Difference between revisions of "Classical Hodgkin lymphoma"
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# Engert A, Franklin J, Eich HT, Brillant C, Sehlen S, Cartoni C, Herrmann R, Pfreundschuh M, Sieber M, Tesch H, Franke A, Koch P, de Wit M, Paulus U, Hasenclever D, Loeffler M, Müller RP, Müller-Hermelink HK, Dühmke E, Diehl V. 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 Aug 10;25(23):3495-502. [http://jco.ascopubs.org/content/25/23/3495.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17606976 PubMed] | # Engert A, Franklin J, Eich HT, Brillant C, Sehlen S, Cartoni C, Herrmann R, Pfreundschuh M, Sieber M, Tesch H, Franke A, Koch P, de Wit M, Paulus U, Hasenclever D, Loeffler M, Müller RP, Müller-Hermelink HK, Dühmke E, Diehl V. 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 Aug 10;25(23):3495-502. [http://jco.ascopubs.org/content/25/23/3495.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17606976 PubMed] | ||
# Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM; Michelangelo Foundation; Gruppo Italiano di Terapie Innovative nei Linfomi; Intergruppo Italiano Linfomi. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21;365(3):203-12. [http://www.nejm.org/doi/full/10.1056/NEJMoa1100340#t=article link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21774708 PubMed] | # Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM; Michelangelo Foundation; Gruppo Italiano di Terapie Innovative nei Linfomi; Intergruppo Italiano Linfomi. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21;365(3):203-12. [http://www.nejm.org/doi/full/10.1056/NEJMoa1100340#t=article link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21774708 PubMed] | ||
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==B-AVD; AVD-A {{#subobject:b608e8|Regimen=1}}== | ==B-AVD; AVD-A {{#subobject:b608e8|Regimen=1}}== |
Revision as of 03:51, 24 March 2015
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Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.
81 regimens on this page
131 variants on this page
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Untreated, early-stage favorable
Definitions of favorable/unfavorable risk factors vary somewhat across sites; see original sources for details.
ABVD
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ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
Regimen #1
Study | Evidence | Comparator | Efficacy |
Raemaekers et al. 2014 (EORTC/LYSA/FIL H10) | Phase III | ABVD x 3 -> INRT | Inconclusive whether noninferior |
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on days 1 & 15
- Bleomycin (Blenoxane) 10 units/m2 IV once on days 1 & 15
- Vinblastine (Velban) 6 mg/m2 IV once on days 1 & 15
- Dacarbazine (DTIC) 375 mg/m2 IV once on days 1 & 15
4-week cycle x 2 cycles
Patients with a negative interim PET-CT (1 or 2 points on the 5-point Deauville scale) were randomized to receive 2 more cycles of ABVD versus 1 more cycle of ABVD followed by INRT 30 Gy (+ 6 Gy boost). Patients with a positive PET-CT proceeded to receive escalated BEACOPP followed by INRT 30 Gy (+ 6 Gy boost).
Regimen #2
Study | Evidence | Comparator | Efficacy |
Radford et al. 2012 (UK NCRI RAPID) | Phase III | ABVD x 3 -> IFRT | Inconclusive whether noninferior |
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on days 1 & 15
- Bleomycin (Blenoxane) 10 units/m2 IV once on days 1 & 15
- Vinblastine (Velban) 6 mg/m2 IV once on days 1 & 15
- Dacarbazine (DTIC) 375 mg/m2 IV once on days 1 & 15
4-week cycle x 3 cycles
Patients with a negative PET-CT after the 3rd cycle (1 or 2 points on the 5-point Deauville scale) were randomized to receive IFRT versus no further treatment. Patients with a positive PET-CT proceeded to receive one more cycle of ABVD followed by IFRT.
References
- Abstract: Radford, John, Barrington, Sally, Counsell, Nicholas, Pettengell, Ruth, Johnson, Peter, Wimperis, Jennie, Coltart, Stewart, Culligan, Dominic, Lister, Andrew, Bessell, Eric, Kruger, Anton, Popova, Bilyana, Hancock, Barry, Hoskin, Peter, Illidge, Timothy, O'Doherty, Michael. Involved Field Radiotherapy Versus No Further Treatment in Patients with Clinical Stages IA and IIA Hodgkin Lymphoma and a 'Negative' PET Scan After 3 Cycles ABVD. Results of the UK NCRI RAPID Trial. ASH Annual Meeting Abstracts 2012 120: 547 link to original abstract
- Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. link to original article contains protocol PubMed
ABVD -> XRT
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ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
Regimen #1
Study | Evidence | Comparator | Efficacy |
Raemaekers et al. 2014 (EORTC/LYSA/FIL H10) | Phase III | ABVD x 4 | Inconclusive whether noninferior |
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on days 1 & 15
- Bleomycin (Blenoxane) 10 units/m2 IV once on days 1 & 15
- Vinblastine (Velban) 6 mg/m2 IV once on days 1 & 15
- Dacarbazine (DTIC) 375 mg/m2 IV once on days 1 & 15
4-week cycle x 2 cycles
Patients with a negative interim PET-CT (1 or 2 points on the 5-point Deauville scale) were randomized to receive 2 more cycles of ABVD versus 1 more cycle of ABVD followed by INRT 30 Gy (+ 6 Gy boost). Patients with a positive PET-CT proceeded to receive escalated BEACOPP followed by INRT 30 Gy (+ 6 Gy boost).
Regimen #2
Study | Evidence | Comparator | Efficacy |
Radford et al. 2012 (UK NCRI RAPID) | Phase III | ABVD x 3 | Inconclusive whether noninferior |
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on days 1 & 15
- Bleomycin (Blenoxane) 10 units/m2 IV once on days 1 & 15
- Vinblastine (Velban) 6 mg/m2 IV once on days 1 & 15
- Dacarbazine (DTIC) 375 mg/m2 IV once on days 1 & 15
4-week cycle x 3 cycles
Patients with a negative PET-CT after the 3rd cycle (1 or 2 points on the 5-point Deauville scale) were randomized to receive IFRT versus no further treatment. Patients with a positive PET-CT proceeded to receive one more cycle of ABVD followed by IFRT.
