al-Mansour M, Sehn LH, Villa D, Klasa R, Shenkier T, Gascoyne RD, Skinnider B, Savage KJ. Advanced-stage nodular lymphocyte predominant Hodgkin lymphoma compared with classical Hodgkin lymphoma: a matched pair outcome analysis. Blood. 2014 Jun 5;123(23):3567-73. Epub 2014 Apr 8. [ | + | # '''Retrospective:''' Xing KH, Connors JM, Lai A, Al-Mansour M, Sehn LH, Villa D, Klasa R, Shenkier T, Gascoyne RD, Skinnider B, Savage KJ. Advanced-stage nodular lymphocyte predominant Hodgkin lymphoma compared with classical Hodgkin lymphoma: a matched pair outcome analysis. Blood. 2014 Jun 5;123(23):3567-73. Epub 2014 Apr 8. [https://doi.org/10.1182/blood-2013-12-541078 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24713929/ PubMed] |
==CHOP {{#subobject:4f07a9|Regimen=1}}== | ==CHOP {{#subobject:4f07a9|Regimen=1}}== | ||
− | + | CHOP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | CHOP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>''' | ||
===Regimen {{#subobject:7bb950|Variant=1}}=== | ===Regimen {{#subobject:7bb950|Variant=1}}=== | ||
− | ''The below regimen was intended for [[Diffuse large B-cell lymphoma|DLBCL]]; no primary reference is to our knowledge available for use of CHOP in NLP-HL.'' | + | ''Note: The below regimen was intended for [[Diffuse large B-cell lymphoma|DLBCL]]; no primary reference is to our knowledge available for use of CHOP in NLP-HL.'' |
+ | <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 | + | *[[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 | ||
− | |||
'''21-day cycle for 6 to 8 cycles''' (number of cycles for CHOP in NLPHL is not well-established) | '''21-day cycle for 6 to 8 cycles''' (number of cycles for CHOP in NLPHL is not well-established) | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. [ | + | # Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. [https://doi.org/10.1200/jco.2005.09.131 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15867204/ PubMed] |
− | + | ==CVP (Vinblastine/Prednisolone) {{#subobject:55d745|Regimen=1}}== | |
− | ==CVP {{#subobject:55d745|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CVP: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''inblastine, '''<u>P</u>'''rednisolone | CVP: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''inblastine, '''<u>P</u>'''rednisolone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:8938af|Variant=1}}=== | ===Regimen {{#subobject:8938af|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | | | + | !style="width: 33%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ejca.2011.10.018 Shankar et al. 2011] |
− | |style="background-color:# | + | |2005-06 to 2010-10 |
+ | |style="background-color:#ffffbe"|Retrospective | ||
|- | |- | ||
|} | |} | ||
''Note: contrary to most CVP regimens, this one uses vinblastine, not vincristine. This regimen was used in adolescents with early stage disease; note that there is a discrepancy between the abstract and the body of the manuscript regarding number of days that prednisolone is taken for.'' | ''Note: contrary to most CVP regimens, this one uses vinblastine, not vincristine. This regimen was used in adolescents with early stage disease; note that there is a discrepancy between the abstract and the body of the manuscript regarding number of days that prednisolone is taken for.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV once per day on days 1 & 8 | *[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 8 | *[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 8 | ||
− | + | '''14- to 21-day cycle for 3 cycles''' | |
− | ''' | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | # Shankar A, Hall GW, Gorde-Grosjean S, Hasenclever D, Leblanc T, Hayward J, Lambilliotte A, Daw S, Perel Y, McCarthy K, Lejars O, Coulomb A, Oberlin WO, Wallace WH, Landman-Parker J. Treatment outcome after low intensity chemotherapy [CVP] in children and adolescents with early stage nodular lymphocyte predominant Hodgkin's lymphoma - an Anglo-French collaborative report. Eur J Cancer. 2012 Jul;48(11):1700-6. Epub 2011 Nov 15. [ | + | # '''Retrospective:''' Shankar A, Hall GW, Gorde-Grosjean S, Hasenclever D, Leblanc T, Hayward J, Lambilliotte A, Daw S, Perel Y, McCarthy K, Lejars O, Coulomb A, Oberlin WO, Wallace WH, Landman-Parker J. Treatment outcome after low intensity chemotherapy [CVP] in children and adolescents with early stage nodular lymphocyte predominant Hodgkin's lymphoma - an Anglo-French collaborative report. Eur J Cancer. 2012 Jul;48(11):1700-6. Epub 2011 Nov 15. [https://doi.org/10.1016/j.ejca.2011.10.018 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22093944/ PubMed] |
− | |||
==EPOCH {{#subobject:7022de|Regimen=1}}== | ==EPOCH {{#subobject:7022de|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 #1, Wilson et al. 1993 - original EPOCH protocol {{#subobject:1eb77a|Variant=1}}=== | + | ===Regimen variant #1, Wilson et al. 1993 - original EPOCH protocol {{#subobject:1eb77a|Variant=1}}=== |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup>/day (200 mg/m<sup>2</sup> total) IV continuous infusion on | + | *[[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>, sometimes capped at maximum total dose of 2 mg per cycle) | ||
