Chemoregimen - Lymphoma

Lymphoma

Non-Hodgkin’s lymphoma
Indolent lymphoma
Mantle cell lymphoma
Aggressive lymphoma
Highly aggressive lymphoma

Primary CNS lymphoma

Hodgkin’s disease

ABVD
Doxorubicin (Adriamycin) 25 mg/m2 iv d1 and 15
Bleomycin 10 U/m2 iv d1 and 15
Vinblastine 6 mg/m2 iv d1 and 15
Dacarbazine (DTIC) 375 mg/m2 iv d1 and 15
Q4w

Gianni AM et al. Comparable 3-year outcome following ABVD or BEACOPP first-line chemotherapy, plus pre-planned high-dose salvage, in advanced Hodgkin's lymphoma (HL): a randomized trial of the Michelangelo, GITIL and IIL cooperative groups. 2008 ASCO annual meeting. Abstract 8506 (link to the abstract).

Engert A et al. Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: Final results of the GHSG HD7 trial. J Clin Oncol 2007; 25:3495 (link to the article).

Bonadonna G et al. ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin's disease: long-term results. J Clin Oncol 2004; 22:2835 (link to the article).

Carde, P et al. Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: The H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group. J Clin Oncol 1993; 11:2258 (link to the article).

Canellos GP et al. Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Eng J Med 1992; 327:1478 (link to the article).

BEACOPP
Bleomycin 10 IU/m2 iv d8
Etoposide (VP-16) 100 mg/m2/d iv d1-3
Doxorubicin (Adriamycin) 25 mg/m2 iv d1
Cyclophosphamide (Cytoxan) 650 mg/m2 iv d1
Vincristine 1.4 mg/m2 (max 2 mg) iv d8
Procarbazine 100 mg/m2 po qd d1-7
Prednisone 40 mg/m2 po qd d1-7
Q3w

Dann EJ et al. Risk-adapted BEACOPP regimen can reduce the cumulative dose of chemotherapy for standard and high-risk Hodgkin lymphoma with no impairment of outcome. Blood 2007; 109:905 (link to the article).

Increased-dose BEACOPP
Bleomycin 10 IU/m2 iv d8
Etoposide (VP-16) 200 mg/m2/d iv d1-3
Doxorubicin (Adriamycin) 35 mg/m2 iv d1
Cyclophosphamide (Cytoxan) 1250 mg/m2 iv d1
Vincristine 1.4 mg/m2 (max 2 mg) iv d8
Procarbazine 100 mg/m2 po qd d1-7
Prednisone 40 mg/m2 po qd d1-14
Filgrastim (Neupogen) support
Q3w

Diehl V et al. Ten-year results of a German Hodgkin Study Group randomized trial of standard and increased dose BEACOPP chemotherapy for advanced Hodgkin's lymphoma (HD9). 2007 ASCO annual meeting. Abstract LBA 8015 (link to the abstract).

Diehl V et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Eng J Med 2003; 348:2386 (link to the article).

Stanford V
Nitrogen mustard 6 mg/m2 iv d1
Doxorubicin (Adriamycin) 25 mg/m2 iv d1 and 15
Vinblastine 6 mg/m2 iv d1 and 15
Vincristine 1.4 mg/m2 iv d8 and 22
Bleomycin 5 U/m2 iv d8 and 22
Etoposide (VP-16) 60 mg/m2 iv d15 and 16
Prednisone 40 mg po qod x 10 weeks, then taper by 10 mg every other day between weeks 10 and 12
Q4w x 3 cycles (12 weeks)
For patients older than 50, reduce Vinblastine to 4 mg/m2 amd Vincristine to 1 mg/m2 in cycle 3.
Bactrim DS po bid
Acyclovir 200 mg po tid
Ketoconazole 200 mg po qd
2-4 weeks after chemotherapy, consolidation radiotherapy to 36 Gy for lymph nodes > or equal to 5 cm and/or macroscopic nodules in spleen

Horning SJ et al. Assessment of the Stanfod V regimen consolidative radiotherapy for bulky and advanced Hodgkin’s disease: Eastern Cooperative Oncology Group pilot study E1492. J Clin Oncol 2000; 18:972 (link to the article).

MOPP
Nitrogen mustard 6 mg/m2 iv d1 and 8
Vincristine 1.4 mg/m2 iv d1 and 8
Procarbazine 100 mg/m2 po qd d1-14
Prednisone 40 mg/m2 po qd d1-14
Q4w x 6 cycles

Canellos GP et al. Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Eng J Med 1992; 327:1478 (link to the article).

GVD
For transplant-naive patients:
Gemcitabine (Gemzar) 1000 mg/m2 iv d1, 8
Vinorelbine (Navelbine) 20 mg/m2 iv d1, 8
Pegylated liposomal doxorubicin (Doxil) 15 mg/m2 iv d1, 8
Q3w
For post-transplant patients:
Gemcitabine (Gemzar) 800 mg/m2 iv d1, 8
Vinorelbine (Navelbine) 15 mg/m2 iv d1, 8
Pegylated liposomal doxorubicin (Doxil) 10 mg/m2 iv d1, 8
Q3w

Bartlett NL et al. Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin's lymphoma: CALGB 59804. Ann Oncol 2007; 18:1071 (link to the article).

