Follicular lymphoma - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? Please go to the main follicular lymphoma regimen page to find other regimens.
Last updated on 2024-12-02:18 regimens on this page
24 variants on this page
 
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==
CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
===Regimen variant #1, capped vincristine===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Nickenig et al. 2006 (GLSG '96) 	1996-1998 	Phase 3 (E-switch-ic)	MCP 	Might have higher CR rate
Hiddemann et al. 2005 (GLSG '00)	2000-2003 	Phase 3 (C) 	R-CHOP 	Shorter OS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
21-day cycle for 6 to 8 cycles
===Regimen variant #2, uncapped vincristine===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Zinzani et al. 2004	1999-2002 	Phase 3 (C)	FM 	Lower CR rate
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 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
====Subsequent treatment====
*Zinzani et al. 2004, patients with PR or CR with detectable bcl-2/IgH fusion by PCR: R consolidation x 4
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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. link to original article EuroPMC 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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==CHOP-B==
CHOP-B: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne, Bleomycin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Peterson et al. 2003 (CALGB 7951)	1980-1985 	Phase 3 (E-esc)	Cyclophosphamide	Did not meet primary endpoint of OS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
*Bleomycin (Blenoxane) as follows:
**Cycles 1 to 6: 10 units/m2 IM once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
21-day cycle for 6 cycles, then 28-day cycles up to 2 years beyond maximal response
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==CHOP, then 131Iodine-Tositumomab==
CHOP-RIT: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne RadioImmunoTherapy
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Press et al. 2003 (SWOG S9911)	1999-2000 	Phase 2 	 	
Press et al. 2012 (SWOG S0016)	2001-2008 	Phase 3 (E-switch-ooc)	R-CHOP 	Longer PFS1 (co-primary endpoint)
1Reported efficacy for SWOG S0016 is based on the 2018 update.
===Induction===
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
====Supportive therapy====
*Allopurinol (Zyloprim) 300 mg PO once per day for patients with bulky disease
21-day cycle for 6 cycles, followed by:
===Consolidation===
====Radioconjugate therapy, dosimetric step====
*On Day 1, infusions of:
**Tositumomab 450 mg IV over 1 hour
**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 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
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00003784
## Update: Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, Leblanc M, Fisher RI; 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. link to original article EuroPMC
# 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. link to original article contains partial protocol link to PMC article EuroPMC 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. link to original article link to PMC article EuroPMC
==CHVP==
CHVP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vumon (Teniposide), Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Solal-Celigny et al. 1993 (GELA GELF-86)	1986-1991 	Phase 3 (C)	CHVP-I 	Seems to have shorter OS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
*Teniposide (Vumon) 60 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
1-month cycle for 6 cycles
====Subsequent treatment====
*GELA GELF-86, SD or better: CHVP maintenance
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==CHVP-I==
CHVP-I: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vumon (Teniposide), Prednisone, Interferon alfa-2b
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Solal-Celigny et al. 1993 (GELA GELF-86)	1986-1991 	Phase 3 (E-RT-esc)	CHVP 	Seems to have longer OS
Deconinck et al. 2005 (GOELAMS 064) 	1994-2001 	Phase 3 (C) 	VCAP, then HDT	Seems to have shorter EFS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
*Teniposide (Vumon) 60 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
====Immunotherapy====
*Interferon alfa-2b (Intron-A) 5,000,000 units SC three times per week
1-month cycle for 6 cycles, then 2-month cycle for 6 cycles
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC 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. link to original article EuroPMC
==CHVP-I (Etoposide)==
CHVP-I: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), VP-16 (Etoposide), Prednisolone, Interferon alfa-2a
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Salles et al. 2008 (FL2000)	2000-2002 	Phase 3 (C)	R-CHVP+I 	Shorter EFS (primary endpoint)
Note: Interferon was continued for a full 18 months. To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisolone (Millipred) 40 mg/m2 PO once per day on days 1 to 5
====Immunotherapy====
*Interferon alfa-2a (Roferon-A) by the following age-based criteria:
**Younger than 70 years old: 4,500,000 units SC three times per week
**Older than 70 years old: 3,000,000 units SC three times per week
28-day cycle for 6 cycles, then 56-day cycle for 6 cycles (see note)
===References===
#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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC 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. 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. link to original article link to PMC article EuroPMC
==CHVP-I (Prednisolone)==
CHVP-I: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vumon (Teniposide), Prednisolone, Interferon alfa-2b
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Sebban et al. 2006 (GELA GELF-94)	1994-2001 	Phase 3 (C)	CHOP, then HDT	Did not meet primary endpoint of EFS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
*Teniposide (Vumon) 60 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisolone (Millipred) 40 mg/m2 PO once per day on days 1 to 5
====Immunotherapy====
*Interferon alfa-2b (Intron-A) 5,000,000 units SC three times per week
1-month cycle for 6 cycles, then 2-month cycle for 6 cycles
===References===
# 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. link to original article EuroPMC NCT00140569
==CVP, then 131Iodine-Tositumomab==
CVP-RIT: Cyclophosphamide, Vincristine, Prednisone, then RadioImmunoTherapy
Study 	Dates of enrollment	Evidence
Link et al. 2010	2000-07 to 2001-06 	Phase 2
===Induction===
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 400 mg/m2 PO once per day on days 1 to 5
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
21-day cycle for 6 cycles, followed within 56 days by:
===Consolidation===
====Radioconjugate therapy, dosimetric step====
*On Day 1, infusions of:
**Tositumomab 450 mg IV over 1 hour
**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, dosimetric step====
*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 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, therapeutic step====
*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
===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. link to original article EuroPMC.