+ | *[[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>) | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 15 minutes once on day 5 (regimen originally was day 6, but now is day 5) | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 5 (regimen originally was days 1 to 6, but now is just days 1 to 5) | *[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 5 (regimen originally was days 1 to 6, but now is just days 1 to 5) | ||
− | + | ====Supportive therapy==== | |
− | + | *PCP prophylaxis with one of the following: | |
− | + | **[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO twice per day 3 days per week | |
− | |||
− | ====Supportive | ||
− | *PCP prophylaxis | ||
− | **[[Trimethoprim | ||
**[[Atovaquone (Mepron)]] 1500 mg PO once per day | **[[Atovaquone (Mepron)]] 1500 mg PO once per day | ||
− | **[[Pentamidine (Nebupent)]] 300 mg nebulized | + | **[[Pentamidine (Nebupent)]] 300 mg nebulized once every 28 days |
− | *[[Filgrastim (Neupogen)]] 5 mcg/kg | + | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, started on day 6 and continued until ANC greater than 5000/μL past nadir |
− | |||
'''21-day cycle for 6 to 8 cycles''' | '''21-day cycle for 6 to 8 cycles''' | ||
− | + | </div></div><br> | |
− | ===Regimen #2, Wilson et al. 2002 - dose-adjusted EPOCH {{#subobject:77d453|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #2, Wilson et al. 2002 - dose-adjusted EPOCH {{#subobject:77d453|Variant=1}}=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup>/day | + | *[[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>, sometimes capped at maximum total dose of 2 mg per cycle) | |
− | *[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day (1.6 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>) |
− | *[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day (40 mg/m<sup>2</sup> | + | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 15 minutes once on day 5 |
− | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 15 minutes on day 5 | + | ====Glucocorticoid therapy==== |
− | + | *[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO twice per day on days 1 to 5 | |
− | ====Supportive | + | ====Supportive therapy==== |
− | *PCP prophylaxis | + | *PCP prophylaxis with one of the following: |
− | **[[Trimethoprim | + | **[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO twice per day 3 days per week |
**[[Atovaquone (Mepron)]] 1500 mg PO once per day | **[[Atovaquone (Mepron)]] 1500 mg PO once per day | ||
− | **[[Pentamidine (Nebupent)]] 300 mg nebulized | + | **[[Pentamidine (Nebupent)]] 300 mg nebulized once every 28 days |
− | *[[Filgrastim (Neupogen)]] 5 mcg/kg | + | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, started on day 6 and continued until ANC greater than 5000/μL past nadir |
− | |||
'''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==== | ||
*Start cycle 1 as described above | *Start cycle 1 as described above | ||
*Obtain twice per week CBCs for nadir measurements | *Obtain twice per week CBCs for nadir measurements | ||
− | *If nadir ANC greater than 500/ | + | *If nadir ANC greater than 500/μL, increase [[Etoposide (Vepesid)]], [[Doxorubicin (Adriamycin)]], and [[Cyclophosphamide (Cytoxan)]] by 20% compared to previous cycle. |
− | *If nadir ANC less than 500/ | + | *If nadir ANC less than 500/μL on 1 or 2 measurements, use same doses as last cycle |
− | *If nadir ANC less than 500/ | + | *If nadir ANC less than 500/μL on at least 3 measurements, decrease [[Etoposide (Vepesid)]], [[Doxorubicin (Adriamycin)]], and [[Cyclophosphamide (Cytoxan)]] by 20% compared to previous cycle. |
*And/or if nadir platelet count less than 25 x 10<sup>9</sup>/L on at least 1 measurement, decrease [[Etoposide (Vepesid)]], [[Doxorubicin (Adriamycin)]], and [[Cyclophosphamide (Cytoxan)]] by 20% compared to previous cycle. | *And/or if nadir platelet count less than 25 x 10<sup>9</sup>/L on at least 1 measurement, decrease [[Etoposide (Vepesid)]], [[Doxorubicin (Adriamycin)]], and [[Cyclophosphamide (Cytoxan)]] by 20% compared to previous cycle. | ||
− | *'''Dose adjustments below the cycle 1 starting dose only applies to cyclophosphamide.''' | + | *'''Dose adjustments below the cycle 1 starting dose only applies to cyclophosphamide.''' The lowest etoposide and doxorubicin would be dosed at is the original cycle 1 dose. |
− | *Can start new cycle Q21days if ANC greater than 1000/ | + | *Can start new cycle Q21days if ANC greater than 1000/μL and platelets greater than 100 x 10<sup>9</sup>/L. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start. |
− | |||
Historic dose adjustments for hematologic toxicity: | Historic dose adjustments for hematologic toxicity: | ||
These adjustments were in the original paper for standard EPOCH, which are much less relevant due to growth factor support. | These adjustments were in the original paper for standard EPOCH, which are much less relevant due to growth factor support. | ||
<br>If ANC on day 1 is: | <br>If ANC on day 1 is: | ||
− | * greater than 1500/ | + | * greater than 1500/μL, full dose cyclophosphamide |
− | * 1000 to 1500/ | + | * 1000 to 1500/μL, reduce cyclophosphamide by 187 mg/m<sup>2</sup> (equal to 25% dose reduction) |
− | * less than 1000/ | + | * less than 1000/μL, hold EPOCH |
− | *If ANC nadir is less than 500/ | + | *If ANC nadir is less than 500/μL, reduce cyclophosphamide an additional 187 mg/m<sup>2</sup> |