Rituximab (for relapsed lymphocyte-predominant Hodgkin lymphoma)
Rituximab (Rituxan) 375 mg/m2 iv qw x 4

Schulz H et al. Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group. Blood 2008; 111:109 (link to the article).

Non-Hodgkin’s lymphoma (back to top)

Indolent lymphoma

Chlorambucil
Chlorambucil (Leukeran) 10 mg po qd

Ardeshna, KM et al. Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet 2003; 362:516 (link to the article).

Cyclophosphamide
Cyclophosphamide (Cytoxan) 100 mg/m2 po qd

Peterson, BA et al. Prolonged single-agent versus combination chemotherapy in indolent follicular lymphomas: a study of the cancer and leukemia group B. J Clin Oncol 2003; 21:5 (link to the article).

Fludarabine
Fludarabine 25 mg/m2 iv qd d1-5 q4w

Klasa, RJ et al. 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; 20:4649 (link to the article).

Rituximab
Rituximab (Rituxan)
Regimen 1
375 mg/m2 iv qw x 4 followed by 375 mg/m2 iv q2m x 4

Ghielmini, M et al. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood 2004; 103:4416 (link to the article).

Regimen 2
375 mg/m2 iv qw x 4 followed by 375 mg/m2 iv qw x 4 every 6 months

Hainsworth, JD et al. Maximizing therapeutic benefit of rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin's lymphoma--a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2005; 23:1088 (link to the article).

Bendamustine
Bendamustine (Treanda) 120 mg/m2 iv over 30-60 min d1 and 2
Q3w x 12 cycles

Friedberg JW et al. Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: results from a phase II multicenter, single-agent study. J Clin Oncol 2008; 26:204 (link to the article).

Oxaliplatin (for MALT lymphoma)
Oxaliplatin (Eloxatin) 130 mg/m2 iv over 2 hours
Q3w x 6 cycles

Raderer M et al. Phase II study of oxaliplatin for treatment of patients with mucosa-associated lymphoid tissue lymphoma. J Clin Oncol 2005; 23:8442 (link to the article).

CVP
Regimen 1
Cyclophosphamide (Cytoxan) 750 mg/m2 iv d1
Vincristine 1.4 mg/m2 ( max 2 mg ) iv d1
Prednisone 40 mg/m2 po qd d1-5
Q3w x 8 cycles

Marcus, R et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 2005; 105:1417 (link to the article).

Regimen 2
Cyclophosphamide (Cytoxan) 1000 mg/m2 iv d1
Vincristine 1.4 mg/m2 ( max 2 mg ) iv d1
Prednisone 100 mg po qd d1-5
Q3w x 6-8 cycles

Hochster HS et al. Maintenance rituximab after CVP results in superior clinical outcome in advanced follicular lymphoma (FL): results of the E1496 phase III trial from the Eastern Cooperative Oncology Group and the Cancer and Leukemia Group B. 2005 ASH annual meeting. Abstract 349 (link to the abstract).

R-CVP
Rituximab (Rituxan) 375 mg/m2 iv d1
Cyclophosphamide (Cytoxan) 750 mg/m2 iv d1
Vincristine 1.4 mg/m2 ( max 2 mg ) iv d1
Prednisone 40 mg/m2 po qd d1-5
Q3w x 8 cycles

Marcus RE et al. MabTher (rituximab) plus cyclophosphamide, vincristine and prednisone (CVP) chemotherapy improves survival in previously untreated patients with advanced follicular non-hodgkin's lymphoma (NHL). 2006 ASH annual meeting. Abstract 481 (link to the abstract).

Marcus RE et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 2005; 105:1417 (link to the article).

CVP + maintenance R
Cyclophosphamide (Cytoxan) 1000 mg/m2 iv d1
Vincristine 1.4 mg/m2 ( max 2 mg ) iv d1
Prednisone 100 mg po qd d1-5
Q3w x 6-8 cycles
Followed by
Rituximab (Rituxan) 375 mg/m2 iv qw x 4, q6m x 4 (2 years)

CHOP
Cyclophophamide (Cytoxan) 750 mg/m2 iv d1
Doxorubicin (Adriamycin) 50 mg/m2 iv d1
Vincristine 1.4 mg/m2 ( max 2 mg ) iv d1
Prednisone 100 mg po qd d1-5
Q3w x 6-8 cycles

Czuczman, MS et al. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol 2004; 23:4711 (link to the article).

R-CHOP
Rituximab (Rituxan) 375 mg/m2 iv d1
Cyclophophamide (Cytoxan) 750 mg/m2 iv d1
Doxorubicin (Adriamycin) 50 mg/m2 iv d1
Vincristine 1.4 mg/m2 ( max 2 mg ) iv d1
Prednisone 100 mg po qd d1-5
Q3w x 6-8 cycles

Buske C et al. Front-line combined immuno-chemotherapy (R-CHOP) significantly improves the time to treatment failure and overall survival in elderly patients with advanced stage follicular lymphoma-results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). 2006 ASH annual meeting. Abstract 482 (link to the abstract).

R→R-CVP or R-CHOP
Rituximab (Rituxan) 375 mg/m2 iv qw x 4
Followed by
R-CVP or R-CHOP q3w x 3 cycles

Hainsworth, JD et al. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the minnie pearl cancer research network. J Clin Oncol 2005; 23:1500 (link to the article).