==Fludarabine, then 131Iodine-Tositumomab==
Study 	Dates of enrollment	Evidence
Leonard et al. 2005	1998-08 to 1999-06 	Phase 2
===Induction===
====Chemotherapy====
*Fludarabine (Fludara) 25 mg/m2 IV once per day on days 1 to 5
35-day cycle for 3 cycles, followed by:
===Consolidation===
====Radioconjugate therapy, dosimetric step====
*On Day 0, infusions of:
**Tositumomab 450 mg IV over 1 hour
**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 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
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==FM==
FM: Fludarabine, Mitoxantrone
===Regimen variant #1, 75/10, IV fludarabine===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Zinzani et al. 2004	1999-2002 	Phase 3 (E-switch-ic)	CHOP 	Higher CR rate (primary endpoint)
====Chemotherapy====
*Fludarabine (Fludara) 25 mg/m2 IV once per day on days 1 to 3
*Mitoxantrone (Novantrone) 10 mg/m2 IV once on day 1
21-day cycle for 6 cycles
====Subsequent treatment====
*Zinzani et al. 2004, patients with PR or CR with detectable bcl-2/IgH fusion by PCR: R consolidation x 4
===Regimen variant #2, 100/10, IV fludarabine===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Foussard et al. 2005	1995-1999 	Phase 3 (E-switch-ic)	mini-CHVP 	Longer FFS
====Chemotherapy====
*Fludarabine (Fludara) 20 mg/m2 IV once per day on days 1 to 5
*Mitoxantrone (Novantrone) 10 mg/m2 IV once on day 1
28-day cycle for 6 cycles
====Subsequent treatment====
*FM consolidation
===Regimen variant #3, 120/10, PO fludarabine===
Study 	Evidence	Efficacy
Zinzani et al. 2008 (FLUMIZ)	Phase 2 	ORR: 98%
====Chemotherapy====
*Fludarabine (Fludara) 40 mg/m2 PO once per day on days 1 to 3
*Mitoxantrone (Novantrone) 10 mg/m2 IV once on day 1
====Supportive therapy====
*Allopurinol (Zyloprim) 300 mg PO once per day for patients with bulky disease
28-day cycle for 6 cycles
====Subsequent treatment====
*Patients were restaged 4 to 6 weeks after finishing cycle 6.
*FLUMIZ, at least a partial response (PR), ANC greater than 1500/μL, platelet count greater than 100 x 109/L, and less than 25% bone marrow involvement were eligible for: ibritumomab tiuxetan consolidation, 6 to 10 weeks after the end of cycle 6.
====Dose and schedule modifications====
*G-CSF could be used for later cycles at physician discretion if grade 3 or 4 neutropenia or delayed neutropenic fever occurred.
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# 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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC EudraCT 2004-002211-92
==131Iodine-Tositumomab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Kaminski et al. 2005	1996-06 to 1999-04 	Phase 2
Note: Calculated dose of I-131 is based on information from serial total-body gamma-camera counts
====Radioconjugate therapy, dosimetric step====
*On Day 0, infusions of:
**Tositumomab 450 mg IV over 1 hour
**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====
*Tositumomab 450 mg IV over 60 minutes on any day from 7 to 14
*Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 by the following laboratory-based criteria:
**Platelet count 150 x 109/L or more: A dose that will provide 75 cGy of radiation to the total body IV over 20 minutes on any day from 7 to 14
**Platelet count 100 x 109/L to 150 x 109/L: A dose that will provide 65 cGy of radiation to the total body IV over 20 minutes on any day from 7 to 14
One course
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## 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.
</div>
==MCP==
MCP: Mitoxantrone, Chlorambucil, Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Nickenig et al. 2006 (GLSG '96)	1996-1998 	Phase 3 (E-switch-ic)	CHOP 	Might have lower CR rate
Note: the chlorambucil dose is written in the reference as "3 x 3 mg/m2"; total dose per day is 9 mg/m2.
