Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? Please go to the [[Follicular_lymphoma|main follicular lymphoma regimen page]] to find other regimens.
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|-
 
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|<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: #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>
 
−
|}
 
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{{TOC limit|limit=3}}
 
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''Note: Some of these regimens are not specific to follicular lymphoma because they were published before the modern classification schema was finalized. That said, most indolent lymphomas are follicular lymphoma and unless otherwise specified these should be assumed to be germane to follicular lymphoma.''
 
−
=First-line therapy=
 
−
==CHOP {{#subobject:39e6ac|Regimen=1}}==
 
−
CHOP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, capped vincristine {{#subobject:d78eb4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://doi.org/10.1002/cncr.22093 Nickenig et al. 2006 (GLSG '96)]
 
−
|1996-1998
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#MCP|MCP]]
 
−
|style="background-color:#d9ef8b"|Might have superior CR rate
 
−
|-
 
−
|[http://www.bloodjournal.org/content/106/12/3725.long Hiddemann et al. 2005 (GLSG '00)]
 
−
|2000-2003
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Follicular_lymphoma#R-CHOP|R-CHOP]]
 
−
|style="background-color:#d73027"|Inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for 6 to 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, uncapped vincristine {{#subobject:22ca16|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://doi.org/10.1200/jco.2004.07.170 Zinzani et al. 2004]
 
−
|1999-2002
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#FM|FM]]
 
−
|style="background-color:#d73027"|Inferior CR rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> 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 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with PR or CR with detectable bcl-2/IgH fusion by PCR: [[Follicular_lymphoma#Rituximab_monotherapy.2C_abbreviated_course|R]] x 4
 
−
</div></div>
 
−
===References===
 
−
# Zinzani PL, Pulsoni A, Perrotti A, Soverini S, Zaja F, De Renzo A, Storti S, Lauta VM, Guardigni L, Gentilini P, Tucci A, Molinari AL, Gobbi M, Falini B, Fattori PP, Ciccone F, Alinari L, Martelli M, Pileri S, Tura S, Baccarani M. Fludarabine plus mitoxantrone with and without rituximab versus CHOP with and without rituximab as front-line treatment for patients with follicular lymphoma. J Clin Oncol. 2004 Jul 1;22(13):2654-61. Epub 2004 May 24. [https://doi.org/10.1200/jco.2004.07.170 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15159414 PubMed]
 
−
# '''GLSG '00:''' Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, Reiser M, Metzner B, Harder H, Hegewisch-Becker S, Fischer T, Kropff M, Reis HE, Freund M, Wörmann B, Fuchs R, Planker M, Schimke J, Eimermacher H, Trümper L, Aldaoud A, Parwaresch R, Unterhalt M. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005 Dec 1;106(12):3725-32. Epub 2005 Aug 25. [http://www.bloodjournal.org/content/106/12/3725.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16123223 PubMed]
 
−
# '''GELA GELF-94:''' Sebban C, Mounier N, Brousse N, Belanger C, Brice P, Haioun C, Tilly H, Feugier P, Bouabdallah R, Doyen C, Salles G, Coiffier B. Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA). Blood. 2006 Oct 15;108(8):2540-4. Epub 2006 Jul 11. [http://www.bloodjournal.org/content/108/8/2540.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/16835383 PubMed] NCT00140569
 
−
# '''GLSG '96:''' Nickenig C, Dreyling M, Hoster E, Pfreundschuh M, Trumper L, Reiser M, Wandt H, Lengfelder E, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. Combined cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) improves response rates but not survival and has lower hematologic toxicity compared with combined mitoxantrone, chlorambucil, and prednisone (MCP) in follicular and mantle cell lymphomas: results of a prospective randomized trial of the German Low-Grade Lymphoma Study Group. Cancer. 2006 Sep 1;107(5):1014-22. [https://doi.org/10.1002/cncr.22093 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16878325 PubMed]
 
−
==CHOP-B {{#subobject:bb947|Regimen=1}}==
 
−
CHOP-B: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne, '''<u>B</u>'''leomycin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4f9502|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://doi.org/10.1200/jco.2003.05.128 Peterson et al. 2003 (CALGB 7951)]
 
−
|1980-1985
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[Follicular_lymphoma#Cyclophosphamide_monotherapy|Cyclophosphamide]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
*[[Bleomycin (Blenoxane)]] as follows:
 
−
**Cycles 1 to 6: 10 units/m<sup>2</sup> IM once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for 6 cycles, then 28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''CALGB 7951:''' Peterson BA, Petroni GR, Frizzera G, Barcos M, Bloomfield CD, Nissen NI, Hurd DD, Henderson ES, Sartiano GP, Johnson JL, Holland JF, Gottlieb AJ. Prolonged single-agent versus combination chemotherapy in indolent follicular lymphomas: a study of the Cancer and Leukemia Group B. J Clin Oncol. 2003 Jan 1;21(1):5-15. [https://doi.org/10.1200/jco.2003.05.128 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12506163 PubMed]
 
−
==CHOP, then <sup>131</sup>Iodine-Tositumomab {{#subobject:57fff5|Regimen=1}}==
 
−
CHOP-RIT: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne '''<u>R</u>'''adio'''<u>I</u>'''mmuno'''<u>T</u>'''herapy
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:8c52b8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/102/5/1606.long Press et al. 2003 (SWOG S9911)]
 
−
|1999-2000
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732010/ Press et al. 2012 (SWOG S0016)]
 
−
|2001-2008
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 
−
|[[Follicular_lymphoma#R-CHOP|R-CHOP]]
 
−
| style="background-color:#1a9850" |Superior PFS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for SWOG S0016 is based on the 2018 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, CHOP portion====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy, CHOP portion====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[Allopurinol (Zyloprim)]] 300 mg PO once per day for patients with bulky disease
 
−
'''21-day cycle for 6 cycles, followed by:'''
 
−
====Radioconjugate therapy, dosimetric step====
 
−
*On Day 1, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with 5 mCi of Iodine-131]] IV over 20 minutes
 
−
**First scan of whole body dosimetry & redistribution within 1 hour of finishing dosimetric dose on day 1
 
−
*Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
 
−
*Day 6 or 7: Third scan of whole body dosimetry & redistribution
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO three times per day, Lugol solution 20 drops PO three times per day, or potassium iodide tablets 130 mg PO once per day, starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion
 
−
====Radioconjugate therapy, therapeutic step====
 
−
*Any one day 7 to 14 days after dosimetric infusion, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour, given first
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body]] IV over 20 minutes
 
−
***65 cGy total body dose used for patients with platelet counts of 100 to 150,000/mm3
 
−
''Calculated dose of I-131 is based on information from serial total-body gamma-camera counts''
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO three times per day, Lugol solution 20 drops PO three times per day, or potassium iodide tablets 130 mg PO once per day, starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion
 
−
</div></div>
 
−
===References===
 
−
# '''SWOG S9911:''' Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, LeBlanc M, Gaynor ER, Rivkin SE, Fisher RI. A phase 2 trial of CHOP chemotherapy followed by tositumomab/iodine I 131 tositumomab for previously untreated follicular non-Hodgkin lymphoma: Southwest Oncology Group Protocol S9911. Blood. 2003 Sep 1;102(5):1606-12. Epub 2003 May 8. [http://www.bloodjournal.org/content/102/5/1606.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12738671 PubMed] NCT00003784
 