R-CHOP + maintenance R
R-CHOP x 6 cycles, followed by Rituximab (Rituxan) 375 mg/m2 iv q3m x 2 yrs

van Oers MHJ et al. 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; 108:3295 (link to the article).

FM
Fludarabine 25 mg/m2 iv qd d1-3
Mitoxantrone (Novantrone) 10 mg/m2 iv d1
Q3w

Zinzani, PL et al. 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; 22:2654 (link to the article).

R-FCM
Rituximab (Rituxan) 375 mg/m2 iv d0
Fludarabine 25 mg/m2 iv over 30 min qd d1-3
Cyclophosphamide (Cytoxan) 200 mg/m2 iv over 4 hrs qd d1-3
Mitoxantrone (Novantrone) 8 mg/m2 iv over 30 min d1
Q4w x 4 cycles

Forstpointner, R et al. 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; 104:3064 (link to the article).

R-FCM + maintenance R
R-FCM as above, followed by Rituximab (Rituxan) 375 mg/m2 iv qw x 4 doses at 3 and 9 months

Forstpointner R et al. 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; 108:4003 (link to the article).

R-MCP
Rituximab (Rituxan) 375 mg/m2 iv d1
Mitoxantrone (Novantrone) 8 mg/m2 iv d3-4
Chlorambucil (Leukeran) 3 mg/m2 po tid d3-7
Prednisone 25 mg/m2 po qd d3-7
Q4w x 8 cycles

Herold M et al. 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; 25:1986 (link to the article).

R-GemOx
Rituximab (Rituxan) 375 mg/m2 iv d1
Gemcitabine (Gemzar) 1000 mg/m2 (in 500 ml normal saline) iv at 10 mg/m2/min d2
Oxaliplatin (Eloxatin) 100 mg/m2 iv over 2 hrs d2
Q2w x 8 cycles

Gnaoui TE et al. Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy. Ann Oncol 2007; Advanced access published May 11, 2007 (link to the article).

Mantle cell lymphoma (back to top)

R-CHOP
Rituximab (Rituxan) 375 mg/m2 iv d0
Cyclophophamide (Cytoxan) 750 mg/m2 iv d1
Doxorubicin (Adriamycin) 50 mg/m2 iv d1
Vincristine 1.4 mg/m2 ( max 2 mg ) iv d1
Prednisone 100 mg po qd d1-5
Q3w x 6 cycles

Lenz G et al. Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves responses and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol 2005; 23:1984 (link to the article).

Bortezomib
Bortezomib (Velcade) 1.3-1.5 mg/m2 iv d1, 4, 8 and 11
Q3w

Approved by FDA on 12/8/06 (link to FDA file).

Strauss SJ et al. Bortezomib therapy in patients with relapsed or refractory lymphoma: potential correlation of in vitro sensitivity and tumor necrosis factor alpha response with clinical activity. J Clin Oncol 2006; 24:2105 (link to the article).

Goy, A et al. Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma. J Clin Oncol 2005; 23:667 (link to the article).

O'Connor, OA et al. Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol 2005; 23:676 (link to the article).

R-GemOx
Rituximab (Rituxan) 375 mg/m2 iv d1
Gemcitabine (Gemzar) 1000 mg/m2 (in 500 ml normal saline) iv d1
Oxaliplatin (Eloxatin) 100 mg/m2 iv over 2 hrs d1
Q2-3w x 8 cycles

Rodriguez J et al. Rituximab, gemcitabine and oxaliplatin: an effective regimen in patients with refractory and relapsing mantle cell lymphoma. Leuk Lymphoma 2007; 48:2172 (link to the article).

Rituximab + Thalidomide
Rituximab (Rituxan) 375 mg/m2 iv qw x 4
Thalidomide ((Thalomid) 200 mg po qd x 2 weeks, then 400 mg po qd until disease progression

Kaufmann H et al. Antitumor activity of rituximab plus thalidomide in patients with relapsed/refractory mantle cell lymphoma. Blood 2004; 104:2269 (link to the article).

Rituximab + Lenalidomide
Rituximab (Rituxan) 375 mg/m2 iv qw x 4
Lenalidomide (Revlimid) 20 mg po qd d1-21 q4w until disease progression

Wang M et al. A phase I/II study of lenalidomide (Len) in combination with rituximab (R) in relapsed/refractory mantel cell lymphoma (MCL) with early evidence of efficacy. 2007 ASCO annual meeting. Abstract 8030 (link to the abstract).

Temsirolimus
Regimen 1
Temsirolimus (Torisel) 250 mg iv over 30 min qw for a total of 12 months or 2 months after CR
Premedication Diphenhydramine (Benadryl) 25-50 mg iv

Witzig TE et al. Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol 2005; 23:5347 (link to the article).

Regimen 2
Temsirolimus (Torisel) 25 mg iv qw for a total of 12 months or 2 months after CR
Premedication Diphenhydramine (Benadryl) 25-50 mg iv

Ansell SM et al. Anti-tumor activity of mTOR inhibitor temsirolimus for relapsed mantle cell lymphoma: a phase II trial in the North Central Cancer Treatment Group. 2006 ASCO annual meeting. Abstract 7532 (link to the abstract).