References
- Abstract: Radford, John, Barrington, Sally, Counsell, Nicholas, Pettengell, Ruth, Johnson, Peter, Wimperis, Jennie, Coltart, Stewart, Culligan, Dominic, Lister, Andrew, Bessell, Eric, Kruger, Anton, Popova, Bilyana, Hancock, Barry, Hoskin, Peter, Illidge, Timothy, O'Doherty, Michael. Involved Field Radiotherapy Versus No Further Treatment in Patients with Clinical Stages IA and IIA Hodgkin Lymphoma and a 'Negative' PET Scan After 3 Cycles ABVD. Results of the UK NCRI RAPID Trial. ASH Annual Meeting Abstracts 2012 120: 547 link to original abstract
- Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. link to original article contains protocol PubMed
Untreated, early-stage unfavorable
Definitions of favorable/unfavorable risk factors vary somewhat across sites; see original sources for details.
ABVD
back to top |
ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
Regimen
Study | Evidence | Comparator | Efficacy |
Raemaekers et al. 2014 (EORTC/LYSA/FIL H10) | Phase III | ABVD x 4 -> INRT | Inconclusive whether noninferior |
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on days 1 & 15
- Bleomycin (Blenoxane) 10 units/m2 IV once on days 1 & 15
- Vinblastine (Velban) 6 mg/m2 IV once on days 1 & 15
- Dacarbazine (DTIC) 375 mg/m2 IV once on days 1 & 15
4-week cycle x 2 cycles
Patients with a negative interim PET-CT (1 or 2 points on the 5-point Deauville scale) were randomized to receive 4 more cycles of ABVD versus 2 more cycles of ABVD followed by INRT 30 Gy (+ 6 Gy boost). Patients with a positive PET-CT proceeded to receive escalated BEACOPP followed by INRT 30 Gy (+ 6 Gy boost).
References
- Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. link to original article contains protocol PubMed
ABVD -> XRT
back to top |
ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
Regimen
Study | Evidence | Comparator | Efficacy |
Raemaekers et al. 2014 (EORTC/LYSA/FIL H10) | Phase III | ABVD x 6 | Inconclusive whether noninferior |
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on days 1 & 15
- Bleomycin (Blenoxane) 10 units/m2 IV once on days 1 & 15
- Vinblastine (Velban) 6 mg/m2 IV once on days 1 & 15
- Dacarbazine (DTIC) 375 mg/m2 IV once on days 1 & 15
4-week cycle x 2 cycles
Patients with a negative interim PET-CT (1 or 2 points on the 5-point Deauville scale) were randomized to receive 4 more cycles of ABVD versus 2 more cycles of ABVD followed by INRT 30 Gy (+ 6 Gy boost). Patients with a positive PET-CT proceeded to receive escalated BEACOPP followed by INRT 30 Gy (+ 6 Gy boost).
References
- Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. link to original article contains protocol PubMed
Untreated, advanced stage
Generally defined as stage III/IV or stage II with bulky disease. Definitions for bulky disease vary across sites; see original sources for details,
ABVD
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ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
Regimen
Study | Evidence | Comparator | Efficacy |
Mounier et al. 2014 (LYSA H34) | Phase III | BEACOPP (escalated x 4, standard x 4) | Might have inferior EFS |
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on days 1 & 15
- Bleomycin (Blenoxane) 10 units/m2 IV once on days 1 & 15
- Vinblastine (Velban) 6 mg/m2 IV once on days 1 & 15
- Dacarbazine (DTIC) 375 mg/m2 IV once on days 1 & 15
4-week cycle x 8 cycles
References
- Mounier N, Brice P, Bologna S, Briere J, Gaillard I, Heczko M, Gabarre J, Casasnovas O, Jaubert J, Colin P, Delmer A, Devidas A, Bachy E, Nicolas-Virelizier E, Aoudjhane A, Humbrecht C, Andre M, Carde P; Lymphoma Study Association (LYSA). ABVD (8 cycles) versus BEACOPP (4 escalated cycles =4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Ann Oncol. 2014 Aug;25(8):1622-8. Epub 2014 May 14. link to original article contains verified protocol PubMed
ABVD, DD-DI
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ABVD, DD-DI: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine, Dose-Dense and Dose-Intense
Regimen
Study | Evidence |
Russo et al. 2014 | Phase II |
- Doxorubicin (Adriamycin) as follows:
- 35 mg/m2 IV once on days 1 & 11 for cycles 1 to 4
- 25 mg/m2 IV once on days 1 & 11 for cycles 5 & 6
- Bleomycin (Blenoxane) 10 units/m2 IV once on days 1 & 11
- Vinblastine (Velban) 6 mg/m2 IV once on days 1 & 11
- Dacarbazine (DTIC) 375 mg/m2 IV once on days 1 & 11
Supportive medications:
- Lenograstim (Granocyte) 263 µg SC once per day on days 6 to 8 and days 17 to 19 (6 doses per cycle)
21-day cycle x 6 cycles
References
- Russo F, Corazzelli G, Frigeri F, Capobianco G, Aloj L, Volzone F, De Chiara A, Bonelli A, Gatani T, Marcacci G, Donnarumma D, Becchimanzi C, de Lutio E, Ionna F, De Filippi R, Lastoria S, Pinto A. A phase II study of dose-dense and dose-intense ABVD (ABVD(DD-DI) ) without consolidation radiotherapy in patients with advanced Hodgkin lymphoma. Br J Haematol. 2014 Jul;166(1):118-29. Epub 2014 Mar 27. link to original article contains verified protocol PubMed
BEACOPP
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BEACOPP: Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone
Regimen
Study | Evidence | Comparator | Efficacy |
Diehl et al. 1998 (GHLSG HD9) | Phase III | Escalated dose BEACOPP | Inferior FFTF |
Diehl et al. 1998 (GHLSG HD9) | Phase III | COPP-ABVD | Seems to have superior FFTF |
Ballova et al. 2005 (GHLSG HD9elderly) | Phase III | COPP-ABVD | Seems not superior |
- Bleomycin (Blenoxane) 10 units/m2 IV once on day 8
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2mg per cycle) IV once on day 8
- Procarbazine (Matulane) 100 mg/m2 PO once per day on days 1 to 7
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 14
Q21days x 8 cycles
References