−
## '''Update:''' Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, Leblanc M, Fisher RI; [[Study_Groups#SWOG|SWOG]]. Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin's lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911. J Clin Oncol. 2006 Sep 1;24(25):4143-9. Epub 2006 Aug 8. [https://doi.org/10.1200/jco.2006.05.8198 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16896003 PubMed]
 
−
# '''SWOG S0016:''' Press OW, Unger JM, Rimsza LM, Friedberg JW, LeBlanc M, Czuczman MS, Kaminski M, Braziel RM, Spier C, Gopal AK, Maloney DG, Cheson BD, Dakhil SR, Miller TP, Fisher RI. Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus 131Iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016. J Clin Oncol. 2013 Jan 20;31(3):314-20. Epub 2012 Dec 10. [https://doi.org/10.1200/jco.2012.42.4101 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23233710 PubMed] NCT00006721
 
−
## '''Update:''' Shadman M, Li H, Rimsza L, Leonard JP, Kaminski MS, Braziel RM, Spier CM, Gopal AK, Maloney DG, Cheson BD, Dakhil S, LeBlanc M, Smith SM, Fisher RI, Friedberg JW, Press OW. Continued excellent outcomes in previously untreated patients with follicular lymphoma after treatment with CHOP plus rituximab or CHOP plus (131)I-tositumomab: long-term follow-up of phase III randomized study SWOG-S0016. J Clin Oncol. 2018 Mar 1;36(7):697-703. Epub 2018 Jan 22. [https://doi.org/10.1200/JCO.2017.74.5083 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29356608 PubMed]
 
−
==CHVP {{#subobject:4dd34a|Regimen=1}}==
 
−
CHVP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>V</u>'''umon (Teniposide), '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bb6c6f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://doi.org/10.1056/NEJM199311253292203 Solal-Celigny et al. 1993 (GELA GELF-86)]
 
−
|1986-1991
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#CHVP-I|CHVP-I]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Teniposide (Vumon)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''1-month cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*SD or better: [[#CHVP_88|CHVP]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# '''GELA GELF-86:''' Solal-Celigny P, Lepage E, Brousse N, Reyes F, Haioun C, Leporrier M, Peuchmaur M, Bosly A, Parlier Y, Brice P, Coiffier B, Gisselbrecht C; Groupe d'Etude des Lymphomes de l'Adulte. Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. N Engl J Med. 1993 Nov 25;329(22):1608-14. [https://doi.org/10.1056/NEJM199311253292203 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8232429 PubMed]
 
−
==CHVP-I {{#subobject:b8f655|Regimen=1}}==
 
−
CHVP-I: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>V</u>'''umon (Teniposide), '''<u>P</u>'''rednisone, '''<u>I</u>'''nterferon alfa-2b
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:697b4f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://doi.org/10.1056/NEJM199311253292203 Solal-Celigny et al. 1993 (GELA GELF-86)]
 
−
|1986-1991
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[#CHVP|CHVP]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[http://www.bloodjournal.org/content/105/10/3817.long Deconinck et al. 2005 (GOELAMS 064)]
 
−
|1994-2001
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#VCAP_88|VCAP]], then HDT
 
−
| style="background-color:#fc8d59" |Seems to have inferior EFS
 
−
|-
 
−
|[http://www.bloodjournal.org/content/108/8/2540.long Sebban et al. 2006 (GELA GELF-94)]
 
−
|1994-2001
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#CHOP|CHOP]], then HDT
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Teniposide (Vumon)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]]
 
−
====Immunotherapy====
 
−
*[[Interferon alfa-2b (Intron-A)]]
 
−
</div></div>
 
−
===References===
 
−
# '''GELA GELF-86:''' Solal-Celigny P, Lepage E, Brousse N, Reyes F, Haioun C, Leporrier M, Peuchmaur M, Bosly A, Parlier Y, Brice P, Coiffier B, Gisselbrecht C; Groupe d'Etude des Lymphomes de l'Adulte. Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. N Engl J Med. 1993 Nov 25;329(22):1608-14. [https://doi.org/10.1056/NEJM199311253292203 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8232429 PubMed]
 
−
# '''GOELAMS 064:''' Deconinck E, Foussard C, Milpied N, Bertrand P, Michenet P, Cornillet-LeFebvre P, Escoffre-Barbe M, Maisonneuve H, Delwail V, Gressin R, Legouffe E, Vilque JP, Desablens B, Jaubert J, Ramee JF, Jenabian A, Thyss A, Le Pourhiet-Le Mevel A, Travade P, Delepine R, Colombat P; GOELAMS. High-dose therapy followed by autologous purged stem-cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by GOELAMS. Blood. 2005 May 15;105(10):3817-23. Epub 2005 Feb 1. [http://www.bloodjournal.org/content/105/10/3817.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/15687232 PubMed] NCT00696735
 
−
##'''Update:''' Gyan E, Foussard C, Bertrand P, Michenet P, Le Gouill S, Berthou C, Maisonneuve H, Delwail V, Gressin R, Quittet P, Vilque JP, Desablens B, Jaubert J, Ramée JF, Arakelyan N, Thyss A, Moluçon-Chabrot C, Delépine R, Milpied N, Colombat P, Deconinck E; Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang (GOELAMS). High-dose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by the GOELAMS with final results after a median follow-up of 9 years. Blood. 2009 Jan 29;113(5):995-1001. Epub 2008 Oct 27. [https://doi.org/10.1182/blood-2008-05-160200 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18955565/ PubMed]
 
−
# '''GELA GELF-94:''' Sebban C, Mounier N, Brousse N, Belanger C, Brice P, Haioun C, Tilly H, Feugier P, Bouabdallah R, Doyen C, Salles G, Coiffier B. Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA). Blood. 2006 Oct 15;108(8):2540-4. Epub 2006 Jul 11. [http://www.bloodjournal.org/content/108/8/2540.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/16835383 PubMed] NCT00140569
 
−
==COPA {{#subobject:5d3856|Regimen=1}}==
 
−
COPA: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:2a4d8d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://doi.org/10.1200/JCO.1987.5.9.1329 O'Connell et al. 1987]
 
−
|1978-1983
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[#COPA-B_88|COPA-B]]<br>2. [[#CAP-BOP_88|CAP-BOP]]
 
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199211053271902 Smalley et al. 1992]
 
−
|1985-1988
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#I-COPA_88|I-COPA]]
 
−
| style="background-color:#d73027" |Inferior TTTF
 
−
|-
 
−
|}
 
−
''Note: this regimen is very similar but distinct from CHOP. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''28-day cycle for 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# O'Connell MJ, Harrington DP, Earle JD, Johnson GJ, Glick JH, Carbone PP, Creech RH, Neiman RS, Mann RB, Silverstein MN. Prospectively randomized clinical trial of three intensive chemotherapy regimens for the treatment of advanced unfavorable histology non-Hodgkin's lymphoma. J Clin Oncol. 1987 Sep;5(9):1329-39. [https://doi.org/10.1200/JCO.1987.5.9.1329 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2442322 PubMed]
 