− | *If ANC nadir is greater than 500/ | + | *If ANC nadir is greater than 500/μL and patient had previously been dose-reduced, increase cyclophosphamide dose by 187 mg/m<sup>2</sup> |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, Kohler DR, Jaffe ES, Herdt J, Cheson BD et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J Clin Oncol. 1993 Aug;11(8):1573-82 [ | + | # Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, Kohler DR, Jaffe ES, Herdt J, Cheson BD et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J Clin Oncol. 1993 Aug;11(8):1573-82. [https://doi.org/10.1200/jco.1993.11.8.1573 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7687667/ PubMed] |
− | # Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, Steinberg SM, Little RF, Janik J, Gutierrez M, Raffeld M, Staudt L, Cheson BD, Longo DL, Harris N, Jaffe ES, Chabner BA, Wittes R, Balis F. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15;99(8):2685-93. [ | + | # Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, Steinberg SM, Little RF, Janik J, Gutierrez M, Raffeld M, Staudt L, Cheson BD, Longo DL, Harris N, Jaffe ES, Chabner BA, Wittes R, Balis F. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15;99(8):2685-93. [https://doi.org/10.1182/blood.v99.8.2685 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11929754/ PubMed] content property of [https://hemonc.org HemOnc.org] |
− | # Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, Raffeld M, Gutierrez M, Chabner BA, Staudt L, Jaffe ES, Janik JE. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008 Jun 1;26(16):2717-24. [ | + | # Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, Raffeld M, Gutierrez M, Chabner BA, Staudt L, Jaffe ES, Janik JE. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008 Jun 1;26(16):2717-24. [https://doi.org/10.1200/jco.2007.13.1391 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409217/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18378569/ PubMed] |
==R-CHOP {{#subobject:49e0e5|Regimen=1}}== | ==R-CHOP {{#subobject:49e0e5|Regimen=1}}== | ||
− | + | R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>''' | ||
===Regimen {{#subobject:2bb1cd|Variant=1}}=== | ===Regimen {{#subobject:2bb1cd|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | | | + | !style="width: 33%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578726/ Fanale et al. 2017] |
− | |style="background-color:# | + | |1995-2015 |
+ | |style="background-color:#ffffbe"|Retrospective | ||
|- | |- | ||
|} | |} | ||
''The below regimen was intended for [[Diffuse large B-cell lymphoma|DLBCL]]; to our knowledge there are no prospective trials of R-CHOP in NLP-HL.'' | ''The below regimen was intended for [[Diffuse large B-cell lymphoma|DLBCL]]; to our knowledge there are no prospective trials of R-CHOP in NLP-HL.'' | ||
+ | <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 | ||
*[[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 | + | *[[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 | ||
− | |||
'''21-day cycle for 6 to 8 cycles''' | '''21-day cycle for 6 to 8 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | <!-- # '''Retrospective Abstract:''' Fanale, Michelle A., Lai, Chao-Ming, McLaughlin, Peter, Romaguera, Jorge, Fayad, Luis, Hagemeister, Fredrick, Samaniego, Felipe, Rodriguez, Maria Alma, Neelapu, Sattva S., Shah, Jatin J, Kwak, Larry, Dong, Wenli, Reed, Valerie, Dabaja, Bouthaina S., Popat, Uday, Younes, Anas. Outcomes of Nodular Lymphocyte Predominant Hodgkin's Lymphoma (NLPHL) Patients Treated with R-CHOP. ASH Annual Meeting Abstracts 2010 116: 2812 | + | <!-- # '''Retrospective Abstract:''' Fanale, Michelle A., Lai, Chao-Ming, McLaughlin, Peter, Romaguera, Jorge, Fayad, Luis, Hagemeister, Fredrick, Samaniego, Felipe, Rodriguez, Maria Alma, Neelapu, Sattva S., Shah, Jatin J, Kwak, Larry, Dong, Wenli, Reed, Valerie, Dabaja, Bouthaina S., Popat, Uday, Younes, Anas. Outcomes of Nodular Lymphocyte Predominant Hodgkin's Lymphoma (NLPHL) Patients Treated with R-CHOP. ASH Annual Meeting Abstracts 2010 116: 2812--> |
− | # '''Retrospective:''' Fanale MA, Cheah CY, Rich A, Medeiros LJ, Lai CM, Oki Y, Romaguera JE, Fayad LE, Hagemeister FB, Samaniego F, Rodriguez MA, Neelapu SS, Lee HJ, Nastoupil L, Fowler NH, Turturro F, Westin JR, Wang ML, McLaughlin P, Pinnix CC, Milgrom SA, Dabaja B, Horowitz SB, Younes A. Encouraging activity for R-CHOP in advanced stage nodular lymphocyte-predominant Hodgkin lymphoma. Blood. 2017 Jul 27;130(4):472-477. Epub 2017 May 18. [ | + | # '''Retrospective:''' Fanale MA, Cheah CY, Rich A, Medeiros LJ, Lai CM, Oki Y, Romaguera JE, Fayad LE, Hagemeister FB, Samaniego F, Rodriguez MA, Neelapu SS, Lee HJ, Nastoupil L, Fowler NH, Turturro F, Westin JR, Wang ML, McLaughlin P, Pinnix CC, Milgrom SA, Dabaja B, Horowitz SB, Younes A. Encouraging activity for R-CHOP in advanced stage nodular lymphocyte-predominant Hodgkin lymphoma. Blood. 2017 Jul 27;130(4):472-477. Epub 2017 May 18. [https://doi.org/10.1182/blood-2017-02-766121 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578726/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28522441/ PubMed] |
− | |||
==R-CVP {{#subobject:41e37c|Regimen=1}}== | ==R-CVP {{#subobject:41e37c|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