- Diehl V, Franklin J, Hasenclever D, Tesch H, Pfreundschuh M, Lathan B, Paulus U, Sieber M, Rueffer JU, Sextro M, Engert A, Wolf J, Hermann R, Holmer L, Stappert-Jahn U, Winnerlein-Trump E, Wulf G, Krause S, Glunz A, von Kalle K, Bischoff H, Haedicke C, Duehmke E, Georgii A, Loeffler M. BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 1998 Dec;16(12):3810-21. link to original articlecontains verified protocol PubMed
- Update: Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, Tesch H, Herrmann R, Dörken B, Müller-Hermelink HK, Dühmke E, Loeffler M; German Hodgkin's Lymphoma Study Group. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003 Jun 12;348(24):2386-95. link to original articlecontains protocol PubMed
- Ballova V, Rüffer JU, Haverkamp H, Pfistner B, Müller-Hermelink HK, Dühmke E, Worst P, Wilhelmy M, Naumann R, Hentrich M, Eich HT, Josting A, Löffler M, Diehl V, Engert A. A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly). Ann Oncol. 2005 Jan;16(1):124-31. link to original articlecontains protocol PubMed
BEACOPP, escalated dose
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BEACOPP: Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone
Regimen #1, Diehl et al. 1998; Diehl et al. 2003; Engert et al. 2009 (GHSG HD9); Borchmann et al. 2011 (GHSG HD12)
Phase III
- Bleomycin (Blenoxane) 10 units/m2 IV once on day 8
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days 1 to 3
- Doxorubicin (Adriamycin) 35 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2mg per cycle) IV once on day 8
- Procarbazine (Matulane) 100 mg/m2 PO once per day on days 1 to 7
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 14
3-week cycle x 8 cycles
Regimen #2, Viviani et al. 2011; Mounier et al. 2014 (LYSA H34)
Phase III
Escalated phase
- Bleomycin (Blenoxane) 10 units/m2 IV once on day 8
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days 1 to 3
- Doxorubicin (Adriamycin) 35 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 1250 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2mg per cycle) IV once on day 8
- Procarbazine (Matulane) 100 mg/m2 PO once per day on days 1 to 7
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 14
Supportive medications:
- Filgrastim (Neupogen) 300 mcg SC once per day starting day 8, continues until ANC > 1000/uL for 3 consecutive days (Viviani et al. 2011) or until day 14 (Mounier et al. 2014)
3-week cycle x 4 cycles
Standard phase
- Bleomycin (Blenoxane) 10 units/m2 IV once on day 8
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2mg per cycle) IV once on day 8
- Procarbazine (Matulane) 100 mg/m2 PO once per day on days 1 to 7
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 14
Supportive medications:
- Filgrastim (Neupogen) 300 mcg SC once per day starting day 8, continues until ANC > 1000/uL for 3 consecutive days (Viviani et al. 2011) or until day 14 (Mounier et al. 2014)
3-week cycle x 4 cycles
References
- Diehl V, Franklin J, Hasenclever D, Tesch H, Pfreundschuh M, Lathan B, Paulus U, Sieber M, Rueffer JU, Sextro M, Engert A, Wolf J, Hermann R, Holmer L, Stappert-Jahn U, Winnerlein-Trump E, Wulf G, Krause S, Glunz A, von Kalle K, Bischoff H, Haedicke C, Duehmke E, Georgii A, Loeffler M. BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 1998 Dec;16(12):3810-21. link to original articlecontains verified protocol PubMed
- Update: Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, Tesch H, Herrmann R, Dörken B, Müller-Hermelink HK, Dühmke E, Loeffler M; German Hodgkin's Lymphoma Study Group. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003 Jun 12;348(24):2386-95. link to original articlecontains protocol PubMed
- Update: Engert A, Diehl V, Franklin J, Lohri A, Dörken B, Ludwig WD, Koch P, Hänel M, Pfreundschuh M, Wilhelm M, Trümper L, Aulitzky WE, Bentz M, Rummel M, Sezer O, Müller-Hermelink HK, Hasenclever D, Löffler M. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol. 2009 Sep 20;27(27):4548-54. link to original article PubMed
- Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM; Michelangelo Foundation; Gruppo Italiano di Terapie Innovative nei Linfomi; Intergruppo Italiano Linfomi. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21;365(3):203-12. link to original article contains verified protocol PubMed
- Borchmann P, Haverkamp H, Diehl V, Cerny T, Markova J, Ho AD, Eich HT, Mueller-Hermelink HK, Kanz L, Greil R, Rank A, Paulus U, Smardova L, Huber C, Dörken B, Nerl C, Krause SW, Mueller RP, Fuchs M, Engert A. Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage hodgkin's lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group. J Clin Oncol. 2011 Nov 10;29(32):4234-42. Epub 2011 Oct 11. link to original article PubMed
- Mounier N, Brice P, Bologna S, Briere J, Gaillard I, Heczko M, Gabarre J, Casasnovas O, Jaubert J, Colin P, Delmer A, Devidas A, Bachy E, Nicolas-Virelizier E, Aoudjhane A, Humbrecht C, Andre M, Carde P; Lymphoma Study Association (LYSA). ABVD (8 cycles) versus BEACOPP (4 escalated cycles =4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Ann Oncol. 2014 Aug;25(8):1622-8. Epub 2014 May 14. link to original article contains verified protocol PubMed
C-MOPP/ABV
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C-MOPP: CyclophosphaMide, Oncovin (Vincristine), Procarbazine, Prednisone
ABV: Adriamycin (Doxorubicin), Bleomycin, Vinblastine
Regimen
Study | Evidence |
Montoto et al. 2000 | Phase II |
- Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum of 3 mg per dose) IV once on day 1
- Procarbazine (Matulane) 100 mg/m2 PO once per day on days 1 to 7
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 14
- Doxorubicin (Adriamycin) 35 mg/m2 IV once on day 8
- Bleomycin (Blenoxane) 10 mg/m2 IV once on day 8
- Vinblastine (Velban) 6 mg/m2 IV once on day 8
Q28days x 8 cycles