−
# Smalley RV, Andersen JW, Hawkins MJ, Bhide V, O'Connell MJ, Oken MM, Borden EC. Interferon alfa combined with cytotoxic chemotherapy for patients with non-Hodgkin's lymphoma. N Engl J Med. 1992 Nov 5;327(19):1336-41. [https://doi.org/10.1056/NEJM199211053271902 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1406835 PubMed]
 
−
==CVP {{#subobject:85625d|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
 
−
<br>VCP: '''<u>V</u>'''incristine, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 750/1.4/40 {{#subobject:dfc019|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.03.7952 Hagenbeek et al. 2006]
 
−
|1993-1997
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Fludarabine_monotherapy|Fludarabine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS48
 
−
| style="background-color:#1a9850" |Less toxic
 
−
|-
 
−
|[http://www.bloodjournal.org/content/105/4/1417.full Marcus et al. 2004]
 
−
|2000-2002
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Follicular_lymphoma#R-CVP|R-CVP]]
 
−
|style="background-color:#d73027"|Inferior TTP
 
−
|style="background-color:#91cf61"|Similar toxicity
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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 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
 
−
'''21-day cycle for up to 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 1000/1.4/100 {{#subobject:cb6f9b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/PMC2668968/ Hochster et al. 2009 (ECOG E1496)]
 
−
|NR
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#FC|FC]]
 
−
|style="background-color:#d3d3d3"|Not reported
 
−
|-
 
−
|}
 
−
''Note: the FC arm was closed prematurely and comparisons between CVP and FC were not conducted.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 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
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for 6 to 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Follicular_lymphoma#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance versus [[Follicular_lymphoma#Observation_2|observation]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 2000/1.4/100 {{#subobject:24f33f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://pubmed.ncbi.nlm.nih.gov/8656680 Unterhalt et al. 1996]
 
−
|NR in abstract
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#PmM_88|PmM]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> (route not specified) once per day on days 1 to 5
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> (route not specified) once per day on days 1 to 5
 
−
'''21-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders: [[#CVP|COP]] x 2 (8 total), then [[#Interferon_alfa-2a_monotherapy|interferon alfa]] maintenance versus [[Follicular_lymphoma#Observation_2|observation]]
 
−
</div></div>
 
−
===References===
 
−
# Unterhalt M, Herrmann R, Tiemann M, Parwaresch R, Stein H, Trümper L, Nahler M, Reuss-Borst M, Tirier C, Neubauer A, Freund M, Kreuser ED, Dietzfelbinger H, Bodenstein H, Engert A, Stauder R, Eimermacher H, Landys K, Hiddemann W; German Low-Grade Lymphoma Study Group. Prednimustine, mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) for the treatment of advanced low-grade non-Hodgkin's lymphoma. Leukemia. 1996 May;10(5):836-43. [https://pubmed.ncbi.nlm.nih.gov/8656680 PubMed]
 
−
## '''Update:''' Hiddemann W, Unterhalt M, Herrmann R, Wöltjen HH, Kreuser ED, Trümper L, Reuss-Borst M, Terhardt-Kasten E, Busch M, Neubauer A, Kaiser U, Hanrath RD, Middeke H, Helm G, Freund M, Stein H, Tiemann M, Parwaresch R. Mantle-cell lymphomas have more widespread disease and a slower response to chemotherapy compared with follicle-center lymphomas: results of a prospective comparative analysis of the German Low-Grade Lymphoma Study Group. J Clin Oncol. 1998 May;16(5):1922-30. [https://doi.org/10.1200/JCO.1998.16.5.1922 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9586911 PubMed]
 
−
# Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, Solal-Celigny P, Offner F, Walewski J, Raposo J, Jack A, Smith P. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005 Feb 15;105(4):1417-23. Epub 2004 Oct 19.[http://www.bloodjournal.org/content/105/4/1417.full link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15494430 PubMed]
 
−
## '''Update:''' Marcus R, Imrie K, Solal-Celigny P, Catalano JV, Dmoszynska A, Raposo JC, Offner FC, Gomez-Codina J, Belch A, Cunningham D, Wassner-Fritsch E, Stein G. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008 Oct 1;26(28):4579-86. Epub 2008 Jul 28. [https://doi.org/10.1200/jco.2007.13.5376 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18662969 PubMed]
 
−
# Hagenbeek A, Eghbali H, Monfardini S, Vitolo U, Hoskin PJ, de Wolf-Peeters C, MacLennan K, Staab-Renner E, Kalmus J, Schott A, Teodorovic I, Negrouk A, van Glabbeke M, Marcus R. Phase III intergroup study of fludarabine phosphate compared with cyclophosphamide, vincristine, and prednisone chemotherapy in newly diagnosed patients with stage III and IV low-grade malignant Non-Hodgkin's lymphoma. J Clin Oncol. 2006 Apr 1;24(10):1590-6. [https://doi.org/10.1200/JCO.2005.03.7952 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16575010 PubMed]
 
−
<!-- Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL, and the Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL. -->
 
−
# '''ECOG E1496:''' Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. [https://doi.org/10.1200/jco.2008.17.1561 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668968/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19255334 PubMed] NCT00003204
 
−
## '''Update:''' Barta SK, Li H, Hochster HS, Hong F, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Colocci N, Bengtson EM, Horning SJ, Kahl BS. Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496). Cancer. 2016 Oct;122(19):2996-3004. Epub 2016 Jun 28. [https://doi.org/10.1002/cncr.30137 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030179/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27351685 PubMed]
 
−
==CVP, then <sup>131</sup>Iodine-Tositumomab {{#subobject:60e420|Regimen=1}}==
 
−
CVP-RIT: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone, then '''<u>R</u>'''adio'''<u>I</u>'''mmuno'''<u>T</u>'''herapy
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:1e9d16|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2009.27.8325 Link et al. 2010]
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, CVP portion====
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy, CVP portion====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for 6 cycles, followed within 56 days by:'''
 
−
====Radioconjugate therapy, dosimetric step====
 
−
*On Day 1, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with 5 mCi of Iodine-131]] IV over 20 minutes
 
−
**First scan of whole body dosimetry & redistribution within 1 hour of finishing dosimetric dose on day 1
 
−
*Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
 
−
*Day 6 or 7: Third scan of whole body dosimetry & redistribution
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO three times per day, Lugol solution 20 drops PO three times per day, or potassium iodide tablets 130 mg PO once per day, starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion
 
−
====Radioconjugate therapy, therapeutic step====
 
−
*Any one day 7 to 14 days after dosimetric infusion, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour, given first
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body]] IV over 20 minutes
 
−
***65 cGy total body dose used for patients with platelet counts of 100 to 150,000/mm3
 
−
''Calculated dose of I-131 is based on information from serial total-body gamma-camera counts''
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO three times per day, Lugol solution 20 drops PO three times per day, or potassium iodide tablets 130 mg PO once per day, starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion
 
−
</div></div>
 
−
===References===
 
−
# Link BK, Martin P, Kaminski MS, Goldsmith SJ, Coleman M, Leonard JP. Cyclophosphamide, vincristine, and prednisone followed by tositumomab and iodine-131-tositumomab in patients with untreated low-grade follicular lymphoma: eight-year follow-up of a multicenter phase II study. J Clin Oncol. 2010 Jun 20;28(18):3035-41. Epub 2010 May 10. [https://doi.org/10.1200/jco.2009.27.8325 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20458031 PubMed].
 