R-CVP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone | R-CVP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:c15033|Variant=1}}=== | ===Regimen {{#subobject:c15033|Variant=1}}=== | ||
+ | <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 | ||
− | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of | + | *[[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 | ||
− | |||
'''21-day cycle for up to 8 cycles''' (number of cycles for R-CVP in NLPHL is not well-established) | '''21-day cycle for up to 8 cycles''' (number of cycles for R-CVP in NLPHL is not well-established) | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
See [[#CVP|references for CVP]] | See [[#CVP|references for CVP]] | ||
− | |||
==R-EPOCH {{#subobject:f0ac25|Regimen=1}}== | ==R-EPOCH {{#subobject:f0ac25|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) | ||
− | ===Regimen #1, Wilson et al. 1993 - original EPOCH protocol (which did not include rituximab) {{#subobject:1f818a|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, Wilson et al. 1993 - original EPOCH protocol (which did not include rituximab) {{#subobject:1f818a|Variant=1}}=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per cycle (usually given as outpatient due to reimbursement issues) | ||
====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>) |
− | *[[ | + | *[[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>, sometimes capped at maximum total dose of 2 mg per cycle) |
+ | *[[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>) | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 15 minutes once on day 5 (regimen originally was day 6, but now is day 5) | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 5 (regimen originally was days 1 to 6, but now is just days 1 to 5) | *[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 5 (regimen originally was days 1 to 6, but now is just days 1 to 5) | ||
− | + | ====Supportive therapy==== | |
− | + | *PCP prophylaxis with one of the following: | |
− | + | **[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO twice per day 3 days per week | |
− | |||
− | ====Supportive | ||
− | *PCP prophylaxis | ||
− | **[[Trimethoprim | ||
**[[Atovaquone (Mepron)]] 1500 mg PO once per day | **[[Atovaquone (Mepron)]] 1500 mg PO once per day | ||
− | **[[Pentamidine (Nebupent)]] 300 mg nebulized | + | **[[Pentamidine (Nebupent)]] 300 mg nebulized once every 28 days |
− | *[[Filgrastim (Neupogen)]] 5 mcg/kg | + | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, started on day 6 and continued until ANC greater than 5000/μL past nadir |
− | |||
'''21-day cycle for 6 to 8 cycles''' | '''21-day cycle for 6 to 8 cycles''' | ||
− | + | </div></div><br> | |
− | ===Regimen #2, Wilson et al. 2002 - dose-adjusted EPOCH {{#subobject:f46430|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #2, Wilson et al. 2002 - dose-adjusted EPOCH {{#subobject:f46430|Variant=1}}=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per cycle (usually given as outpatient due to reimbursement issues) | ||
====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 | + | *[[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>, sometimes capped at maximum total dose of 2 mg per cycle) |
− | + | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 15 minutes once on day 5 | |
− | *[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day (1.6 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>) |
− | *[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day (40 mg/m<sup>2</sup> | + | ====Glucocorticoid therapy==== |
− | *[[ | + | *[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO twice per day on days 1 to 5 |
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *PCP prophylaxis with one of the following: |
− | *PCP prophylaxis | + | **[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO twice per day 3 days per week |
− | **[[Trimethoprim | ||
**[[Atovaquone (Mepron)]] 1500 mg PO once per day | **[[Atovaquone (Mepron)]] 1500 mg PO once per day | ||
− | **[[Pentamidine (Nebupent)]] 300 mg nebulized | + | **[[Pentamidine (Nebupent)]] 300 mg nebulized once every 28 days |
− | *[[Filgrastim (Neupogen)]] 5 mcg/kg | + | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, started on day 6 and continued until ANC greater than 5000/μL past nadir |
− | |||
'''21-day cycle for 6 to 8 cycles''' | '''21-day cycle for 6 to 8 cycles''' | ||
− | + | </div> | |
− | ===Dose | + | <div class="toccolours" style="background-color:#fff2ae"> |
+ | ====Dose and schedule modifications==== | ||
*Start cycle 1 as described above | *Start cycle 1 as described above | ||
*Obtain twice per week CBCs for nadir measurements | *Obtain twice per week CBCs for nadir measurements | ||
− | *If nadir ANC greater than 500/ | + | *If nadir ANC greater than 500/μL, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle. |
− | *If nadir ANC less than 500/ | + | *If nadir ANC less than 500/μL on 1 or 2 measurements, use same doses as last cycle |
− | *If nadir ANC less than 500/ | + | *If nadir ANC less than 500/μL on at least 3 measurements, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle. |