- 25 to 40 Gy of radiation therapy given over extended fields (mantle or inverted "Y" type) to patients with bulky disease or ones with residual disease after completion of chemotherapy
References
- Montoto S, Camós M, López-Guillermo A, Bosch F, Cervantes F, Blandé J, Esteve J, Cobo F, Nomdedeu B, Campo E, Montserrat E. Hybrid chemotherapy consisting of cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (C-MOPP/ABV) as first-line treatment for patients with advanced Hodgkin disease. Cancer. 2000 May 1;88(9):2142-8. link to original article contains protocol PubMed]
COPP-ABVD, C-MOPP/ABVD
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COPP: Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone
C-MOPP: CyclophosphaMide, Oncovin (Vincristine), Procarbazine, Prednisone
ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
Regimen
Phase III
COPP
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV drip days 1 & 8
- Vincristine (Oncovin) 1.4 mg/m2 (maximum of 2 mg per dose) IV once on days 1 & 8
- Procarbazine (Matulane) 100 mg/m2 (maximum of 150 mg per dose) PO once per day on days 1 to 14
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 3, 8 to 10
Q28days x 5 total cycles of C-MOPP, alternating with 5 total cycles of ABVD
ABVD
- Doxorubicin (Adriamycin) 25 mg/m2 IV drip days 1 & 15
- Bleomycin (Blenoxane) 9 mg/m2 (maximum of 15 mg per dose) IV drip days 1 & 15
- Vinblastine (Velban) 6 mg/m2 (maximum of 10 mg per dose) IV once on days 1 & 15
- Dacarbazine (DTIC) 250 mg/m2 IV drip days 1 & 15
Q28days x 5 total cycles of ABVD, alternating with 5 total cycles of C-MOPP
- 30 Gy of involved field radiation after completion of chemotherapy was given to patients with bulky (=10 cm maximum diameter) disease
Delayed treatment and discontinuations:
- Treatment was postponed for at least 1 week or until recovery if:
- Pretreatment ANC was <1500
- Platelet count was <100 x 10^3
- AST/S-GOT was >100 IU/L
- Total bilirubin was >2
- Vincristine (Oncovin) and Vinblastine (Velban) were temporarily discontinued if patients had grade 2 or greater neurotoxicity (e.g. motor weakness, paresthesia, constipation)
- Doxorubicin (Adriamycin) was discontinued if cardiac LV ejection fraction was <50%
- Bleomycin (Blenoxane) was stopped if the PaO2 was less than 70 mmHg or if it decreased more than 10 mmHg from the previous measurement
- Note: Dacarbazine (DTIC) 250 mg/m2 was used at this dose reduction based on experiences in a pilot study in which there was severe emesis with Dacarbazine (DTIC) 375 mg/m2.
References
- Diehl V, Franklin J, Hasenclever D, Tesch H, Pfreundschuh M, Lathan B, Paulus U, Sieber M, Rueffer JU, Sextro M, Engert A, Wolf J, Hermann R, Holmer L, Stappert-Jahn U, Winnerlein-Trump E, Wulf G, Krause S, Glunz A, von Kalle K, Bischoff H, Haedicke C, Duehmke E, Georgii A, Loeffler M. BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 1998 Dec;16(12):3810-21. link to original articlecontains verified protocol PubMed
- Update: Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, Tesch H, Herrmann R, Dörken B, Müller-Hermelink HK, Dühmke E, Loeffler M; German Hodgkin's Lymphoma Study Group. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003 Jun 12;348(24):2386-95. link to original articlecontains protocol PubMed
- Takenaka T, Mikuni C, Miura A, Sasaki T, Suzuki H, Hotta T, Hirano M, Fukuhara S, Sugiyama H, Nasu K, Dohi H, Kozuru M, Tomonaga M, Tajima K, Niimi M, Fukuda H, Mukai K, Shimoyama M. Alternating combination chemotherapy C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) in clinical stage II-IV Hodgkin's disease: a multicenter phase II study (JCOG 8905). The Lymphoma Study Group of the Japan Clinical Oncology Group. Jpn J Clin Oncol. 2000 Mar;30(3):146-52. link to original article contains protocol PubMed
- Ballova V, Rüffer JU, Haverkamp H, Pfistner B, Müller-Hermelink HK, Dühmke E, Worst P, Wilhelmy M, Naumann R, Hentrich M, Eich HT, Josting A, Löffler M, Diehl V, Engert A. A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly). Ann Oncol. 2005 Jan;16(1):124-31. link to original articlecontains protocol PubMed
MOPP
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MOPP: Mustargen (Mechlorethamine), Oncovin (Vincristine), Procarbazine, Prednisone
Regimen
Phase III
- Mechlorethamine (Mustargen) 6 mg/m2 IV once on days 1 & 8
- Vincristine (Oncovin) 1.4 mg/m2 (sometimes each individual dose is capped at 2 mg) IV once on days 1 & 8
- Procarbazine (Matulane) 100 mg/m2 PO once per day days 1 to 14
- Prednisone (Sterapred) 40 mg/m2 PO once per day days 1 to 14
Q28days x 6 cycles
References
- Devita VT Jr, Serpick AA, Carbone PP. Combination chemotherapy in the treatment of advanced Hodgkin's disease. Ann Intern Med. 1970 Dec;73(6):881-95. link to original article contains protocol PubMed content property of HemOnc.org
- Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 1992 Nov 19;327(21):1478-84. link to original article PubMed
Stanford V
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Regimen
Phase III
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on days 1 & 15
- Vinblastine (Velban) 6 mg/m2 IV once on days 1 & 15
- Mechlorethamine (Mustargen) 6 mg/m2 IV once on day 1
- Etoposide (Vepesid) 60 mg/m2 IV once on days 15 & 16
- Vincristine (Oncovin) 1.4 mg/m2 (maximum of 2mg in any individual dose) IV once on days 8 & 22
- Bleomycin (Blenoxane) 5 units/m2 IV once on days 8 & 22
- Prednisone (Sterapred) 40 mg/m2 PO every other day (see note below about taper)
Supportive medications:
- If dose reduction or delay occurred at any time during chemotherapy, Filgrastim (Neupogen) 5 mcg/kg SC per day x 5 days (starting 48 hours after myelosuppressive chemotherapy) should be given after all subsequent day 1 and 15 doses of chemotherapy. It was not precisely specified when to discontinue Filgrastim (Neupogen).