−
==Fludarabine monotherapy {{#subobject:227afa|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:0332ee|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://doi.org/10.1200/JCO.2000.18.4.773 Zinzani et al. 2000]
 
−
|1995-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fludarabine_.26_Idarubicin_99|Fludarabine & Idarubicin]]
 
−
| style="background-color:#1a9850" |Superior CR rate<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>The superiority of this arm was only observed in the FL subgroup; overall, there was no statistically significant difference between arms.''<br>
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]]
 
−
</div></div>
 
−
===References===
 
−
# Zinzani PL, Magagnoli M, Moretti L, De Renzo A, Battista R, Zaccaria A, Guardigni L, Mazza P, Marra R, Ronconi F, Lauta VM, Bendandi M, Gherlinzoni F, Gentilini P, Ciccone F, Cellini C, Stefoni V, Ricciuti F, Gobbi M, Tura S. Randomized trial of fludarabine versus fludarabine and idarubicin as frontline treatment in patients with indolent or mantle-cell lymphoma. J Clin Oncol. 2000 Feb;18(4):773-9. [https://doi.org/10.1200/JCO.2000.18.4.773 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10673518 PubMed]
 
−
==FC {{#subobject:9f1357|Regimen=1}}==
 
−
FC: '''<u>F</u>'''ludarabine & '''<u>C</u>'''yclophosphamide
 
−
<br>CF: '''<u>C</u>'''yclophosphamide & '''<u>F</u>'''ludarabine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5b37b5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/PMC2668968/ Hochster et al. 2009 (ECOG E1496)]
 
−
|NR
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#CVP|CVP]]
 
−
|style="background-color:#d3d3d3"|Not reported
 
−
|-
 
−
|}
 
−
''Note: investigation into this regimen was halted due to excess mortality.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
 
−
'''28-day cycle up to 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Follicular_lymphoma#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance versus [[Follicular_lymphoma#Observation_2|observation]]
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL, and the Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL. -->
 
−
# '''ECOG E1496:''' Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. [https://doi.org/10.1200/jco.2008.17.1561 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19255334 PubMed]
 
−
==Fludarabine, then <sup>131</sup>Iodine-Tositumomab {{#subobject:d9d902|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:0e2b27|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.14.803 Leonard et al. 2005]
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
'''35-day cycle for 3 cycles, followed by:'''
 
−
====Radioconjugate therapy, dosimetric step====
 
−
*On Day 0, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with 5 mCi of Iodine-131]] IV over 20 minutes
 
−
**First scan of whole body dosimetry & redistribution
 
−
*Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
 
−
*Day 6 or 7: Third scan of whole body dosimetry & redistribution
 
−
====Radioconjugate therapy, therapeutic step====
 
−
*Any day from day 7 to 14, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body]] IV over 20 minutes
 
−
***65 cGy total body dose used for patients with platelet counts of 100 to 150,000/mm3
 
−
''Calculated dose of I-131 is based on information from serial total-body gamma-camera counts''
 
−
</div></div>
 
−
===References===
 
−
# Leonard JP, Coleman M, Kostakoglu L, Chadburn A, Cesarman E, Furman RR, Schuster MW, Niesvizky R, Muss D, Fiore J, Kroll S, Tidmarsh G, Vallabhajosula S, Goldsmith SJ. Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma. J Clin Oncol. 2005 Aug 20;23(24):5696-704. [https://doi.org/10.1200/jco.2005.14.803 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16110029 PubMed]
 
−
==FM {{#subobject:6a2469|Regimen=1}}==
 
−
FM: '''<u>F</u>'''ludarabine, '''<u>M</u>'''itoxantrone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 75/10, IV fludarabine {{#subobject:ee1449|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://doi.org/10.1200/jco.2004.07.170 Zinzani et al. 2004]
 
−
|1999-2002
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#CHOP|CHOP]]
 
−
| style="background-color:#1a9850" |Superior CR rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with PR or CR with detectable bcl-2/IgH fusion by PCR: [[Follicular_lymphoma#Rituximab_monotherapy.2C_abbreviated_course|R]] x 4
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 100/10, IV fludarabine {{#subobject:6b877b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://doi.org/10.1093/annonc/mdi091 Foussard et al. 2005]
 
−
|1995-1999
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#mini-CHVP_88|mini-CHVP]]
 
−
| style="background-color:#1a9850" |Superior FFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 1
 
−
'''28-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#FM_88|FM]] consolidation
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 120/10, PO fludarabine {{#subobject:be3ef5|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(08)70039-1 Zinzani et al. 2008 (FLUMIZ)]
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#f7fcfd" |ORR: 98%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 3
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Allopurinol (Zyloprim)]] 300 mg PO once per day for patients with bulky disease
 
−
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] by the following criteria:
 
−
**Prophylaxis: None
 
−
**Grade 3 or 4 neutropenia or delayed neutropenic fever: could be given growth factors for later cycles at physician discretion
 
−
'''28-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients were restaged 4 to 6 weeks after finishing cycle 6. People with at least a partial response (PR), ANC greater than 1500/uL, platelet count greater than 100 x 10<sup>9</sup>/L, and less than 25% bone marrow involvement were eligible for [[Follicular_lymphoma#Ibritumomab_tiuxetan_protocol_2|consolidation therapy with ibritumomab tiuxetan]] 6 to 10 weeks after the end of cycle 6.
 
−
</div></div>
 
−
===References===
 
−
# Zinzani PL, Pulsoni A, Perrotti A, Soverini S, Zaja F, De Renzo A, Storti S, Lauta VM, Guardigni L, Gentilini P, Tucci A, Molinari AL, Gobbi M, Falini B, Fattori PP, Ciccone F, Alinari L, Martelli M, Pileri S, Tura S, Baccarani M. Fludarabine plus mitoxantrone with and without rituximab versus CHOP with and without rituximab as front-line treatment for patients with follicular lymphoma. J Clin Oncol. 2004 Jul 1;22(13):2654-61. Epub 2004 May 24. [https://doi.org/10.1200/jco.2004.07.170 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15159414 PubMed]
 
−
# Foussard C, Colombat P, Maisonneuve H, Berthou C, Gressin R, Rousselet MC, Rachieru P, Pignon B, Mahé B, Ghandour C, Desablens B, Casassus P, Lamy T, Delwail V, Deconinck E; GOELAMS. Long-term follow-up of a randomized trial of fludarabine-mitoxantrone, compared with cyclophosphamide, doxorubicin, vindesine, prednisone (CHVP), as first-line treatment of elderly patients with advanced, low-grade non-Hodgkin's lymphoma before the era of monoclonal antibodies. Ann Oncol. 2005 Mar;16(3):466-72. Epub 2005 Feb 2. [https://doi.org/10.1093/annonc/mdi091 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15695500 PubMed]
 
−
# '''FLUMIZ:''' Zinzani PL, Tani M, Pulsoni A, Gobbi M, Perotti A, De Luca S, Fabbri A, Zaccaria A, Voso MT, Fattori P, Guardigni L, Ronconi S, Cabras MG, Rigacci L, De Renzo A, Marchi E, Stefoni V, Fina M, Pellegrini C, Musuraca G, Derenzini E, Pileri S, Fanti S, Piccaluga PP, Baccarani M. Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ). Lancet Oncol. 2008 Apr;9(4):352-8. Epub 2008 Mar 14. [https://doi.org/10.1016/S1470-2045(08)70039-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18342572 PubMed] EudraCT 2004-002211-92
 
