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Revision as of 13:01, 24 January 2018
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Use of this site is subject to you reading and agreeing with the terms set forth in the disclaimer. If this is your first time visiting, we suggest you read the tutorial.
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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 NCCN Guidelines. Is there a regimen missing from this list? Please go to the main follicular lymphoma regimen page to find other regimens.
30 regimens on this page
38 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
CF
back to top |
CF: Cyclophosphamide, Fludarabine
Regimen
Study | Evidence | Comparator |
---|---|---|
Hochster et al. 2009 (ECOG E1496) | Phase III | CVP |
Note: investigation into this regimen was halted due to excess mortality.
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Fludarabine (Fludara) 20 mg/m2 IV once per day on days 1 to 5
28-day cycles
References
- 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. link to original article contains verified protocol PubMed
CHOP
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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Regimen #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hiddemann et al. 2005 | Phase III | R-CHOP | Inferior OS |
Nickenig et al. 2006 | Phase III | MCP | Might have superior CR rate |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
- Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
21-day cycle for 6 to 8 cycles
Regimen #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Zinzani et al. 2004 | Phase III | FM | Equivalent OS |
Chemotherapy, part 1
- 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
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 6 cycles; patients with PR or CR with detectable bcl-2/IgH fusion by PCR received:
Chemotherapy, part 2
- Rituximab (Rituxan) 375 mg/m2 IV once per week on days 1, 8, 15, 22
4-week course
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 contains verified protocol PubMed
- 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 contains verified protocol PubMed
- 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 PubMed
- 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 contains verified protocol PubMed
CHOP-B
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CHOP-B: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Bleomycin
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Peterson et al. 2003 (CALGB 7951) | Phase III | Cyclophosphamide | Seems not superior |
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 per cycle) IV once on day 1
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
- Bleomycin (Blenoxane) 10 units/m2 IM once on day 1
21-day cycle for 6 cycles, then CHOP continues every 4 weeks (see paper for details)
References
- 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 contains verified protocol PubMed
CHOP, then 131Iodine-Tositumomab
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CHOP-RIT: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone RadioImmunoTherapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Press et al. 2003 (SWOG S9911) | Phase II | ||
Press et al. 2012 (SWOG S0016) | Phase III | R-CHOP | Seems not superior |
Chemotherapy, CHOP portion
- 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 per cycle) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications
- Allopurinol (Zyloprim) 300 mg PO once per day for patients with bulky disease
21-day cycle for 6 cycles, followed by:
Tositumomab & I-131 (Bexxar) 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 medications
- Acetaminophen (Tylenol) 650 mg PO as premedication for Tositumomab & I-131 (Bexxar)
- Diphenhydramine (Benadryl) 50 mg PO as premedication for Tositumomab & I-131 (Bexxar)
- Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO TID, Lugol solution 20 drops PO TID, 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
Tositumomab & I-131 (Bexxar) 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 medications
- Acetaminophen (Tylenol) 650 mg PO as premedication for Tositumomab & I-131 (Bexxar)
- Diphenhydramine (Benadryl) 50 mg PO as premedication for Tositumomab & I-131 (Bexxar)
- Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO TID, Lugol solution 20 drops PO TID, 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
- 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 contains verified protocol PubMed
- Update: Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, Leblanc M, Fisher RI; Southwest Oncology Group. 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 PubMed
- 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 PubMed
CHVP
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CHVP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vumon (Teniposide), Prednisone
Regimen
Study | Evidence | Comparator |
---|---|---|
Solal-Celigny et al. 1993 (GELF-86) | Phase III | CHVP-I |
Chemotherapy
References
- Solal-Celigny P, Lepage E, Brousse N, Reyes F, Haioun C, Leporrier M, Peuchmaur M, Bosly A, Parlier Y, Brice P, et al. Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. Groupe d'Etude des Lymphomes de l'Adulte. N Engl J Med. 1993 Nov 25;329(22):1608-14. link to original article PubMed