Regimen 3
Temsirolimus (Torisel) 175 mg iv qw x 3, followed by 75 mg iv qw
Premedication Diphenhydramine (Benadryl) 25-50 mg iv

Hess G et al. Phase III study of patients with relapsed, refractory mantle cell lymphoma treated with temsirolimus compared with investigator's choice therapy. 2008 ASCO annual meeting. Abstract 8513 (link to the abstract).

Aggressive lymphoma (back to top)

CHOP
Cyclophophamide (Cytoxan) 750 mg/m2 iv d1
Doxorubicin (Adriamycin) 50 mg/m2 iv d1
Vincristine 1.4 mg/m2 ( max 2 mg ) iv d1
Prednisone 100 mg po qd d1-5
Q3w x 6-8 cycles

Feugier P et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de I’Adulte. J Clin Oncol 2005; 23:4117 (link to the article).

Approved by FDA on 2/10/2006

Habermann TM et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol 2006; 24:3121 (link to the article).

R-CHOP-14
Rituximab (Rituxan) 375 mg/m2 iv d1
Cyclophophamide (Cytoxan) 750 mg/m2 iv d1
Doxorubicin (Adriamycin) 50 mg/m2 iv d1
Vincristine 1.4 mg/m2 ( max 2 mg ) iv d1
Prednisone 100 mg po qd d1-5
Q2w x 6 cycles

Pfreundschuh M et al. Six vs. eight cycles of bi-weekly CHOP-14 with or without Rituximab for elderly patients with diffuse large B-cell lymphoma (DLBCL): results of the completed RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). 2006 ASH annual meeting; Abstract 205 (link to the abstract).

CEPP (non-anthracycline-containing regimen)
Cyclophosphamide (Cytoxan) 600 mg/m2 iv d1 and 8
Etoposide (VP-16) 70 mg/m2/d iv d1-3
Procarbazine 60 mg/m2/d po d1-10
Prednisone 60 mg/m2/d po d1-10
Q4w x 6 cycles

Chao NJ et al. CEPP: an effective and well-tolerated regimen in poor-risk, aggressive non-Hodgkin's lymphoma. Blood 1990; 76:1293 (link to the article).

ICE
regimen 1
Ifosfamide 1000 mg/m2/d iv over 1 h d1-2 (hours 0 and 1)
Etoposide (VP-16) 150 mg/m2/d iv over 11 hrs after ifosfamide d1-2 (hours 1-11)
Carboplatin (Paraplatin) 200 mg/m2/d iv over 1 h after etoposide d1-2 (hours 11-12)
Etoposide (VP-16) 150 mg/m2/d iv over 11 hrs after carboplatin d1-2 (hours 12-24)
Mesna 333 mg/m2 iv 30 minutes before ifosfamide, repeat 4 and 8 hrs after ifosfamide
Q4w x 2 cycles

Fields KK et al. Ifosfamide, carboplatin and etoposide: a new regimen with a broad spectrum of activity. J Clin Oncol 1994; 12:544 (link to the article).

regimen 2
Ifosfamide 5000 mg/m2 mixed with Mesna 5000 mg/m2 iv over 24 hrs d2
Carboplatin (Paraplatin) AUC 5 (max 800mg) iv d2
Etoposide (VP-16) 100 mg/m2/d iv d1-3
Filgrastim (Neupogen) 5 ug/kg sc qd d5-12
Q2w x 3 cycles

Moskowitz, CH et al. Ifosfamide, carboplatin, and etoposide: A highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma. J Clin Oncol 1999; 17:3776 (link to the article).

RICE
Rituximab (Rituxan) 375 mg/m2 iv d1 q2w x 3 cycles
ICE regimen 2 as above

Kewalramani, T et al. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood 2004; 103:3684 (link to the article).

ESHAP
Etoposide (VP-16) 40 mg/m2/d iv over 1 hr d1-4
Methylprednisolone 500 mg/d iv over 15 min d1-5
Cisplatin (CDDP) 25 mg/m2/d civi d1-4
Cytarabine (Ara-C) 2000 mg/m2 iv over 2 hr d5
Q3-4w x 6-8 cycles

Velasquez, WS et al. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol 1994; 12:1169 (link to the article).

EPOCH
Etoposide (VP-16) 50 mg/m2/d civi d1-4
Prednisone 60 mg/m2/d po d1-5
Vincristine 0.4 mg/m2/d civi d1-4
Doxorubicin (Adriamycin) 10 mg/m2/d civi d1-4
Cyclophosphamide (Cytoxan) 750 mg/m2 iv over 15 min d5
Bactrim DS 1 tablet po bid tiw
Filgrastim (Neupogen) 5 mcg/kg sc qd beginining on d6 till ANC > 10,000/uL
Q3w x 6-8 cycles

Wilson WH et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin’s lymphoma. J Clin Oncol 1993; 11:1573 (link to the article).

Gutierrez, M et al. Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas: An 8-year follow-up study of EPOCH. J Clin Oncol 2000; 18:3633 (link to the article).