−
==FND {{#subobject:6b3e61|Regimen=1}}==
 
−
FND: '''<u>F</u>'''ludarabine, '''<u>N</u>'''ovantrone (Mitoxantrone), '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b32c08|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1996.14.4.1262 McLaughlin et al. 1996]
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg/day IV or PO on days 1 to 5
 
−
'''28-day cycle for up to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# McLaughlin P, Hagemeister FB, Romaguera JE, Sarris AH, Pate O, Younes A, Swan F, Keating M, Cabanillas F. Fludarabine, mitoxantrone, and dexamethasone: an effective new regimen for indolent lymphoma. J Clin Oncol. 1996 Apr;14(4):1262-8. [https://doi.org/10.1200/jco.1996.14.4.1262 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8648382 PubMed]
 
−
==<sup>131</sup>Iodine-Tositumomab monotherapy {{#subobject:f69726|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:a80cf3|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa041511 Kaminski et al. 2005]
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radioconjugate therapy, dosimetric step====
 
−
*On Day 0, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with 5 mCi of Iodine-131]] IV over 20 minutes
 
−
**First scan of whole body dosimetry & redistribution
 
−
*Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
 
−
*Day 6 or 7: Third scan of whole body dosimetry & redistribution
 
−
====Radioconjugate therapy, therapeutic step====
 
−
*Any day from day 7 to 14, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body]] IV over 20 minutes
 
−
***65 cGy total body dose used for patients with platelet counts of 100 to 150,000/mm3
 
−
''Calculated dose of I-131 is based on information from serial total-body gamma-camera counts''
 
−
</div></div>
 
−
===References===
 
−
# Kaminski MS, Tuck M, Estes J, Kolstad A, Ross CW, Zasadny K, Regan D, Kison P, Fisher S, Kroll S, Wahl RL. 131I-tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med. 2005 Feb 3;352(5):441-9. [https://doi.org/10.1056/NEJMoa041511 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15689582 PubMed]
 
−
## '''Update: Abstract:''' Mark S. Kaminski, MD, Melissa Tuck, MS, Judith Estes, BSN, MSN, Arne Kolstad, MD, PhD, Charles Warren Ross, MD, Denise Regan, BS, Thierry Horner, PhD, Vanessa C. Williams, MS, Tina Vleisides, DC and Richard L. Wahl, MD. Tositumomab and Iodine I-131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma:  Median 10 Year Follow-up Results. ASH 2009 abstract 3759.
 
−
==MCP {{#subobject:5510fa|Regimen=1}}==
 
−
MCP: '''<u>M</u>'''itoxantrone, '''<u>C</u>'''hlorambucil, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a8501b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://doi.org/10.1002/cncr.22093 Nickenig et al. 2006 (GLSG '96)]
 
−
|1996-1998
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#CHOP|CHOP]]
 
−
|style="background-color:#fee08b"|Might have inferior CR rate
 
−
|-
 
−
|}
 
−
''Note: the chlorambucil dose is written in the reference as "3 x 3 mg/m<sup>2</sup>"; total dose per day is 9 mg/m<sup>2</sup>.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
*[[Chlorambucil (Leukeran)]] 3 mg/m<sup>2</sup> PO three times per day on days 1 to 5
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 25 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''28-day cycle for 6 to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''GLSG '96:''' Nickenig C, Dreyling M, Hoster E, Pfreundschuh M, Trumper L, Reiser M, Wandt H, Lengfelder E, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. Combined cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) improves response rates but not survival and has lower hematologic toxicity compared with combined mitoxantrone, chlorambucil, and prednisone (MCP) in follicular and mantle cell lymphomas: results of a prospective randomized trial of the German Low-Grade Lymphoma Study Group. Cancer. 2006 Sep 1;107(5):1014-22. [https://doi.org/10.1002/cncr.22093 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16878325 PubMed]
 
−
==MCP (Prednisolone) {{#subobject:5762fa|Regimen=1}}==
 
−
MCP: '''<u>M</u>'''itoxantrone, '''<u>C</u>'''hlorambucil, '''<u>P</u>'''rednisolone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:75c24e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://doi.org/10.1200/jco.2006.06.4618 Herold et al. 2007 (OSHO-39)]
 
−
|1998-2003
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Follicular_lymphoma#R-MCP|R-MCP]]
 
−
|style="background-color:#d73027"|Inferior OS
 
−
|-
 
−
|}
 
−
''Note: the chlorambucil dose is written in the reference as "3 x 3 mg/m<sup>2</sup>"; total dose per day is 9 mg/m<sup>2</sup>.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
*[[Chlorambucil (Leukeran)]] 3 mg/m<sup>2</sup> PO three times per day on days 1 to 5
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 25 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''28-day cycle for up to 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients who achieved a PR or CR: [[#Interferon_alfa-2a_monotherapy|Interferon alfa-2a]] maintenance, within 4 to 8 weeks of completion of chemotherapy
 
−
</div></div>
 
−
===References===
 
−
# '''OSHO-39:''' Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, Dölken G, Naumann R, Knauf W, Freund M, Rohrberg R, Höffken K, Franke A, Ittel T, Kettner E, Haak U, Mey U, Klinkenstein C, Assmann M, von Grünhagen U; East German Study Group Hematology and Oncology Study. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007 May 20;25(15):1986-92. Epub 2007 Apr 9. [https://doi.org/10.1200/jco.2006.06.4618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17420513 PubMed] NCT00269113
 
−
## '''Update:''' Herold M, Scholz CW, Rothmann F, Hirt C, Lakner V, Naumann R. Long-term follow-up of rituximab plus first-line mitoxantrone, chlorambucil, prednisolone and interferon-alpha as maintenance therapy in follicular lymphoma. J Cancer Res Clin Oncol. 2015 Sep;141(9):1689-95. Epub 2015 Mar 25. [http://link.springer.com/article/10.1007/s00432-015-1963-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25804839 PubMed]
 
−
==ProMACE-MOPP {{#subobject:0aa31b|Regimen=1}}==
 
−
ProMACE-MOPP: '''<u>Pro</u>'''lix (Prednisone), '''<u>M</u>'''ethotrexate, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>M</u>'''ustargen (Mechlorethamine), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:cf90b9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 33%"|Comparator
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/2456618 Young et al. 1988]
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[Follicular_lymphoma#Observation|Observation]]
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Etoposide (Vepesid)]]
 
−
*[[Mechlorethamine (Mustargen)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Procarbazine (Matulane)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)|Prednisone (Prolix)]]
 
−
*[[Prednisone (Sterapred)]]
 
−
</div></div>
 
−
===References===
 
−
# Young RC, Longo DL, Glatstein E, Ihde DC, Jaffe ES, DeVita VT Jr. The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. Semin Hematol. 1988 Apr;25(2 Suppl 2):11-6. [https://pubmed.ncbi.nlm.nih.gov/2456618 PubMed]
 
−
=Consolidation after first-line therapy=
 
−
==<sup>131</sup>Iodine-Tositumomab monotherapy {{#subobject:1d80fc|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9cd058|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107050/ Friedberg et al. 2014 (SWOG S0433)]
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
Will be added if drug is ever returned to market.
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Follicular_lymphoma#R-CHOP|R-CHOP]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radioconjugate therapy====
 
