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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. 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. Please go to the 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.

Untreated

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	Decreased OS
Nickenig et al. 2006	Phase III	MCP	Equivalent OS

• 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 x 6 to 8 cycles

Regimen #2

Study	Evidence	Comparator	Efficacy
Zinzani et al. 2004	Phase III	FM; FMR; R-CHOP	Equivalent OS

• 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 cycles x 6 cycles; patients with PR or CR with detectable bcl-2/IgH fusion by PCR received:

• Rituximab (Rituxan) 375 mg/m2 IV once weekly on days 1, 8, 15, 22

4-week course

References

1. 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
2. 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
3. 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
4. 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	Equivalent OS

• 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

3-week cycle x 6 cycles, then CHOP continues every 4 weeks (see paper for details)

References

1. 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

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

• Cyclophosphamide (Cytoxan)
• Doxorubicin (Adriamycin)
• Teniposide (Vumon)
• Prednisone (Sterapred)

References

1. 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 -> HDT

• Cyclophosphamide (Cytoxan)
• Doxorubicin (Adriamycin)
• Teniposide (Vumon)
• Prednisone (Sterapred)
• Interferon alfa-2b (Intron-A)

References

1. 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
2. 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

Synonyms: COP, COP protocol 2, VCP

Structured Concept: C9573 (NCI-T), C0056633 (NCI-MT/UMLS)

Regimen

Study	Evidence	Comparator	Efficacy	Toxicity
Marcus et al. 2005	Phase III	R-CVP	Worsened OS	Similar toxicity

• 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 cycles x up to 8 cycles

References

1. 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
   1. 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

FM

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FM: Fludarabine, Mitoxantrone

Regimen

Study	Evidence	Comparator	Efficacy
Zinzani et al. 2004	Phase III	CHOP; FMR; R-CHOP	Equivalent OS

• 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 cycles x 6 cycles; patients with PR or CR with detectable bcl-2/IgH fusion by PCR received:

• Rituximab (Rituxan) 375 mg/m2 IV once weekly on days 1, 8, 15, 22

4-week course

References

1. 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

• 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 x up to 8 cycles

References

1. 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

MCP

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MCP: Mitoxantrone, Chlorambucil, Prednisolone

Regimen #1

Study	Evidence	Comparator	Efficacy
Nickenig et al. 2006	Phase III	CHOP	Equivalent OS

• 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 cycles x 6 to 8 cycles

Regimen #2

Study	Evidence	Comparator	Efficacy
Herold et al. 2007 (OSHO #39)	Phase III	R-MCP	Inferior OS

• 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 cycles x 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

1. 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
2. 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
   1. 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

References

1. 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

Relapsed/Refractory

FMP

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FMP: Fludarabine, Mitoxantrone, Prednisone

Regimen

Study	Evidence
Zinzani et al. 1995	Phase II

References

1. 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