*And/or if nadir platelet count less than 25 x 10<sup>9</sup>/L on at least 1 measurement, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle. | *And/or if nadir platelet count less than 25 x 10<sup>9</sup>/L on at least 1 measurement, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle. | ||
− | *'''Dose adjustments below the cycle 1 starting dose only applies to cyclophosphamide.''' | + | *'''Dose adjustments below the cycle 1 starting dose only applies to cyclophosphamide.''' The lowest etoposide and doxorubicin would be dosed at is the original cycle 1 dose. |
− | *Can start new cycle Q21days if ANC greater than 1000/ | + | *Can start new cycle Q21days if ANC greater than 1000/μL and platelets greater than 100 x 10<sup>9</sup>/L. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start. |
− | + | ====Dose modifications, historic dose adjustments for hematologic toxicity==== | |
− | === | ||
These adjustments were in the original paper for standard EPOCH, which are much less relevant due to growth factor support. | These adjustments were in the original paper for standard EPOCH, which are much less relevant due to growth factor support. | ||
<br>If ANC on day 1 is: | <br>If ANC on day 1 is: | ||
− | * Greater than 1500/ | + | * Greater than 1500/μL, full dose cyclophosphamide |
− | * 1000 to 1500/ | + | * 1000 to 1500/μL, reduce cyclophosphamide by 187 mg/m<sup>2</sup> (equal to 25% dose reduction) |
− | * less than 1000/ | + | * less than 1000/μL, hold EPOCH |
− | *If ANC nadir is less than 500/ | + | *If ANC nadir is less than 500/μL, reduce cyclophosphamide an additional 187 mg/m<sup>2</sup> |
− | *If ANC nadir is greater than 500/ | + | *If ANC nadir is greater than 500/μL and patient had previously been dose-reduced, increase cyclophosphamide dose by 187 mg/m<sup>2</sup> |
− | + | </div></div> | |
===References=== | ===References=== | ||
See [[#EPOCH|references for EPOCH]] | See [[#EPOCH|references for EPOCH]] | ||
− | |||
==Rituximab monotherapy {{#subobject:be5153|Regimen=1}}== | ==Rituximab monotherapy {{#subobject:be5153|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:c26f73|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood.v101.2.420 Rehwald et al. 2003] |
− | | | + | |1999-2002 |
− | + | |style="background-color:#91cf61"|Phase 2 | |
− | |||
− | |||
− | | | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2002-08-2644 Ekstrand et al. 2003] |
− | |style="background-color:# | + | |1999-2002 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2013.53.2069 Advani et al. 2014 (U2082N)] |
− | |style="background-color:# | + | |1999-2006 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2011-06-361055 Eichenauer et al. 2011 (GHSG RIPL)] |
− | |style="background-color:# | + | |2006-2007 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per week | + | ====Targeted therapy==== |
+ | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Acetaminophen (Tylenol)]] 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to rituximab | ||
+ | *[[Diphenhydramine (Benadryl)]] 25 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to rituximab | ||
+ | '''4-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *U2082N, after protocol amendment: [[#Rituximab_monotherapy_2|Rituximab]] maintenance | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Rehwald U, Schulz H, Reiser M, Sieber M, Staak JO, Morschhauser F, Driessen C, Rudiger T, Muller-Hermelink K, Diehl V, Engert A; German Hodgkin Lymphoma Study Group (GHSG). Treatment of relapsed CD20+ Hodgkin lymphoma with the monoclonal antibody rituximab is effective and well tolerated: results of a phase 2 trial of the German Hodgkin Lymphoma Study Group. Blood. 2003 Jan 15;101(2):420-4. [https://doi.org/10.1182/blood.v101.2.420 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12509381/ PubMed] | ||
+ | ## '''Update:''' Schulz H, Rehwald U, Morschhauser F, Elter T, Driessen C, Rüdiger T, Borchmann P, Schnell R, Diehl V, Engert A, Reiser M. Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG). Blood. 2008 Jan 1;111(1):109-11. Epub 2007 Oct 15. [https://doi.org/10.1182/blood-2007-03-078725 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17938252/ PubMed] | ||
+ | # Ekstrand BC, Lucas JB, Horwitz SM, Fan Z, Breslin S, Hoppe RT, Natkunam Y, Bartlett NL, Horning SJ. Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial. Blood. 2003 Jun 1;101(11):4285-9. Epub 2003 Feb 13. [https://doi.org/10.1182/blood-2002-08-2644 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12586628/ PubMed] | ||
+ | # '''GHSG RIPL:''' Eichenauer DA, Fuchs M, Pluetschow A, Klimm B, Halbsguth T, Böll B, von Tresckow B, Nogová L, Borchmann P, Engert A. Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood. 2011 Oct 20;118(16):4363-5. Epub 2011 Aug 9. [https://doi.org/10.1182/blood-2011-06-361055 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21828141/ PubMed] [https://clinicaltrials.gov/study/NCT00346684 NCT00346684] | ||
+ | <!-- Presented in part at the 49th Annual Meeting of the American Society of Hematology (ASH), Atlanta, GA, December 8-11, 2007, and 53rd Annual Meeting of ASH, San Diego, CA, December 10-13, 2011. --> | ||