−
*[[Tositumomab and I-131 (Bexxar)]]
 
−
</div></div>
 
−
===References===
 
−
# '''SWOG S0433:''' Friedberg JW, Unger JM, Burack WR, Gopal AK, Raju RN, Nademanee AP, Kaminski MS, Li H, Press OW, Miller TP, Fisher RI. R-CHOP with iodine-131 tositumomab consolidation for advanced stage diffuse large B-cell lymphoma (DLBCL): SWOG S0433. Br J Haematol. 2014 Aug;166(3):382-9. Epub 2014 Apr 18. [https://doi.org/10.1111/bjh.12906 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107050/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24749780 PubMed] NCT00107380
 
−
=Maintenance after first-line therapy=
 
−
==Interferon alfa-2a monotherapy {{#subobject:d62b86|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 3 MU TIW {{#subobject:0a71d7|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/112/13/4824.full Salles et al. 2008 (FL2000)]
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''This variant was intended for patients older than 70 years.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Follicular_lymphoma#R-CHVP.2BI|R-CHVP+I]] versus [[#CHVP-I|CHVP+I]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Interferon alfa-2a (Roferon-A)]] 3,000,000 units SC once per day on days 1, 3, 5 (three times per week)
 
−
'''7-day cycle for 78 cycles (18 months)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 4.5 MU TIW x 18 mo {{#subobject:0b61d7|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/112/13/4824.full Salles et al. 2008 (FL2000)]
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''This variant was intended for patients younger than 70 years.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Follicular_lymphoma#R-CHVP.2BI|R-CHVP+I]] versus [[#CHVP-I|CHVP+I]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Interferon alfa-2a (Roferon-A)]] 4,500,000 units SC once per day on days 1, 3, 5 (three times per week)
 
−
'''7-day cycle for 78 cycles (18 months)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 4.5 MU TIW, indefinitely {{#subobject:79c7d4|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.06.4618 Herold et al. 2007 (OSHO-39)]
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#MCP_.28Prednisolone.29|MCP]] versus [[Follicular_lymphoma#R-MCP|R-MCP]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Interferon alfa-2a (Roferon-A)]] 4,500,000 units (route not specified) once per day on days 1, 3, 5 (three times per week)
 
−
'''7-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 5 MU TIW {{#subobject:79c0a4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/104/9/2667.long Lenz et al. 2004]
 
−
|1996-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_TBI.2C_then_auto_HSCT_88|Cy/TBI, then auto HSCT]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#CHOP|CHOP]] or [[#MCP|MCP]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Interferon alfa-2a (Roferon-A)]] 5,000,000 units SC once per day on days 1, 3, 5 (three times per week)
 
−
'''7-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Lenz G, Dreyling M, Schiegnitz E, Forstpointner R, Wandt H, Freund M, Hess G, Truemper L, Diehl V, Kropff M, Kneba M, Schmitz N, Metzner B, Pfirrmann M, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma: results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 1;104(9):2667-74. Epub 2004 Jul 6. [http://www.bloodjournal.org/content/104/9/2667.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15238420 PubMed]
 
−
# '''OSHO-39:''' Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, Dölken G, Naumann R, Knauf W, Freund M, Rohrberg R, Höffken K, Franke A, Ittel T, Kettner E, Haak U, Mey U, Klinkenstein C, Assmann M, von Grünhagen U; East German Study Group Hematology and Oncology Study. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007 May 20;25(15):1986-92. Epub 2007 Apr 9. [https://doi.org/10.1200/jco.2006.06.4618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17420513 PubMed] NCT00269113
 
−
# '''FL2000:''' Salles G, Mounier N, de Guibert S, Morschhauser F, Doyen C, Rossi JF, Haioun C, Brice P, Mahé B, Bouabdallah R, Audhuy B, Ferme C, Dartigeas C, Feugier P, Sebban C, Xerri L, Foussard C. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 2008 Dec 15;112(13):4824-31. Epub 2008 Sep 17. [http://www.bloodjournal.org/content/112/13/4824.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18799723 PubMed] NCT00136552
 
−
## '''Update:''' Bachy E, Houot R, Morschhauser F, Sonet A, Brice P, Belhadj K, Cartron G, Audhuy B, Fermé C, Feugier P, Sebban C, Delwail V, Maisonneuve H, Le Gouill S, Lefort S, Brousse N, Foussard C, Salles G; Groupe d'Etude des Lymphomes de l'Adulte (GELA). Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma. Haematologica. 2013 Jul;98(7):1107-14. Epub 2013 May 3. [http://www.haematologica.org/content/98/7/1107.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696615/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23645690 PubMed]
 
−
=Relapsed or refractory=
 
−
==CHOP {{#subobject:3a1597|Regimen=1}}==
 
−
CHOP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9d2627|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/108/10/3295.long Van Oers et al. 2006 (EORTC 20981)]
 
−
|1998-2004
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Follicular_lymphoma#R-CHOP_2|R-CHOP]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) 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 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders (PR or CR): [[Follicular_lymphoma#Rituximab_monotherapy.2C_extended_course_2|Rituximab]] maintenance versus [[Follicular_lymphoma#Observation_3|no further treatment]]
 
−
</div></div>
 
−
===References===
 
−
# '''EORTC 20981:''' van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van 't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. [http://www.bloodjournal.org/content/108/10/3295.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16873669 PubMed] NCT00004179
 
−
##'''Update:''' van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.26.5827 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20439641 PubMed]
 
−
==FCM {{#subobject:294f6d|Regimen=1}}==
 
−
FCM: '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''itoxantrone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f3f288|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/104/10/3064.long Forstpointner et al. 2004]
 
−
|1998-2001
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Follicular_lymphoma#R-FCM_2|R-FCM]]
 
−
|style="background-color:#fc8d59"|Seems to have inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3
 
−
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3
 
−
*[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 
−
'''28-day cycle for 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders (PR or CR): [[Follicular_lymphoma#Rituximab_monotherapy.2C_abbreviated_course_2|Rituximab]] maintenance versus [[Follicular_lymphoma#Observation_3|no further treatment]]
 
−
</div></div>
 
−
===References===
 
−
# Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. [http://www.bloodjournal.org/content/104/10/3064.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15284112 PubMed]
 
−
## '''Update:''' Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. [http://www.bloodjournal.org/content/108/13/4003.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16946304 PubMed]
 
−
==Fludarabine monotherapy {{#subobject:f8gyaa|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5798ue|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://doi.org/10.1200/JCO.2002.11.068 Klasa et al. 2002]
 
−
|1993-1996
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#CVP_88|CVP]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Klasa RJ, Meyer RM, Shustik C, Sawka CA, Smith A, Guévin R, Maksymiuk A, Rubinger M, Samosh M, Laplante S, Grenier JF. Randomized phase III study of fludarabine phosphate versus cyclophosphamide, vincristine, and prednisone in patients with recurrent low-grade non-Hodgkin's lymphoma previously treated with an alkylating agent or alkylator-containing regimen. J Clin Oncol. 2002 Dec 15;20(24):4649-54. [https://doi.org/10.1200/JCO.2002.11.068 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488409 PubMed]
 