- Ranitidine (Zantac) 150 mg PO BID throughout the course of treatment
- Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID throughout the course of treatment
- Acyclovir (Zovirax) 200 mg PO TID throughout the course of treatment
- Ketoconazole (Nizoral) 200 mg PO once per day throughout the course of treatment; note: this may be optional--Horning SJ et al. J Clin Oncol (2000) listed this as a prophylactic medication, but Horning SJ et al. J Clin Oncol (2002) did not list this when prophylactic medications were specifically listed.
Q28days x 3 cycles
- 36 Gy of consolidative radiation (1.8 Gy in 20 fractions) is started 2 to 4 weeks after chemotherapy is complete and is given to sites of disease = 5 cm and/or to macroscopic nodules in the spleen.
- Taper Prednisone (Sterapred) by "10 mg every other day between weeks 10 and 12":
- On week 10, Prednisone (Sterapred) 30 mg/m2 PO every other day.
- On week 11, Prednisone (Sterapred) 20 mg/m2 PO every other day.
- On week 12, Prednisone (Sterapred) 10 mg/m2 PO every other day, then off.
- Note: In patients =50 years old:
- Reduce doses of Vincristine (Oncovin) during cycle 3 to 1 mg.
- Reduce doses of Vinblastine (Velban) during cycle 3 to 4 mg/m2.
Dose reductions and delayed treatment:
- Doses of Doxorubicin (Adriamycin), Vinblastine (Velban), Mechlorethamine (Mustargen), and Etoposide (Vepesid) were reduced to 65% of the original dose if the ANC on the day of treatment was 500 to 1000. If ANC was <500 the day of treatment, therapy was delayed for 1 week, and therapy resumed the following week at the dose indicated by the ANC. As noted above, Filgrastim (Neupogen) was incorporated into all subsequent treatments if there were any dose reductions or delays.
References
- Horning SJ, Williams J, Bartlett NL, Bennett JM, Hoppe RT, Neuberg D, Cassileth P. Assessment of the Stanford V regimen and consolidative radiotherapy for bulky and advanced Hodgkin's disease: Eastern Cooperative Oncology Group pilot study E1492. J Clin Oncol. 2000 Mar;18(5):972-80. link to original article contains protocol PubMed
- Horning SJ, Hoppe RT, Breslin S, Bartlett NL, Brown BW, Rosenberg SA. Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: mature results of a prospective clinical trial. J Clin Oncol. 2002 Feb 1;20(3):630-7. link to original article contains protocol PubMed
- Edwards-Bennett SM, Jacks LM, Moskowitz CH, Wu EJ, Zhang Z, Noy A, Portlock CS, Straus DJ, Zelenetz AD, Yahalom J. Stanford V program for locally extensive and advanced Hodgkin lymphoma: the Memorial Sloan-Kettering Cancer Center experience. Ann Oncol. 2010 Mar;21(3):574-81. link to original article PubMed
- Gordon LI, Hong F, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, Wagner H, Stiff PJ, Cheson BD, Gospodarowicz M, Advani R, Kahl BS, Friedberg JW, Blum KA, Habermann TM, Tuscano JM, Hoppe RT, Horning SJ. Randomized Phase III Trial of ABVD Versus Stanford V With or Without Radiation Therapy in Locally Extensive and Advanced-Stage Hodgkin Lymphoma: An Intergroup Study Coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013 Feb 20;31(6):684-91. Epub 2012 Nov 26. link to original article PubMed
Untreated
ABVD
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ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
Regimen #1
Phase III
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on days 1 & 15
- Bleomycin (Blenoxane) 10 units/m2 IV once on days 1 & 15 (1 unit test dose with cycle 1 doses, 60 minutes prior to remainder of full dose)
- Vinblastine (Velban) 6 mg/m2 IV once on days 1 & 15
- Dacarbazine (DTIC) 375 mg/m2 IV once on days 1 & 15
4-week cycle x 4 to 6 cycles based on stage, response, and whether radiation therapy is used.