+ | # '''U2082N:''' Advani RH, Horning SJ, Hoppe RT, Daadi S, Allen J, Natkunam Y, Bartlett NL. Mature results of a phase II study of rituximab therapy for nodular lymphocyte-predominant Hodgkin lymphoma. J Clin Oncol. 2014 Mar 20;32(9):912-8. Epub 2014 Feb 10. [https://doi.org/10.1200/jco.2013.53.2069 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24516013/ PubMed] [https://clinicaltrials.gov/study/NCT00003820 NCT00003820] | ||
− | ==== | + | =Maintenance after upfront therapy= |
− | + | ==Rituximab monotherapy {{#subobject:8353c7|Regimen=1}}== | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:587056|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | + | !style="width: 33%"|Study | |
− | ===Regimen | + | !style="width: 33%"|Dates of enrollment |
− | {| class="wikitable" style="width: | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2013.53.2069 Advani et al. 2014 (U2082N)] |
− | |style="background-color:# | + | |1999-2006 |
+ | |style="background-color:#ffffbe"|Phase 2, fewer than 20 patients in this arm | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[Rituximab | + | ====Preceding treatment==== |
− | + | *[[#Rituximab_monotherapy|Rituximab]] induction x 4 | |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per | + | ====Targeted therapy==== |
− | + | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | |
− | ''' | + | '''6-month cycle for 4 cycles (2 years)''' |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | |||
− | |||
− | |||
− | |||
<!-- Presented in part at the 49th Annual Meeting of the American Society of Hematology (ASH), Atlanta, GA, December 8-11, 2007, and 53rd Annual Meeting of ASH, San Diego, CA, December 10-13, 2011. --> | <!-- Presented in part at the 49th Annual Meeting of the American Society of Hematology (ASH), Atlanta, GA, December 8-11, 2007, and 53rd Annual Meeting of ASH, San Diego, CA, December 10-13, 2011. --> | ||
− | # Advani RH, Horning SJ, Hoppe RT, Daadi S, Allen J, Natkunam Y, Bartlett NL. Mature | + | # '''U2082N:''' Advani RH, Horning SJ, Hoppe RT, Daadi S, Allen J, Natkunam Y, Bartlett NL. Mature results of a phase II study of rituximab therapy for nodular lymphocyte-predominant Hodgkin lymphoma. J Clin Oncol. 2014 Mar 20;32(9):912-8. Epub 2014 Feb 10. [https://doi.org/10.1200/jco.2013.53.2069 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24516013/ PubMed] [https://clinicaltrials.gov/study/NCT00003820 NCT00003820] |
− | |||
[[Category:Hodgkin lymphoma, nodular lymphocyte-predominant regimens]] | [[Category:Hodgkin lymphoma, nodular lymphocyte-predominant regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Indolent lymphomas]] | [[Category:Indolent lymphomas]] |
Latest revision as of 23:38, 15 July 2024
Section editor | |
---|---|
Sanjai Sharma, MD Sequoia Regional Cancer Center Visalia, CA, USA |
This page contains histology-specific studies. For the more general classical Hodgkin lymphoma page, follow this link.
- We have moved How I Treat articles to a dedicated page.
9 regimens on this page
11 variants on this page
|
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.
JCO "Oncology Grand Rounds"
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Hodgkin Lymphoma.
Untreated
ABVD
ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Savage et al. 2011 | 1966-02 to 2009-05 | Retrospective |
Xing et al. 2014 | 1970-2011 | Retrospective |
Note: there are some reports of using rituximab although schedule & number of cycles is not well-established.
Chemotherapy
- Doxorubicin (Adriamycin) 25 mg/m2 IV once per day on days 1 & 15
- Bleomycin (Blenoxane) 10 units/m2 IV once per day on days 1 & 15 (1 unit test dose with cycle 1 doses, 60 minutes prior to remainder of full dose)
- Vinblastine (Velban) 6 mg/m2 IV once per day on days 1 & 15
- Dacarbazine (DTIC) 375 mg/m2 IV once per day on days 1 & 15
28-day cycle for 2 to 6 cycles based on stage, response, and whether radiation therapy is used.
References
- Retrospective: Savage KJ, Skinnider B, Al-Mansour M, Sehn LH, Gascoyne RD, Connors JM. Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome. Blood. 2011 Oct 27;118(17):4585-90. Epub 2011 Aug 26. link to original article PubMed
- Retrospective: Xing KH, Connors JM, Lai A, Al-Mansour M, Sehn LH, Villa D, Klasa R, Shenkier T, Gascoyne RD, Skinnider B, Savage KJ. Advanced-stage nodular lymphocyte predominant Hodgkin lymphoma compared with classical Hodgkin lymphoma: a matched pair outcome analysis. Blood. 2014 Jun 5;123(23):3567-73. Epub 2014 Apr 8. link to original article PubMed
CHOP
CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne
Regimen
Note: The below regimen was intended for DLBCL; no primary reference is to our knowledge available for use of CHOP in NLP-HL.
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
21-day cycle for 6 to 8 cycles (number of cycles for CHOP in NLPHL is not well-established)
References
- Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. link to original article dosing details in abstract have been reviewed by our editors PubMed
CVP (Vinblastine/Prednisolone)
CVP: Cyclophosphamide, Vinblastine, Prednisolone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Shankar et al. 2011 | 2005-06 to 2010-10 | Retrospective |
Note: contrary to most CVP regimens, this one uses vinblastine, not vincristine. This regimen was used in adolescents with early stage disease; note that there is a discrepancy between the abstract and the body of the manuscript regarding number of days that prednisolone is taken for.