−
==FMP {{#subobject:f1669a|Regimen=1}}==
 
−
FMP: '''<u>F</u>'''ludarabine, '''<u>M</u>'''itoxantrone, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:57301e|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/j.1600-0609.1995.tb00269.x Zinzani et al. 1995a]
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]]
 
−
*[[Mitoxantrone (Novantrone)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]]
 
−
</div></div>
 
−
===References===
 
−
# Zinzani PL, Bendandi M, Tura S. FMP regimen (fludarabine, mitoxantrone, prednisone) as therapy in recurrent low-grade non-Hodgkin's lymphoma. Eur J Haematol. 1995 Oct;55(4):262-6. [https://doi.org/10.1111/j.1600-0609.1995.tb00269.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/7589345 PubMed]
 
−
==Fludarabine & Rituximab (FR) {{#subobject:c96961|Regimen=1}}==
 
−
FR: '''<u>F</u>'''ludarabine & '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5ba252|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://doi.org/10.1016/S1470-2045(15)00447-7 Rummel et al. 2015 (StiL NHL 2-2003)]
 
−
|2003-2010
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Follicular_lymphoma#Bendamustine_.26_Rituximab_.28BR.29_2|BR]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> (route not specified) once per day on days 1 to 3
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Mathias J. Rummel, MD, PhD, Ulrich Kaiser, MD, Christina Balser, Martina Beate Stauch, Wolfram Brugger, MD, PhD, Manfred Welslau, Norbert Niederle, Christoph Losem, Harald Ballo, Eckhart Weidmann, Ulrich von Gruenhagen, Lothar Mueller, Michael Sandherr, MD, Julia Vereschagina, Axel Hinke and Juergen Barth. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab In Patients with Relapsed Follicular, Indolent and Mantle Cell Lymphomas – Final Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany). ASH Annual Meeting 2010, Abstract 856 [https://ash.confex.com/ash/2010/webprogram/Paper26917.html link to abstract]
 
−
## '''Update:''' '''Abstract:''' Mathias J. Rummel, MD, Christina Balser, MD, Ulrich Kaiser, MD, Hans Peter Böck, Martina Beate Stauch, MD, Andrea Heider, PhD, Manfred Welslau, Christoph Losem, Eckhart Weidmann, Wolfgang Blau, MD, Alexander Burchardt, MD, Jürgen Barth, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab in Patients with Relapsed Follicular, Indolent, or Mantle Cell Lymphomas – 8-Year Follow-up Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany). ASH Annual Meeting 2014, Abstract 145 [https://ash.confex.com/ash/2014/webprogram/Paper69154.html link to abstract] -->
 
−
# '''StiL NHL 2-2003:''' Rummel M, Kaiser U, Balser C, Stauch M, Brugger W, Welslau M, Niederle N, Losem C, Boeck HP, Weidmann E, von Gruenhagen U, Mueller L, Sandherr M, Hahn L, Vereshchagina J, Kauff F, Blau W, Hinke A, Barth J; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial. Lancet Oncol. 2016 Jan;17(1):57-66. Epub 2015 Dec 5. [https://doi.org/10.1016/S1470-2045(15)00447-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26655425 PubMed] NCT01456351
 
−
==Idelalisib monotherapy {{#subobject:7fef70|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:cea36|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039496/ Gopal et al. 2014 (DELTA)]
 
−
|2011-2012
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Idelalisib (Zydelig)]] 150 mg PO twice per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
#'''DELTA:''' Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kd inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014 Mar 13;370(11):1008-18. Epub 2014 Jan 22. [https://doi.org/10.1056/NEJMoa1314583 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039496/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24450858 PubMed] NCT01282424
 
−
##'''Update:''' '''Abstract:''' Ajay K. Gopal, MD, Brad S. Kahl, MD, Sven de Vos, MD, PhD, Nina D. Wagner-Johnston, MD, Stephen J. Schuster, MD, Wojciech Jurczak, MD, PhD, Ian W. Flinn, MD, PhD, Christopher R. Flowers, MD, Peter Martin, MD, Andreas Viardot, MD, Kristie A. Blum, MD, Andre Goy, MD, Andrew Davies, BM PhD, Pier Luigi Zinzani, MD, Martin H. Dreyling, MD, PhD, Leanne M. Holes, Bess Sorensen, PhD, Wayne R. Godfrey, MD and Gilles Andre Salles, MD, PhD. Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL). Blood 2014 124:1708. [http://www.bloodjournal.org/content/124/21/1708 link to abstract]
 
−
==Interferon alfa monotherapy {{#subobject:10dcf2|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:042fbd|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198411013111803 Foon et al. 1984]
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[:Category:Interferons|Interferon alfa]]
 
−
</div></div>
 
−
===References===
 
−
# Foon KA, Sherwin SA, Abrams PG, Longo DL, Fer MF, Stevenson HC, Ochs JJ, Bottino GC, Schoenberger CS, Zeffren J, Jaffe ES, Oldham RK. Treatment of advanced non-Hodgkin's lymphoma with recombinant leukocyte A interferon. N Engl J Med. 1984 Nov 1;311(18):1148-52. [https://doi.org/10.1056/NEJM198411013111803 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6482933 PubMed]
 
−
==<sup>131</sup>Iodine-Tositumomab monotherapy {{#subobject:e69735|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3515b6|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199308123290703 Kaminski et al. 1993]
 
−
|NR
 
−
| style="background-color:#ffffbe" |Non-randomized, <20 pts
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(95)92225-3 Press et al. 1995]
 
−
|NR
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2001.19.19.3918 Kaminski et al. 2001 (RIT-II-004)]
 
−
|1996-1998
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.07.040 Horning et al. 2004 (CP-97-012)]
 
−
|1998-1999
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
|-
 
−
|[https://doi.org/10.3109/10428194.2014.894190 Olney et al. 2014 (SB-393229/032)]
 
−
|2004-2007
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
''Note: Kiminski et al. 1993 and Press et al. 1995 are included here for historic context but had different treatment details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radioconjugate therapy, dosimetric step====
 
−
*On Day 0, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with 5 mCi of Iodine-131]] IV over 20 minutes
 
−
**First scan of whole body dosimetry & redistribution
 
−
*Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
 
−
*Day 6 or 7: Third scan of whole body dosimetry & redistribution
 
−
====Radioconjugate therapy, therapeutic step====
 
−
*Any day from day 7 to 15, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body]] IV over 20 minutes
 
−
***65 cGy total body dose used for patients with platelet counts of 100 to 150,000/mm3
 
−
''Calculated dose of I-131 is based on information from serial total-body gamma-camera counts''
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*Potassium iodide  (SSKI, saturated solution of potassium iodide) 2 drops PO three times per day starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion; may also use Lugol’s solution or potassium iodide tablets
 
−
</div></div>
 
−
===References===
 
−
# Kaminski MS, Zasadny KR, Francis IR, Milik AW, Ross CW, Moon SD, Crawford SM, Burgess JM, Petry NA, Butchko GM, Glenn SD, Wahl RL. Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody. N Engl J Med. 1993 Aug 12;329(7):459-65. [https://doi.org/10.1056/NEJM199308123290703 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7687326 PubMed]
 