References
- Bonadonna G, Santoro A. ABVD chemotherapy in the treatment of Hodgkin's disease. Cancer Treat Rev. 1982 Mar;9(1):21-35. (no link to original article available) PubMed
- Bonadonna G. Chemotherapy strategies to improve the control of Hodgkin's disease: the Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res. 1982 Nov;42(11):4309-20. link to original article contains protocol PubMed
- Santoro A, Bonadonna G, Valagussa P, Zucali R, Viviani S, Villani F, Pagnoni AM, Bonfante V, Musumeci R, Crippa F et al. Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy. J Clin Oncol. 1987 Jan;5(1):27-37. link to original article PubMed
- Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 1992 Nov 19;327(21):1478-84. link to original article PubMed
- Carde P, Hagenbeek A, Hayat M, Monconduit M, Thomas J, Burgers MJ, Noordijk EM, Tanguy A, Meerwaldt JH, Le Fur R 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 Nov;11(11):2258-72. link to original article PubMed
- Bonadonna G, Bonfante V, Viviani S, Di Russo A, Villani F, Valagussa P. ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin's disease: long-term results. J Clin Oncol. 2004 Jul 15;22(14):2835-41. link to original article contains protocol PubMed
- Engert A, Franklin J, Eich HT, Brillant C, Sehlen S, Cartoni C, Herrmann R, Pfreundschuh M, Sieber M, Tesch H, Franke A, Koch P, de Wit M, Paulus U, Hasenclever D, Loeffler M, Müller RP, Müller-Hermelink HK, Dühmke E, Diehl V. 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 Aug 10;25(23):3495-502. link to original article contains protocol PubMed
- Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM; Michelangelo Foundation; Gruppo Italiano di Terapie Innovative nei Linfomi; Intergruppo Italiano Linfomi. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21;365(3):203-12. link to original article contains verified protocol PubMed
B-AVD; AVD-A
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B-AVD: Brentuximab vedotin, Adriamycin, Vinblastine, Dacarbazine
AVD-A: Adriamycin, Vinblastine, Dacarbazine, Adcetris (brentuximab vedotin),
Regimen
Non-randomized
This was a phase I trial but had >20 patients in the MTD expansion cohort; a phase III trial is underway.
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on days 1 & 15
- Vinblastine (Velban) 6 mg/m2 IV once on days 1 & 15
- Dacarbazine (DTIC) 375 mg/m2 IV once on days 1 & 15
- Brentuximab vedotin (Adcetris) 1.2 mg/kg IV once on days 1 & 15, within "about" 1 hour of AVD infusion completion
4-weeks cycle x up to 6 cycles
"Consolidative radiotherapy was permitted at the investigator's discretion."
References
- Younes A, Connors JM, Park SI, Fanale M, O'Meara MM, Hunder NN, Huebner D, Ansell SM. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol. 2013 Dec;14(13):1348-56. Epub 2013 Nov 15. link to original article contains verified protocol PubMed
- Update: Abstract: Joseph M Connors, MD, Stephen Ansell, Steven I. Park, MD, Michelle A. Fanale, M.D. and Anas Younes. Brentuximab Vedotin Combined with ABVD or AVD for Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma: Long Term Outcomes. ASH Annual Meeting 2014, Abstract 292 link to abstract
Brentuximab vedotin (Adcetris)
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Regimen, Yasenchak et al. 2013
Phase II
- Brentuximab vedotin (Adcetris) 1.8 mg/kg IV over 30 minutes on day 1
21-day cycle up to 16 cycles
References
- Abstract: Christopher A. Yasenchak, MD, Robert Chen, MD, Jeff P. Sharman, MD, Ralph V. Boccia, MD, Beata Holkova, MD, Peter J. Rosen, MD, Jonathan W. Friedberg, MD, Megan M. O'Meara, MD and Andres Forero-Torres, MD. A Phase 2 Study Of Single-Agent Brentuximab Vedotin For Front-Line Therapy Of Hodgkin Lymphoma In Patients Age 60 Years and Above: Interim Results. ASH 2013 Abstract 4389 link to abstract
- Update: Abstract: Andres Forero-Torres, MD, Beata Holkova, MD, Jeff P. Sharman, MD, Jonathan W. Friedberg, MD, Maurice J. Berkowitz, MD, William Fintel, MD, Robert Chen, MD, Ralph V. Boccia, MD, Mansoor Saleh, MD, Neil Josephson, MD, Maria Corinna Palanca-Wessels, MD, PhD and Christopher A. Yasenchak, MD. Brentuximab Vedotin Monotherapy and in Combination with Dacarbazine in Frontline Treatment of Hodgkin Lymphoma in Patients Aged 60 Years and Above: Interim Results of a Phase 2 Study. ASH 2014 Abstract 294 link to abstract
BV-ABVD
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BV-ABVD: Brentuximab Vedotin, Adriamycin, Bleomycin, Vinblastine, Dacarbazine
Regimen, Federico et al. 2014
Phase II, <20 patients reported
Brentuximab vedotin portion
- Brentuximab vedotin (Adcetris) 1.8 mg/kg IV over 30 minutes
3-week cycle x 2 cycles, followed by:
ABVD portion
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on days 1 & 15
- Bleomycin (Blenoxane) 10 units/m2 IV once on days 1 & 15 (1 unit test dose with cycle 1 doses, 60 minutes prior to remainder of full dose)
- Vinblastine (Velban) 6 mg/m2 IV once on days 1 & 15
- Dacarbazine (DTIC) 375 mg/m2 IV once on days 1 & 15
4-week cycle x 3 to 6 cycles based on stage, +/- radiation therapy