Dose-adjusted EPOCH
Etoposide (VP-16) 50 mg/m2/d civi d1-4
Prednisone 60 mg/m2/d po d1-5
Vincristine 0.4 mg/m2/d civi d1-4
Doxorubicin (Adriamycin) 10 mg/m2/d civi d1-4
Cyclophosphamide (Cytoxan) 750 mg/m2 iv over 15 min d5
Bactrim DS 1 tablet po bid tiw
Filgrastim (Neupogen) 5 mcg/kg sc qd beginining on d6 till ANC > 5,000/uL
Q3w x 6-8 cycles

Dose-adjustment paradigm based on twice weekly CBC (dose adjustment above starting doses apply to Etoposide (VP-16), Doxorubicin (Adriamycin) and Cyclophosphamide (Cytoxan). dose adjustment below starting dose apply to Cyclophosphamide (Cytoxan) only) :
If nadir ANC > 500/uL, 20% increase in Etoposide (VP-16), Doxorubicin (Adriamycin) and Cyclophosphamide (Cytoxan) above last cycle
If nadir ANC < 500/uL on 1 or 2 measurements, same doses as last cycle
If nadir ANC < 500/uL on at least 3 measurements, or nadir platelet < 25,000/uL on 1 measurement, 20% decrease in Etoposide (VP-16), Doxorubicin (Adriamycin) and Cyclophosphamide (Cytoxan) below last cycle

Wilson WH et al. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood 2002; 99:2685 (link to the article).

MINE
Mesna 1330 mg/m2/d iv over 1 hr with ifosfamide d1-3, then 500 mg po 4 hrs after ifosfamide d1-3
Ifosfamide 1330 mg/m2/d iv over 1 hr d1-3
Mitoxantrone (Novantrone) 8 mg/m2 iv d1
Etoposide (VP-16) 65 mg/m2/d iv over 1 hr d1-3
Q3w

Rodriguez MA et al. A phase II trial of mesna/ifosfamide, mitoxantrone and etoposide for refractory lymphoma. Ann Oncol 1995; 6:609 (link to the article).

Rodriguez, MA et al. Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP. J Clin Oncol 1995; 13:1734 (link to the article).

DHAP
Dexamethasone (Decadron) 40 mg po qd d1-4
Cisplatin (CDDP) 100 mg/m2 iv over 24 hrs d1
Cytarabine (Ara-C) 2000 mg/m2 iv q12 hrs for 2 doses d2
Q3-4w

Velasquez, WS et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose ara-c and dexamethasone (DHAP). Blood 1988; 71:117 (link to the article).

R-GemOx
Rituximab (Rituxan) 375 mg/m2 iv d1
Gemcitabine (Gemzar) 1000 mg/m2 iv d2
Oxaliplatin (Eloxatin) 100 mg/m2 iv over 2 hrs d2
Q2-3w x 8 cycles

Lopez A et al. GEMOX-R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large-cell lymphoma: a phase II study. Eur J Haematol 2008; 80:127 (link to the article).

Highly aggressive lymphoma (back to top)

Burkitt’s lymphoma

CODOX-M/IVAC (for high risk patients: do not meet low risk below)

Cycle 1 and 3 ( CODOX-M )
Cyclophosphamide (Cytoxan) 800 mg/m2 iv d1
Cyclophosphamide (Cytoxan) 200 mg/m2/d iv d2-5
Doxorubicin (Adriamycin) 40 mg/m2 iv d1
Vincristine 1.5 mg/m2 iv d1, 8 for cycle 1 and d1, 8, 15 for cycle 3
Methotrexate (MTX) 1200 mg/m2 iv over 1 h d10, then 240 mg/m2 per hour civi for the next 23 hrs
Leucovorin 50 mg iv q6h begins 36 hrs from the start of MTX till MTX level < 0.05 uM
Filgrastim (Neupogen) begins 24 hrs from the start of Leucovorin till ANC > 1000/mL
CNS prophylaxis:
Intrathecal Cytarabine (Ara-C) 70 mg d1 and 3, Methotrexate (MTX) 12 mg d15
CNS treatment:
Cycle 1: Intrathecal Cytarabine (Ara-C) 70 mg d1, 3 and 5, Methotrexate (MTX) 12 mg d15 and 17
Cycle 3: Intrathecal Cytarabine (Ara-C) 70 mg d1 and 3, Methotrexate (MTX) 12 mg d15

Cycle 2 and 4 ( IVAC )
Ifosfamide 1500 mg/m2/d iv d1-5
Etoposide (VP-16) 60 mg/m2/d iv d1-5
Cytarabine (Ara-C) 2000 mg/m2 iv q12h d1 and 2 (total 4 doses)
Filgrastim (Neupogen) begins 24 hrs after completion of chemotherapy till ANC > 1000/mL
CNS prophylaxis:
Intrathecal Methotrexate (MTX) 12 mg d5
CNS treatment:
Cycle 2: Intrathecal Methotrexate (MTX) 12 mg d5, Cytarabine (Ara-C) 70 mg d7 and 9
Cycle 4: Intrathecal Methotrexate (MTX) 12 mg d5

Radiotherapy for CNS disease and testicular involvement

Modified CODOX-M (for low risk patients: single extraabdominal mass or completely resected abdominal mass and normal serum LDH)

Cyclophosphamide (Cytoxan) 800 mg/m2 iv d1
Cyclophosphamide (Cytoxan) 200 mg/m2/d iv d2-5
Doxorubicin (Adriamycin) 40 mg/m2 iv d1
Vincristine 1.5 mg/m2 iv d1, 8
Methotrexate (MTX) 1200 mg/m2 iv over 1 h d10, then 240 mg/m2 per hour civi for the next 23 hrs
Leucovorin 50 mg iv q6h begins 36 hrs from the start of MTX till MTX level < 0.05 uM
Filgrastim (Neupogen) begins 24 hrs from the start of Leucovorin till ANC > 1000/mL
CNS prophylaxis:
Intrathecal Cytarabine (Ara-C) 70 mg d1, Methotrexate (MTX) 12 mg d3
Total of 3 cycles

Magrath, I et al. Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol 1996; 14:925 (link to the article).