−
# Press OW, Eary JF, Appelbaum FR, Martin PJ, Nelp WB, Glenn S, Fisher DR, Porter B, Matthews DC, Gooley T, Bernstein ID. Phase II trial of 131I-B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas. Lancet. 1995 Aug 5;346(8971):336-40. [https://doi.org/10.1016/s0140-6736(95)92225-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7623531 PubMed]
 
−
# '''RIT-II-004:''' Kaminski MS, Zelenetz AD, Press OW, Saleh M, Leonard J, Fehrenbacher L, Lister TA, Stagg RJ, Tidmarsh GF, Kroll S, Wahl RL, Knox SJ, Vose JM. Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2001 Oct 1;19(19):3918-28. [https://doi.org/10.1200/jco.2001.19.19.3918 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11579112 PubMed]
 
−
# '''CP-97-012:''' Horning SJ, Younes A, Jain V, Kroll S, Lucas J, Podoloff D, Goris M. Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J Clin Oncol. 2005 Feb 1;23(4):712-9. Epub 2004 Dec 21. [https://doi.org/10.1200/JCO.2005.07.040 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15613695 PubMed]
 
−
# '''Meta-analysis:''' Fisher RI, Kaminski MS, Wahl RL, Knox SJ, Zelenetz AD, Vose JM, Leonard JP, Kroll S, Goldsmith SJ, Coleman M. Tositumomab and iodine-131 tositumomab produces durable complete remissions in a subset of heavily pretreated patients with low-grade and transformed non-Hodgkin's lymphomas. J Clin Oncol. 2005 Oct 20;23(30):7565-73. Epub 2005 Sep 26. [https://doi.org/10.1200/jco.2004.00.9217 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16186600 PubMed]
 
−
# '''SB-393229/032:''' Olney HJ, Freeman MA, Stewart DA, Mangel JE, White DJ, Elia-Pacitti JO. Prolonged progression-free survival and preserved quality of life in the Canadian prospective study of tositumomab and iodine(131)-tositumomab for previously treated, rituximab-exposed, indolent non-Hodgkin lymphoma. Leuk Lymphoma. 2014 Dec;55(12):2754-60. Epub 2014 Apr 3. [https://doi.org/10.3109/10428194.2014.894190 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24528219 PubMed] NCT00240565
 
−
==Ofatumumab monotherapy {{#subobject:a875bf|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ddfe7d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/111/12/5486.long Hagenbeek et al. 2008 (Hx-CD20-001)]
 
−
|2004-2005
 
−
| style="background-color:#91cf61" |Phase 1/2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/119/16/3698.long Czucman et al. 2012 (405 Study)]
 
−
|2006-2008
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7448588/ Maloney et al. 2020 (HOMER)]
 
−
|2010-2016
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Follicular_lymphoma#Rituximab_monotherapy_3|Rituximab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
''Note: there was no MTD determined in Hx-CD20-001.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ofatumumab (Arzerra)]] as follows:
 
−
**Cycle 1: 300 mg IV once on day 1, then 1000 mg IV once per day on days 8, 15, 22
 
−
**Cycle 2: 1000 mg IV once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 1000 mg (no route specified) before each dose of [[Ofatumumab (Arzerra)]]
 
−
*[[Cetirizine (Zyrtec)]] 10 mg (or equivalent) PO before each dose of [[Ofatumumab (Arzerra)]]
 
−
*[[Prednisolone (Millipred)]] (or equivalent) 100 mg before dose 1 and 2 of [[Ofatumumab (Arzerra)]]
 
−
'''28-day cycle for 2 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''Hx-CD20-001:''' Hagenbeek A, Gadeberg O, Johnson P, Pedersen LM, Walewski J, Hellmann A, Link BK, Robak T, Wojtukiewicz M, Pfreundschuh M, Kneba M, Engert A, Sonneveld P, Flensburg M, Petersen J, Losic N, Radford J. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood. 2008 Jun 15;111(12):5486-95. Epub 2008 Apr 4. [http://www.bloodjournal.org/content/111/12/5486.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/18390837 PubMed] NCT00092274
 
−
#'''405 Study:''' Czuczman MS, Fayad L, Delwail V, Cartron G, Jacobsen E, Kuliczkowski K, Link BK, Pinter-Brown L, Radford J, Hellmann A, Gallop-Evans E, DiRienzo CG, Goldstein N, Gupta I, Jewell RC, Lin TS, Lisby S, Schultz M, Russell CA, Hagenbeek A; 405 Study Investigators. Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study. Blood. 2012 Apr 19;119(16):3698-704. Epub 2012 Mar 2. [http://www.bloodjournal.org/content/119/16/3698.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22389254 PubMed] NCT00394836
 
−
#'''HOMER:''' Maloney DG, Ogura M, Fukuhara N, Davis J, Lasher J, Izquierdo M, Banerjee H, Tobinai K. A phase 3 randomized study (HOMER) of ofatumumab vs rituximab in iNHL relapsed after rituximab-containing therapy. Blood Adv. 2020 Aug 25;4(16):3886-3893. [https://doi.org/10.1182/bloodadvances.2020001942 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7448588/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32810220 PubMed] NCT01200589
 
−
==Umbralisib monotherapy {{#subobject:98gja1|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1y82ef|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8148421/ Fowler et al. 2021 (UNITY-NHL)]
 
−
|2017-2018
 
−
| style="background-color:#91cf61" |Phase 2b (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Umbralisib (Ukoniq)]] 800 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
<!-- #'''Abstract:''' Nathan Hale Fowler, Felipe Samaniego, Wojciech Jurczak, Ewa Lech-Maranda, Nilanjan Ghosh, Piers Patten, James Andrew Reeves, Lori Ann Leslie, Julio C. Chavez, Paolo Ghia, Corrado Tarella, John M. Burke, Jeff Porter Sharman, Kathryn Kolibaba, Owen A. O'Connor, Chan Cheah, Hari P. Miskin, Peter Sportelli, Michael S. Weiss, and Pier Luigi Zinzani. Umbralisib monotherapy demonstrates efficacy and safety in patients with relapsed/refractory marginal zone lymphoma: A multicenter, open label, registration directed phase II study. Journal of Clinical Oncology 2019 37:15_suppl, 7506-7506 [https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.7506 link to abstract] -->
 
−
#'''UNITY-NHL:''' Fowler NH, Samaniego F, Jurczak W, Ghosh N, Derenzini E, Reeves JA, Knopińska-Posłuszny W, Cheah CY, Phillips T, Lech-Maranda E, Cheson BD, Caimi PF, Grosicki S, Leslie LA, Chavez JC, Fonseca G, Babu S, Hodson DJ, Shao SH, Burke JM, Sharman JP, Law JY, Pagel JM, Miskin HP, Sportelli P, O'Connor OA, Weiss MS, Zinzani PL. Umbralisib, a Dual PI3Kδ/CK1ε Inhibitor in Patients With Relapsed or Refractory Indolent Lymphoma. J Clin Oncol. 2021 May 20;39(15):1609-1618. Epub 2021 Mar 8. [https://doi.org/10.1200/jco.20.03433 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8148421/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33683917/ PubMed] NCT02793583
 
−
[[Category:Follicular lymphoma regimens]]
 
−
[[Category:Historical regimens]]
 
−
[[Category:Disease-specific pages]]
 
−
[[Category:Indolent lymphomas]]
 
−
[[Category:Non-Hodgkin lymphomas]]
 

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