====Chemotherapy====
*Mitoxantrone (Novantrone) 8 mg/m2 IV once per day on days 1 & 2
*Chlorambucil (Leukeran) 3 mg/m2 PO three times per day on days 1 to 5
====Glucocorticoid therapy====
*Prednisone (Sterapred) 25 mg/m2 PO once per day on days 1 to 5
28-day cycle for 6 to 8 cycles
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==MCP (Prednisolone)==
MCP: Mitoxantrone, Chlorambucil, Prednisolone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Herold et al. 2007 (OSHO-39)	1998-2003 	Phase 3 (C)	R-MCP 	Shorter OS
Note: the chlorambucil dose is written in the reference as "3 x 3 mg/m2"; total dose per day is 9 mg/m2.
====Chemotherapy====
*Mitoxantrone (Novantrone) 8 mg/m2 IV once per day on days 1 & 2
*Chlorambucil (Leukeran) 3 mg/m2 PO three times per day on days 1 to 5
====Glucocorticoid therapy====
*Prednisolone (Millipred) 25 mg/m2 PO once per day on days 1 to 5
28-day cycle for up to 8 cycles
====Subsequent treatment====
*OSHO-39, patients who achieved a PR or CR: Interferon alfa-2a maintenance, within 4 to 8 weeks of completion of chemotherapy
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC 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. link to original article EuroPMC
=Consolidation after first-line therapy=
==131Iodine-Tositumomab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Friedberg et al. 2014 (SWOG S0433)	2005-11 to 2010-03 	Phase 2
Will be added if drug is ever returned to market.
====Preceding treatment====
*Induction R-CHOP
====Radioconjugate therapy====
*Tositumomab and I-131 (Bexxar)
===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. link to original article link to PMC article does not contain dosing details EuroPMC NCT00107380
=Maintenance after first-line therapy=
==Interferon alfa-2a monotherapy==
===Regimen variant #1, 3 MU TIW===
Study 	Dates of enrollment	Evidence
Salles et al. 2008 (FL2000)	2000-2002 	Non-randomized part of phase 3 RCT
Note: This variant was intended for patients older than 70 years.
====Preceding treatment====
*Induction R-CHVP+I versus CHVP+I
====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)
===Regimen variant #2, 4.5 MU TIW x 18 mo===
Study 	Dates of enrollment	Evidence
Salles et al. 2008 (FL2000)	2000-2002 	Non-randomized part of phase 3 RCT
Note: This variant was intended for patients younger than 70 years.
====Preceding treatment====
*Induction R-CHVP+I versus CHVP+I
====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)
===Regimen variant #3, 4.5 MU TIW, indefinitely===
Study 	Dates of enrollment	Evidence
Herold et al. 2007 (OSHO-39)	1998-2003 	Non-randomized part of phase 3 RCT
====Preceding treatment====
*Induction MCP versus R-MCP
====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
===Regimen variant #4, 5 MU TIW===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Lenz et al. 2004	1996-2000 	Phase 3 (C)	Cy/TBI, then auto HSCT	Shorter PFS
====Preceding treatment====
*Induction CHOP or MCP
====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
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC 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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC 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. link to original article link to PMC article EuroPMC
=Relapsed or refractory=
==CHOP==
CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Van Oers et al. 2006 (EORTC 20981)	1998-2004 	Phase 3 (C)	R-CHOP 	Might have shorter OS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 6 cycles
====Subsequent treatment====
*EORTC 20981, responders (PR or CR): Rituximab maintenance versus no further treatment
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC 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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
==FCM==
FCM: Fludarabine, Cyclophosphamide, Mitoxantrone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Forstpointner et al. 2004	1998-2001 	Phase 3 (C)	R-FCM 	Seems to have shorter PFS
====Chemotherapy====
*Fludarabine (Fludara) 25 mg/m2 IV over 30 minutes once per day on days 1 to 3
*Cyclophosphamide (Cytoxan) 200 mg/m2 IV over 4 hours on days 1 to 3
*Mitoxantrone (Novantrone) 8 mg/m2 IV over 30 minutes once on day 1
28-day cycle for 4 cycles
====Subsequent treatment====
*Forstpointner et al. 2004, responders (PR or CR): Rituximab maintenance versus no further treatment
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## 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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Ofatumumab monotherapy==
===Regimen=== 
Study 	Dates of enrollment	Evidence
Hagenbeek et al. 2008 (Hx-CD20-001)	2004-2005 	Phase 1/2
Czucman et al. 2012 (405 Study) 	2006-2008 	Phase 2
Note: there was no MTD determined in Hx-CD20-001.
====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
*Cetirizine (Zyrtec) 10 mg (or equivalent) PO before each dose of ofatumumab
*Prednisolone (Millipred) (or equivalent) 100 mg before dose 1 and 2 of ofatumumab
28-day cycle for 2 cycles
===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. link to original article EuroPMC 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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00394836
Category:Follicular lymphoma regimens
Category:Historical regimens
Category:Disease-specific pages
Category:Indolent lymphomas
Category:B-cell lymphomas