CALGB 9251

Cycle 1
Cyclophosphamide (Cytoxan) 200 mg/m2/d iv d1-5
Prednisone 60 mg/m2/d po d1-7

Cycle 2, 4, 6
Ifosfamide 800 mg/m2/d iv over 1 hr d1-5
Mesna 200 mg/m2 iv at 0, 4 and 8 hrs after ifosfamide d1-5
Methotrexate (MTX) 150 mg/m2 iv over 30 minutes d1, followed by 1350 mg/m2 civi over 23.5 hrs
Leucovorin 50 mg/m2 iv 36 hrs after start of MTX, followed by 15 mg/m2 iv q6h till MTX level < 0.05 uM
Vincristine 2 mg iv d1
Cytarabine (Ara-c) 150 mg/m2/d civi d 4 and 5
Etoposide (VP-16) 80 mg/m2/d iv over 1 hr d 4 and 5
Dexamethasone (Decadron) 10 mg/m2/d po d1-5

Cycle 3, 5, 7
Cyclophosphamide (Cytoxan) 200 mg/m2/d iv d1-5
Methotrexate (MTX) 150 mg/m2 iv over 30 minutes d1, followed by 1350 mg/m2 civi over 23.5 hrs
Leucovorin 50 mg/m2 iv 36 hrs after start of MTX, followed by 15 mg/m2 iv q6h till MTX level < 0.05 uM
Vincristine 2 mg iv d1
Doxorubicin (Adriamycin) 25 mg/m2/d iv bolus d 4 and 5
Dexamethasone (Decadron) 10 mg/m2/d po d1-5
Intrathecal (cycle 2-7)
Methotrexate (MTX) 15 mg d1
Cytarabine (Ara-c) 40 mg d1
Hydrocortisone 50 mg d1
Brain radiation 24 Gy post chemotherapy if bone marrow involvement
Start cycle 2 right after cycle 1, cycle 2-7 are given q3w

Rizzieri, DA et al. Intensive chemotherapy with and without cranial radiation for Burkitt leukemia and lymphoma: final results of Cancer and Leukemia Group B Study 9251. Cancer 2004; 100:1438 (link to the article).

Lee EJ et al. Brief-duration high-intensity chemotherapy for patients with small noncleaved -cell lymphoma or FAB L3 acute lymphocytic leukemia: results of Cancer and Leukemia Group B Study 9251. J Clin Oncol 2001; 19:4014 (link to the article).

Pre-B or T lymphoblastic lymphoma

Hyper-CVAD/MTX-Ara-C

Cycle 1,3,5,7 (3-4 wks/cycle)
Cyclophosphamide (Cytoxan) 300 mg/m2 iv over 2 hrs q12 hrs x 6 doses d1-3
Mesna 600 mg/m2/d civi d1-3 to start 1 h before cyclophosphamide till 12 hrs after completion of cyclophosphamide
Vincristine 2 mg iv d4, 11
Doxorubicin (Adriamycin) 50 mg/m2 iv over 24 hrs (over 48 hrs if LVEF < 50%) d4
Dexamethasone (Decadron) 40 mg po or iv qd d1-4 and d11-14

Cycle 2,4,6,8 (3-4 wks/cycle)
Methotrexate (MTX) 200 mg/m2 iv over 2 hrs followed by 800 mg/m2 civi over 22 hrs d1
Cytarabine (Ara-C) 3 g/m2 (1 g/m2 for patients over 60 years old) iv over 2 hrs q12 hrs x 4 doses d2-3
Leucovorin 50 mg iv q6 hrs starting 12 hrs after completion of MTX till MTX level < 0.05 uM

Intrathecal chemotherapy
Prophylaxis
Methotrexate (MTX) 12 mg d2 of each cycle for a total of 3-4 treatments
Cytarabine (Ara-C) 100 mg d8 of each cycle for a total of 3-4 treatments
Therapeutic
Intrathecal chemotherapy twice a week (Methotrexate (MTX) 12 mg and Cytarabine (Ara-C) 100 mg respectively) till no more cancer cells in CSF, then decrease intrathecal chemotherapy to once a week x 4, followed by Methotrexate (MTX) 12 mg d2, Cytarabine (Ara-C) 100 mg d8 for the remaining chemotherapy cycles

Cranial radiotherapy 24-30 Gy if cranial nerve palsies

Thomas, DA et al. Outcome with the hyper-CVAD regimens in lymphoblastic lymphoma. Blood 2004; 104:1624 (link to the article).