Chemotherapy
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
- Vinblastine (Velban) 6 mg/m2 IV once per day on days 1 & 8
Glucocorticoid therapy
- Prednisolone (Millipred) 40 mg/m2 PO once per day on days 1 to 8
14- to 21-day cycle for 3 cycles
References
- Retrospective: Shankar A, Hall GW, Gorde-Grosjean S, Hasenclever D, Leblanc T, Hayward J, Lambilliotte A, Daw S, Perel Y, McCarthy K, Lejars O, Coulomb A, Oberlin WO, Wallace WH, Landman-Parker J. Treatment outcome after low intensity chemotherapy [CVP] in children and adolescents with early stage nodular lymphocyte predominant Hodgkin's lymphoma - an Anglo-French collaborative report. Eur J Cancer. 2012 Jul;48(11):1700-6. Epub 2011 Nov 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed
EPOCH
EPOCH: Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
Regimen variant #1, Wilson et al. 1993 - original EPOCH protocol
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, sometimes capped at maximum total dose of 2 mg per cycle)
- Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 5 (regimen originally was day 6, but now is day 5)
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 5 (regimen originally was days 1 to 6, but now is just days 1 to 5)
Supportive therapy
- PCP prophylaxis with one of the following:
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day 3 days per week
- Atovaquone (Mepron) 1500 mg PO once per day
- Pentamidine (Nebupent) 300 mg nebulized once every 28 days
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, started on day 6 and continued until ANC greater than 5000/μL past nadir
21-day cycle for 6 to 8 cycles
Regimen variant #2, Wilson et al. 2002 - dose-adjusted EPOCH
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, sometimes capped at maximum total dose of 2 mg per cycle)
- Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 5
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 PO twice per day on days 1 to 5
Supportive therapy
- PCP prophylaxis with one of the following:
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day 3 days per week
- Atovaquone (Mepron) 1500 mg PO once per day
- Pentamidine (Nebupent) 300 mg nebulized once every 28 days
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, started on day 6 and continued until ANC greater than 5000/μL past nadir
21-day cycle for 6 to 8 cycles
Dose and schedule modifications
- Start cycle 1 as described above
- Obtain twice per week CBCs for nadir measurements
- If nadir ANC greater than 500/μL, increase Etoposide (Vepesid), Doxorubicin (Adriamycin), and Cyclophosphamide (Cytoxan) by 20% compared to previous cycle.
- If nadir ANC less than 500/μL on 1 or 2 measurements, use same doses as last cycle
- If nadir ANC less than 500/μL on at least 3 measurements, decrease Etoposide (Vepesid), Doxorubicin (Adriamycin), and Cyclophosphamide (Cytoxan) by 20% compared to previous cycle.
- And/or if nadir platelet count less than 25 x 109/L on at least 1 measurement, decrease Etoposide (Vepesid), Doxorubicin (Adriamycin), and Cyclophosphamide (Cytoxan) by 20% compared to previous cycle.
- Dose adjustments below the cycle 1 starting dose only applies to cyclophosphamide. The lowest etoposide and doxorubicin would be dosed at is the original cycle 1 dose.
- Can start new cycle Q21days if ANC greater than 1000/μL and platelets greater than 100 x 109/L. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.
Historic dose adjustments for hematologic toxicity:
These adjustments were in the original paper for standard EPOCH, which are much less relevant due to growth factor support.
If ANC on day 1 is:
- greater than 1500/μL, full dose cyclophosphamide
- 1000 to 1500/μL, reduce cyclophosphamide by 187 mg/m2 (equal to 25% dose reduction)
- less than 1000/μL, hold EPOCH
- If ANC nadir is less than 500/μL, reduce cyclophosphamide an additional 187 mg/m2
- If ANC nadir is greater than 500/μL and patient had previously been dose-reduced, increase cyclophosphamide dose by 187 mg/m2
References
- Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, Kohler DR, Jaffe ES, Herdt J, Cheson BD et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J Clin Oncol. 1993 Aug;11(8):1573-82. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, Steinberg SM, Little RF, Janik J, Gutierrez M, Raffeld M, Staudt L, Cheson BD, Longo DL, Harris N, Jaffe ES, Chabner BA, Wittes R, Balis F. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15;99(8):2685-93. link to original article dosing details in abstract have been reviewed by our editors PubMed content property of HemOnc.org
- Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, Raffeld M, Gutierrez M, Chabner BA, Staudt L, Jaffe ES, Janik JE. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008 Jun 1;26(16):2717-24. link to original article link to PMC article PubMed
R-CHOP
R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Fanale et al. 2017 | 1995-2015 | Retrospective |
The below regimen was intended for DLBCL; to our knowledge there are no prospective trials of R-CHOP in NLP-HL.