CHVP-I
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CHVP-I: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vumon (Teniposide), Prednisone, Interferon alfa-2b
Regimen
Study | Evidence | Comparator |
---|---|---|
Solal-Celigny et al. 1993 (GELF-86) | Phase III | CHVP |
Sebban et al. 2006 (GELF-94) | Phase III | CHOP, then HDT |
Chemotherapy
- Cyclophosphamide (Cytoxan)
- Doxorubicin (Adriamycin)
- Teniposide (Vumon)
- Prednisone (Sterapred)
- Interferon alfa-2b (Intron-A)
References
- Solal-Celigny P, Lepage E, Brousse N, Reyes F, Haioun C, Leporrier M, Peuchmaur M, Bosly A, Parlier Y, Brice P, et al. Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. Groupe d'Etude des Lymphomes de l'Adulte. N Engl J Med. 1993 Nov 25;329(22):1608-14. link to original article PubMed
- 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 PubMed
CVP
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CVP: Cyclophosphamide, Vincristine, Prednisone
COP
COP protocol 2
VCP
Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Marcus et al. 2005 | Phase III | R-CVP | Inferior TTP | Similar toxicity |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
21-day cycle for up to 8 cycles
References
- 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. link to original article contains protocol 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. link to original article PubMed
CVP, then 131Iodine-Tositumomab
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CVP-RIT: Cyclophosphamide, Vincristine, Prednisone, then RadioImmunoTherapy
Regimen
Study | Evidence |
---|---|
Link et al. 2010 | Phase II |
Chemotherapy, CVP portion
- 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 per cycle) IV once on day 1
- 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:
Tositumomab & I-131 (Bexxar) 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 medications
- Acetaminophen (Tylenol) 650 mg PO as premedication for Tositumomab & I-131 (Bexxar)
- Diphenhydramine (Benadryl) 50 mg PO as premedication for Tositumomab & I-131 (Bexxar)
- Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO TID, Lugol solution 20 drops PO TID, 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
Tositumomab & I-131 (Bexxar) 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 medications
- Acetaminophen (Tylenol) 650 mg PO as premedication for Tositumomab & I-131 (Bexxar)
- Diphenhydramine (Benadryl) 50 mg PO as premedication for Tositumomab & I-131 (Bexxar)
- Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO TID, Lugol solution 20 drops PO TID, 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 PubMed.
Fludarabine, then 131Iodine-Tositumomab
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Regimen
Study | Evidence |
---|---|
Leonard et al. 2005 | Phase II |
Chemotherapy
- Fludarabine (Fludara) 25 mg/m2 IV once per day on days 1 to 5
35-day cycle for 3 cycles, followed by:
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
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 contains verified protocol PubMed
FM
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FM: Fludarabine, Mitoxantrone
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Zinzani et al. 2004 | Phase III | CHOP | Equivalent OS |
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
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 contains verified protocol PubMed
FND
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FND: Fludarabine, Novantrone (Mitoxantrone), Dexamethasone
Regimen
Study | Evidence |
---|---|
McLaughlin et al. 1996 | Phase II |
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
- Dexamethasone (Decadron) 20 mg/day PO/IV on days 1 to 5
28-day cycle for up to 8 cycles
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. link to original article PubMed
131Iodine-Tositumomab monotherapy
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Regimen
Study | Evidence |
---|---|
Kaminski et al. 2005 | Phase II |
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
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
- 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 contains verified protocol PubMed
- Update: 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
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MCP: Mitoxantrone, Chlorambucil, Prednisolone
Regimen #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Nickenig et al. 2006 | Phase III | CHOP | Might have inferior CR rate |
Chemotherapy
- Mitoxantrone (Novantrone) 8 mg/m2 IV once per day on days 1 & 2
- Chlorambucil (Leukeran) 3 mg/m2 PO TID (written in the reference as "3 x 3 mg/m2"; total daily dose is 9 mg/m2) on days 1 to 5
- Prednisone (Sterapred) 25 mg/m2 PO once per day on days 1 to 5
28-day cycle for 6 to 8 cycles
Regimen #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Herold et al. 2007 (OSHO #39) | Phase III | R-MCP | Inferior OS |
Chemotherapy
- Mitoxantrone (Novantrone) 8 mg/m2 IV once per day on days 1 & 2
- Chlorambucil (Leukeran) 3 mg/m2 PO TID (written in the reference as "3 x 3 mg/m2"; total daily dose is 9 mg/m2) on days 1 to 5
- Prednisolone (Millipred) 25 mg/m2 PO once per day on days 1 to 5
28-day cycle for up to 8 cycles
All patients who achieved a PR or CR were placed on maintenance interferon alfa-2a within 4 to 8 weeks of completion of chemotherapy.