References
- Abstract: Massimo Federico, Emanuela Anna Pesce, Francesco Merli, Stefano Luminari, Stephane Chauvie, Cinzia Pellegrini, Luigi Marcheselli, Isabella Capodanno, Fiorella Ilariucci, Massimiliano Salati, Lisa Argnani, Pier Luigi Zinzani. A pilot phase II study with brentuximab vedotin followed by ABVD in patients with previously untreated Hodgkin lymphoma: A preliminary report. J Clin Oncol 32:5s, 2014 (suppl; abstr 8507) link to original abstract
ChIVPP
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ChIVPP: ChlorambucIl, Vinblastine, Procarbazine, Prednisone
Regimen
Phase II
- Chlorambucil (Leukeran) 6 mg/m2 (maximum 10 mg/day) PO once per day on days 1 to 14
- Vinblastine (Velban) 6 mg/m2 (maximum 10 mg/dose) IV once on days 1 & 8
- Procarbazine (Matulane) 100 mg/m2 (maximum 150 mg/day) PO once per day on days 1 to 14
- Prednisone (Sterapred) 40 mg PO once per day on days 1 to 14
Q28days to complete remission plus 2 cycles; minimum of 6 cycles and maximum of 8 cycles
References
- The International ChlVPP Treatment Group. ChlVPP therapy for Hodgkin's disease: experience of 960 patients. Ann Oncol. 1995 Feb;6(2):167-72. link to original article contains protocol PubMed
RABVD
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RABVD: Rituximab, Adriamycin, Bleomycin, Vinblastine, Dacarbazine
Regimen #1, Younes et al. 2012
Phase II
- Rituximab (Rituxan) 375 mg/m2 IV once per week x 6 weeks
- Doxorubicin (Adriamycin) 25 mg/m2 IV once per day on days 1 & 15
- Bleomycin (Blenoxane) 10 units/m2 IV once per day on days 1 & 15
- Vinblastine (Velban) 6 mg/m2 IV once per day on days 1 & 15
- Dacarbazine (DTIC) 375 mg/m2 IV once per day on days 1 & 15
Q28days x 6 cycles (except rituximab, which is given for a total of 6 doses)
Regimen #2, Kasamon et al. 2012
Phase II
- Rituximab (Rituxan) 375 mg/m2 IV once per day 1) one week prior to cycle 1 of ABVD; 2) on days 1, 8, 15, 22 of cycle 1; 3) on day 1 of cycles 2, 4, and 6
- Doxorubicin (Adriamycin) 25 mg/m2 IV once per day on days 1 & 15
- Bleomycin (Blenoxane) 10 units/m2 IV once per day on days 1 & 15
- Vinblastine (Velban) 6 mg/m2 IV once per day on days 1 & 15
- Dacarbazine (DTIC) 375 mg/m2 IV once per day on days 1 & 15
Q28days x 6 to 8 cycles
References
- Younes A, Oki Y, McLaughlin P, Copeland AR, Goy A, Pro B, Feng L, Yuan Y, Chuang HH, Macapinlac HA, Hagemeister F, Romaguera J, Samaniego F, Fanale MA, Dabaja BS, Rodriguez MA, Dang N, Kwak LW, Neelapu SS, Fayad LE. Phase 2 study of rituximab plus ABVD in patients with newly diagnosed classical Hodgkin lymphoma. Blood. 2012 May 3;119(18):4123-8. Epub 2012 Feb 27. link to original article contains protocol PubMed
- Kasamon YL, Jacene HA, Gocke CD, Swinnen LJ, Gladstone DE, Perkins B, Link BK, Popplewell LL, Habermann TM, Herman JM, Matsui WH, Jones RJ, Ambinder RF. Phase 2 study of rituximab-ABVD in classical Hodgkin lymphoma. Blood. 2012 May 3;119(18):4129-32. Epub 2012 Feb 16. link to original article contains partial protocol PubMed
Relapsed/refractory
Bendamustine (Treanda)
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Regimen
Phase II
- Bendamustine (Treanda) 120 mg/m2 IV over 30 minutes on days 1 & 2
Supportive medications:
- Filgrastim (Neupogen) or Pegfilgrastim (Neulasta) used each cycle; paper does not specify exact timing/duration
- PCP prophylaxis and antiemetics according to institutional guidelines
28-day cycles x up to 6 cycles
References
- Moskowitz AJ, Hamlin PA Jr, Perales MA, Gerecitano J, Horwitz SM, Matasar MJ, Noy A, Palomba ML, Portlock CS, Straus DJ, Graustein T, Zelenetz AD, Moskowitz CH. Phase II Study of Bendamustine in Relapsed and Refractory Hodgkin Lymphoma. J Clin Oncol. 2013 Feb 1;31(4):456-60. Epub 2012 Dec 17. link to original article contains verified protocol PubMed
- Retrospective: Anastasia A, Carlo-Stella C, Corradini P, Salvi F, Rusconi C, Pulsoni A, Hohaus S, Pregno P, Viviani S, Brusamolino E, Luminari S, Giordano L, Santoro A. Bendamustine for Hodgkin lymphoma patients failing autologous or autologous and allogeneic stem cell transplantation: a retrospective study of the Fondazione Italiana Linfomi. Br J Haematol. 2014 Mar 7. [Epub ahead of print] link to original article PubMed
Brentuximab vedotin (Adcetris)
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Regimen #1, Rothe et al. 2012; Gopal et al. 2012; Younes et al. 2012
Phase II
- Brentuximab vedotin (Adcetris) 1.8 mg/kg IV over 30 minutes on day 1
Supportive medications:
- Rothe et al. 2012: "no premedications were administered"
21-day cycles, given until progression (Rothe et al. 2012; Gopal et al. 2012) or up to 16 infusions (Younes et al. 2012)
Regimen #2, Schoder et al. 2013
Phase II
- Brentuximab vedotin (Adcetris) 1.2 mg/kg IV once per week on weeks 1 to 3 (3 doses per cycle)
4-week cycle x 2 cycles
Optimal responders (normalization of PET) proceeded to autologous stem cell transplant with BEAM, CBV, or high dose chemoradiotherapy. Suboptimal responders proceeded to receive two cycles of augmented ICE (not described in abstract) prior to transplant.