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (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
21-day cycle for 6 to 8 cycles
References
- Retrospective: Fanale MA, Cheah CY, Rich A, Medeiros LJ, Lai CM, Oki Y, Romaguera JE, Fayad LE, Hagemeister FB, Samaniego F, Rodriguez MA, Neelapu SS, Lee HJ, Nastoupil L, Fowler NH, Turturro F, Westin JR, Wang ML, McLaughlin P, Pinnix CC, Milgrom SA, Dabaja B, Horowitz SB, Younes A. Encouraging activity for R-CHOP in advanced stage nodular lymphocyte-predominant Hodgkin lymphoma. Blood. 2017 Jul 27;130(4):472-477. Epub 2017 May 18. link to original article link to PMC article PubMed
R-CVP
R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone
Regimen
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 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
21-day cycle for up to 8 cycles (number of cycles for R-CVP in NLPHL is not well-established)
References
R-EPOCH
R-EPOCH: Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
Regimen variant #1, Wilson et al. 1993 - original EPOCH protocol (which did not include rituximab)
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once per cycle (usually given as outpatient due to reimbursement issues)
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, sometimes capped at maximum total dose of 2 mg per cycle)
- Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 5 (regimen originally was day 6, but now is day 5)
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 5 (regimen originally was days 1 to 6, but now is just days 1 to 5)
Supportive therapy
- PCP prophylaxis with one of the following:
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day 3 days per week
- Atovaquone (Mepron) 1500 mg PO once per day
- Pentamidine (Nebupent) 300 mg nebulized once every 28 days
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, started on day 6 and continued until ANC greater than 5000/μL past nadir
21-day cycle for 6 to 8 cycles
Regimen variant #2, Wilson et al. 2002 - dose-adjusted EPOCH
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once per cycle (usually given as outpatient due to reimbursement issues)
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, sometimes capped at maximum total dose of 2 mg per cycle)
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 5
- Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
Glucocorticoid therapy
- Prednisone (Sterapred) 60 mg/m2 PO twice per day on days 1 to 5
Supportive therapy
- PCP prophylaxis with one of the following:
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day 3 days per week
- Atovaquone (Mepron) 1500 mg PO once per day
- Pentamidine (Nebupent) 300 mg nebulized once every 28 days
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, started on day 6 and continued until ANC greater than 5000/μL past nadir
21-day cycle for 6 to 8 cycles
Dose and schedule modifications
- Start cycle 1 as described above
- Obtain twice per week CBCs for nadir measurements
- If nadir ANC greater than 500/μL, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
- If nadir ANC less than 500/μL on 1 or 2 measurements, use same doses as last cycle
- If nadir ANC less than 500/μL on at least 3 measurements, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
- And/or if nadir platelet count less than 25 x 109/L on at least 1 measurement, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
- Dose adjustments below the cycle 1 starting dose only applies to cyclophosphamide. The lowest etoposide and doxorubicin would be dosed at is the original cycle 1 dose.
- Can start new cycle Q21days if ANC greater than 1000/μL and platelets greater than 100 x 109/L. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.
Dose modifications, historic dose adjustments for hematologic toxicity
These adjustments were in the original paper for standard EPOCH, which are much less relevant due to growth factor support.
If ANC on day 1 is:
- Greater than 1500/μL, full dose cyclophosphamide
- 1000 to 1500/μL, reduce cyclophosphamide by 187 mg/m2 (equal to 25% dose reduction)
- less than 1000/μL, hold EPOCH
- If ANC nadir is less than 500/μL, reduce cyclophosphamide an additional 187 mg/m2
- If ANC nadir is greater than 500/μL and patient had previously been dose-reduced, increase cyclophosphamide dose by 187 mg/m2
References
Rituximab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Rehwald et al. 2003 | 1999-2002 | Phase 2 |
Ekstrand et al. 2003 | 1999-2002 | Phase 2 |
Advani et al. 2014 (U2082N) | 1999-2006 | Phase 2 |
Eichenauer et al. 2011 (GHSG RIPL) | 2006-2007 | Phase 2 |
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days 1, 8, 15, 22
Supportive therapy
- Acetaminophen (Tylenol) 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to rituximab
- Diphenhydramine (Benadryl) 25 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to rituximab
4-week course
Subsequent treatment
- U2082N, after protocol amendment: Rituximab maintenance
References
- Rehwald U, Schulz H, Reiser M, Sieber M, Staak JO, Morschhauser F, Driessen C, Rudiger T, Muller-Hermelink K, Diehl V, Engert A; German Hodgkin Lymphoma Study Group (GHSG). Treatment of relapsed CD20+ Hodgkin lymphoma with the monoclonal antibody rituximab is effective and well tolerated: results of a phase 2 trial of the German Hodgkin Lymphoma Study Group. Blood. 2003 Jan 15;101(2):420-4. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Schulz H, Rehwald U, Morschhauser F, Elter T, Driessen C, Rüdiger T, Borchmann P, Schnell R, Diehl V, Engert A, Reiser M. Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG). Blood. 2008 Jan 1;111(1):109-11. Epub 2007 Oct 15. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Ekstrand BC, Lucas JB, Horwitz SM, Fan Z, Breslin S, Hoppe RT, Natkunam Y, Bartlett NL, Horning SJ. Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial. Blood. 2003 Jun 1;101(11):4285-9. Epub 2003 Feb 13. link to original article dosing details in abstract have been reviewed by our editors PubMed
- GHSG RIPL: Eichenauer DA, Fuchs M, Pluetschow A, Klimm B, Halbsguth T, Böll B, von Tresckow B, Nogová L, Borchmann P, Engert A. Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood. 2011 Oct 20;118(16):4363-5. Epub 2011 Aug 9. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00346684
- U2082N: Advani RH, Horning SJ, Hoppe RT, Daadi S, Allen J, Natkunam Y, Bartlett NL. Mature results of a phase II study of rituximab therapy for nodular lymphocyte-predominant Hodgkin lymphoma. J Clin Oncol. 2014 Mar 20;32(9):912-8. Epub 2014 Feb 10. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003820
Maintenance after upfront therapy
Rituximab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Advani et al. 2014 (U2082N) | 1999-2006 | Phase 2, fewer than 20 patients in this arm |
Preceding treatment
- Rituximab induction x 4
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days 1, 8, 15, 22
6-month cycle for 4 cycles (2 years)
References
- U2082N: Advani RH, Horning SJ, Hoppe RT, Daadi S, Allen J, Natkunam Y, Bartlett NL. Mature results of a phase II study of rituximab therapy for nodular lymphocyte-predominant Hodgkin lymphoma. J Clin Oncol. 2014 Mar 20;32(9):912-8. Epub 2014 Feb 10. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003820