References
- 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 contains verified protocol PubMed
- 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 contains verified protocol PubMed
- 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 PubMed
ProMACE-MOPP
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ProMACE-MOPP: Prolix (Prednisone), Methotrexate, Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide, Mustargen (Mechlorethamine), Oncovin (Vincristine), Procarbazine, Prednisone
Regimen
Study | Evidence | Comparator |
---|---|---|
Young et al. 1988 | Phase III | Observation |
Chemotherapy
- Prednisone (Prolix)
- Methotrexate (MTX)
- Doxorubicin (Adriamycin)
- Cyclophosphamide (Cytoxan)
- Etoposide (Vepesid)
- Mechlorethamine (Mustargen)
- Vincristine (Oncovin)
- Procarbazine (Matulane)
- Prednisone (Sterapred)
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. PubMed
Consolidation after first-line therapy
131Iodine-Tositumomab monotherapy
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Regimen
Study | Evidence |
---|---|
Friedberg et al. 2014 (SWOG S0433) | Phase II |
Will be added if drug is ever returned to market.
=Preceding treatment
References
- 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 PMC article PubMed
Relapsed or refractory
CHOP
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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Van Oers et al. 2006 (EORTC 20981) | Phase III | R-CHOP | Inferior PFS |
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 per cycle) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 6 cycles
Responders (PR or CR) were randomized to maintenance rituximab or no further treatment.
References
- 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 contains verified protocol PubMed
- 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 contains verified protocol PubMed
References
- Ahmadi T, Chong EA, Gordon A, Aqui NA, Nasta SD, Svoboda J, Mato AR, Schuster SJ. Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant indolent and mantle cell lymphomas. Cancer. 2014 Jan 15;120(2):222-8. Epub 2013 Oct 7. link to original article contains protocol PubMed
FCM
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FCM: Fludarabine, Cyclophosphamide, Mitoxantrone
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Forstpointner et al. 2004 | Phase III | R-FCM | Seems to have inferior 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
Responders (PR or CR) were randomized to maintenance rituximab or 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 contains verified protocol 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. link to original article contains verified protocol PubMed
FMP
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FMP: Fludarabine, Mitoxantrone, Prednisone
Regimen
Study | Evidence |
---|---|
Zinzani et al. 1995 | Phase II |
Chemotherapy
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. PubMed
FR
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FR: Fludarabine, Rituximab
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Rummel et al. 2015 (StiL NHL 2-2003) | Phase III | BR | Inferior PFS |
Chemotherapy
- Fludarabine (Fludara) 25 mg/m2 (route not specified) once per day on days 1 to 3
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
28-day cycle for up to 6 cycles
References
- 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. link to original article contains protocol PubMed
131Iodine-Tositumomab monotherapy
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Regimen
Study | Evidence |
---|---|
Kaminski et al. 2001 | Phase II |
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
Therapeutic step
- Any day from day 7 to 15, 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
Supportive medications
- Acetaminophen (Tylenol) 650 mg PO as premedication for Tositumomab & I-131 (Bexxar)
- Diphenhydramine (Benadryl) 50 mg PO as premedication for Tositumomab & I-131 (Bexxar)
- Potassium iodide (SSKI, saturated solution of potassium iodide) 2 drops PO TID 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
References
- 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. link to original article contains verified protocol PubMed
- 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. link to original article PubMed
- 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. PubMed