CALGB 9111

Cycle 1 (4 wks)
Cyclophosphamide (Cytoxan) 1200 mg/m2 iv d1
Doxorubicin (Adriamycin) 45 mg/m2/d iv d1, 2, 3
Vincristine 2 mg iv d1, 8, 15, 22
Prednisone 60 mg/m2 po or iv qd d1-21
L-Asparaginase 6000 IU/m2 sc or im d5, 8, 11, 15, 18, 22
Reduce doses if patients older than 60:
Cyclophosphamide (Cytoxan) 800 mg/m2 iv d1
Doxorubicin (Adriamycin) 30 mg/m2/d iv d1, 2, 3
Prednisone 60 mg/m2 po qd d1-7
Filgrastim (Neupogen) 5 mcg/kg sc qd d4 till ANC > 1000/uL

Cycle 2 (4 wks,repeat once)
Cyclophosphamide (Cytoxan) 1000 mg/m2 iv d1
6-Mercaptopurine (6-MP) 60 mg/m2/d po d1-14
Cytarabine (Ara-C) 75 mg/m2/d sc d1-4 and 8-11
Vincristine 2 mg iv d15, 22
L-Asparaginase 6000 IU/m2 sc or im d15, 18, 22, 25
Intrathecal Methotrexate (MTX) 15 mg d1
Filgrastim (Neupogen) 5 mcg/kg sc qd d2 till ANC > 5000/uL

Cycle 3 (12 wks)
6-Mercaptopurine (6-MP) 60 mg/m2/d po d1-70
Methotrexate (MTX) 20 mg/m2 po d36, 43, 50, 57, 64
Intrathecal Methotrexate (MTX) 15 mg d1, 8, 15, 22, 29
Brain radiation 24 Gy d1-12

Cycel 4 (8 wks)
Doxorubicin (Adriamycin) 30 mg/m2/d iv d1, 8, 15
Vincristine 2 mg iv d1, 8, 15
Dexamethasone (Decadron) 10 mg/m2/d po d1-14
Cyclophosphamide (Cytoxan) 1000 mg/m2 iv d29
6-Thioguanine 60 mg/m2/d po d29-42
Cytarabine (Ara-C) 75 mg/m2/d sc d29-32 and 36-39

Cycle 5 (16 months)
Vincristine 2 mg iv d1 qm
Prednisone 60 mg/m2/d d1-5 qm
Methotrexate (MTX) 20 mg/m2/d po d1, 8, 15, 22
6-Mercaptopurine (6-MP) 60 mg/m2/d po d1-28

Larson RA et al. A randomized controlled trial of filgramstim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic lymphoma: CALGB study 9111. Blood 1998; 92:1556 (link to the article).

Primary CNS lymphoma (back to top)

High dose Methotrexate
Methotrexate (MTX) 8 g/m2 iv over 4 hrs q2w till CR or up to 8 cycles, followed by 8 g/m2 iv qm x 11 months

Batchelor, T et al. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: A report of NABTT 96-07. J Clin Oncol 2003; 21:1044 (link to the article).

MPV + RT + Ara-C
Methotrexate (MTX) 3.5 g/m2 iv over 2 hours d1
Leucovorin 10 mg q6h x 12 doses starting 24 hours after MTX infusion
Vincristine 1.4 mg/m2 (max 2.8 mg) iv d1
Procarbazine 100 mg/m2 po qd d1-7 cycles 1, 3, 5 only
Q2w x 5 cycles
Intra-ommaya Methotrexate (MTX) 12 mg on alternate weeks after systemic MTX
Leucovorin 10 mg q6h x 8 doses starting 24 hours after intra-ommaya MTX
3-5 weeks after MPV, whole-brain radiotherapy (WBRT) 1.8 Gy/d x 25 days to a total of 45 Gy for patients younger than 60 years
3 weeks after WBRT, consolidation Cytarabine (Ara-C) 3 g/m2/d iv over 3 hours for 2 days. A second cycle of Cytarabine (Ara-C) is given 1 month later

Garvrilovic IT et al. Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol 2006; 24:4570 (link to the article).

Abrey LE et al. Treatment of primary CNS lymphoma: the next step. J Clin Oncol 2000; 18:3144 (link to the article).

R-MPV + RT + Ara-C
Rituximab (Rituxan) 500 mg/m2 iv over 5 hours d1 of each cycle
Methotrexate (MTX) 3.5 g/m2 iv over 2 hours d2 of each cycle
Leucovorin 20-25 mg q6h starting 24 hours after MTX infusion for 72 hours or until serum MTX level < 1 x 10^-8 mg/dL. Increase leucovorin to 40 mg q4h if MTX level > 1 x 10^-5 mg/dL at 48 hours or > 1 x 10^-8mg/dL at 72 hours
Vincristine 1.4 mg/m2 (max 2.8 mg) iv d2 of each cycle
Procarbazine 100 mg/m2 po qd d1-7 of odd-numbered cycles only
Filgrastim (Neupogen) 5 mcg/kg/d sc for 3 to 5 days starting 24 hours after the last dose of procarbazine during odd-numbered cycles, and starting 96 hours after MTX infusion or when MTX levels < 1 x 10^-8 mg/dL during even-numbered cycles
If positive CSF cytology: intra-ommaya Methotrexate (MTX) 12 mg between days 5 and 12 of each cycle
Q2w x 5 cycles
After 5 cycles of R-MPV:
If CR, whole-brain radiotherapy (WBRT) 1.8 Gy/d for 13 days to a total of 23.4 Gy beginning 3-5 weeks after the completion of R-MPV
If PR, 2 more additional cycles of R-MPV. If CR after 7 cycles of R-MPV, WBRT 1.8 Gy/d x 13 days to a total of 23.4 Gy beginning 3-5 weeks after the completion of R-MPV. If persistent disease after 7 cycles of R-MPV, WBRT 1.8 Gy/d x 25 days to a total of 45 Gy beginning 3-5 weeks after the completion of R-MPV
If stable disease or progressive disease after 5 cycles of R-MPV, WBRT 1.8 Gy/d x 25 days to a total of 45 Gy beginning 3-5 weeks after the completion of R-MPV
3 weeks after completion of WBRT, consolidation Cytarabine (Ara-C) 3 g/m2/d (max 6 g) iv over 3 hours for 2 days
Filgrastim (Neupogen) 5 mcg/kg/d sc for 10 days starting 48 hours after completion of Ara-C
A second cycle of Cytarabine (Ara-C) is given 1 month later

Shah GD et al. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol 2007; 25:4730 (link to the article).

Bonn protocol
Cycle A (3 wks)
Methotrexate (MTX) 5 g/m2 (3 g/m2 for patients over 65 years old) civi over 24 hrs d1
Vincristine 2 mg iv d1
Ifosfamide 800 mg/m2/d iv over 1 h d2-5
Dexamethasone (Decadron) 10 mg/m2/d po d2-5
Prednisone 2.5 mg intraventricularly qd d2-4
Methotrexate (MTX) 3 mg intraventricularly qd d2-4
Cytarabine (Ara-C) 30 mg intraventricularly d5

Cycle B (3 wks)
Methotrexate (MTX) 5 g/m2 (3 g/m2 for patients over 65 years old) civi over 24 hrs d1
Vincristine 2 mg iv d1
Cyclophosphamide (Cytoxan) 200 mg/m2/d iv over 1 h d2-5
Dexamethasone (Decadron) 10 mg/m2/d po d2-5
Prednisone 2.5 mg intraventricularly qd d2-4
Methotrexate (MTX) 3 mg intraventricularly qd d2-4
Cytarabine (Ara-C) 30 mg intraventricularly d5

Cycle C (3 wks)
Cytarabine (Ara-C) 3 g/m2/d iv over 3 hrs d1-2
Vindesine 5 mg iv d1
Dexamethasone (Decadron) 20 mg/m2/d po d3-7
Prednisone 2.5 mg intraventricularly qd d3-6
Methotrexate (MTX) 3 mg intraventricularly qd d3-6
Cytarabine (Ara-C) 30 mg intraventricularly d7

Sequence of cycles: A (d1-5), B (d22-26), C (d43-49). Repeat cycles A, B and C once for a total of 6 cycles.

Pels, H et al. Primary Central Nervous System Lymphoma: Results of a Pilot and Phase II Study of Systemic and Intraventricular Chemotherapy With Deferred Radiotherapy. J Clin Oncol 2003; 21:4489 (link to the article).

MTX + Ara-C + ASCT + RT
Methotrexate (MTX) 8 g/m2 iv over 4 hours d1, 10, 20
Leucovorine rescue 15 mg/m2 q6h until MTX clearance
Cytarabine (Ara-C) 3 g/m2 iv over 3 hours d 30 and 31
Thiotepa 40 mg/m2 iv d 31
Carmustine (BCNU) 400 mg/m2 iv d 50
Thiotepa 5 mg/kg iv d 51, 52
Autologous stem-cell transplantation (ASCT) d56
Hyperfractionated whole brain radiation 2 cycles of 1 Gy/d to 45 Gy for patients with CR or 50 Gy for patients with PR starting d90

Illerhaus G et al. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol 2006; 24:3865 (link to the article).

Temozolomide
Temozolomide (Temodar) 150 mg/m2/d po d1-5 q4w

Reni M et al. Temozolomide as salvage treatment in primary brain lymphomas. Br J Cancer 2007; 96:864 (link to the article).

CYVE + ASCT
Cytarabine (Ara-C) 2 g/m2/d iv over 3 hours d2-5 (if 60 years of age and older, reduce to 2 g/m2/d d2-4)
Cytarabine (Ara-C) 50 mg/m2/d iv over 12 hours d1-5
Etoposide (VP-16) 200 mg/m2/d iv over 2 hours d2-5 (if 60 years of age and older, reduce to 150 mg/m2/d d2-5)
Q4w x 2 cycles
Thiotepa 250 mg/m2/d iv d9-7
Busulfan (Myleran) total dose 10 mg/kg po or 8 mg/kg iv d6-4 (if 60 years of age and older, reduce dose by 40%)
Cyclophosphamide (Cytoxan) 60 mg/kg/d d3-2
Autologous stem cell transplantation (ASCT) on d0

Soussain C et al. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. J Clin Oncol 2008; 26:2512 (link to the article).

Soussain C et al. Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol 2001; 19:742 (link to the article).