References
- Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, Forero-Torres A, Moskowitz CH, Connors JM, Engert A, Larsen EK, Kennedy DA, Sievers EL, Chen R. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol. 2012 Jun 20;30(18):2183-9. Epub 2012 Mar 26. link to original article contains verified protocol PubMed
- Update: Abstract: Robert Chen, Scott E. Smith, Stephen M Ansell, Joseph D Rosenblatt, Kerry J. Savage, Joseph M. Connors, Andreas Engert, Emily K. Larsen, Dirk Huebner, Eric L. Sievers, Anas Younes. Three-Year Follow-Up Data and Characterization Of Long-Term Remissions From An Ongoing Phase 2 Study Of Brentuximab Vedotin In Patients With Relapsed Or Refractory Hodgkin Lymphoma. Blood Nov 2013,122(21)4382. link to abstract
- Update: Abstract: The 12th International Conference on Malignant Lymphoma, Lugano, Switzerland, June 19-20, 2013
- Update: Gopal AK, Chen R, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Connors JM, Engert A, Larsen EK, Chi X, Sievers EL, Younes A. Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Blood. 2014 Dec 22. [Epub ahead of print] link to original article PubMed
- Gopal AK, Ramchandren R, O'Connor OA, Berryman RB, Advani RH, Chen R, Smith SE, Cooper M, Rothe A, Matous JV, Grove LE, Zain J. Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation. Blood. 2012 Jul 19;120(3):560-8. Epub 2012 Apr 17. link to original article contains verified protocol PubMed
- Rothe A, Sasse S, Goergen H, Eichenauer DA, Lohri A, Jäger U, Bangard C, Böll B, von Bergwelt Baildon M, Theurich S, Borchmann P, Engert A. Brentuximab vedotin for relapsed or refractory CD30+ hematologic malignancies: the German Hodgkin Study Group experience. Blood. 2012 Aug 16;120(7):1470-2. Epub 2012 Jul 11. link to original article contains verified protocol PubMed
- Gibb A, Jones C, Bloor A, Kulkarni S, Illidge T, Linton K, Radford J. Brentuximab vedotin in refractory CD30+ lymphomas: a bridge to allogeneic transplantation in approximately one quarter of patients treated on a Named Patient Programme at a single UK center. Haematologica. 2013 Apr;98(4):611-4. Epub 2012 Oct 12. link to original article contains verified protocol PubMed
- Abstract: Heiko Schoder, John F. Gerecitano, Paul Hamlin, Steven M. Horwitz, Matthew J Matasar, Vahakn S Keskinyan, Susan McCall, Ariela Noy, M. Lia Palomba, Carol S. Portlock, David J Straus, Joachim Yahalom, Anas Younes, Andrew D Zelenetz, Craig H. Moskowitz. FDG-PET Adapted Sequential Therapy With Brentuximab Vedotin and Augmented ICE Followed By Autologous Stem Cell Transplant For Relapsed and Refractory Hodgkin Lymphoma. Blood Nov 2013,122(21)2099 link to abstract
DHAP
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DHAP: Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)
Regimen
Study | Evidence | ||
Valesquez et al. 1988 | Phase II | ||
Sureda et al. 2011 | Phase II |
- Dexamethasone 40 mg PO/IV over 15 minutes once per day on days 1 to 4
- Cytarabine (Cytosar) 2000 mg/m2 IV given over 3 hours Q12H x 2 doses on day 2
- Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1
Supportive medications:
- Normal saline with mannitol 50 g/L given at 250 mL/H x 36 hours, starting 6 hours before Cisplatin (Platinol) infusion was started
21 to 28-day cycles (depending on degree of myelosuppression)
Velasquez et al. 1988 gave 6 to 10 cycles, with therapy given 4 cycles beyond the maximum antitumor effect. Sureda et al. 2011 gave 2 cycles, with responders proceeding to RIC allogeneic stem cell transplant.
- Aside from the table below (from Velasquez et al. 1988), there were no specific cutoff criteria about dose modifications or delays of treatment.
Dose modifications:
- Patients >70 years old received Cytarabine (Cytosar) dose reduced to 1000 mg/m2
Dose modifications | ||
---|---|---|
Event | Cytarabine (Cytosar) | Cisplatin (Platinol) |
ANC <200 | 1000 mg/m2 x 2 doses | 100 mg/m2 |
Platelets <20 x 10^3 | 1000 mg/m2 x 2 doses | 100 mg/m2 |
Sepsis associated with neutropenia | 500 mg/m2 x 1 dose | 100 mg/m2 |
Cr 1.5 to 2.0 | - | 75 mg/m2 |
Cr 2.1-3.0 | - | 50 mg/m2 |
References
- Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, Barlogie B. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117-22. link to original article contains protocol PubMed
- Sureda A, Canals C, Arranz R, Caballero D, Ribera JM, Brune M, Passweg J, Martino R, Valcárcel D, Besalduch J, Duarte R, León A, Pascual MJ, García-Noblejas A, López Corral L, Xicoy B, Sierra J, Schmitz N. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin's lymphoma. Results of the HDR-ALLO study - a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2012 Feb;97(2):310-7. Epub 2011 Oct 11. link to original article contains protocol PubMed
DHAP - time intensified
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DHAP: Dexamethasone, High-dose Ara-C, Platinol
Regimen
Phase II
This was used as a salvage regimen for relapsed/refractory Hodgkin Lymphoma in patients who were planned for high-dose chemotherapy (HDCT) and autologous stem cell transplantation.
- Dexamethasone 40 mg IV once per day on days 1 to 4
- Cytarabine (Cytosar) 2000 mg/m2 IV given over 3 hours Q12H x 2 doses on day 2
- Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1
Supportive medications:
- Hydration at 250 mL/H started 2 to 6 hours before Cisplatin (Platinol) infusion was started
- Prednisolone acetate 1% eyedrops 1 drop to both eyes TID; start 12 hours before start of Cytarabine (Cytosar) and continued for 2 days after cytarabine administration complete
- Ondansetron (Zofran) 8 mg IV once on days 1 & 2
- Filgrastim (Neupogen) 5 mcg/kg SQ per day, start 24 hours after last dose of Cytarabine (Cytosar) and continue until ANC >2,500 for 3 days
Variable number of days between cycles depending on count recovery x 2 cycles Median time between cycle 1 and 2 was 16 days. The paper did not definitively specify what criteria needed to be fulfilled before cycle 2 was given. Baseline eligibility criteria for the study included WBC >3.5 x 10^3, Hb =8, platelets =100 x 10^3.
References
- Josting A, Rudolph C, Reiser M, Mapara M, Sieber M, Kirchner HH, Dörken B, Hossfeld DK, Diehl V, Engert A; Participating Centers. Time-intensified dexamethasone/cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin's disease. Ann Oncol. 2002 Oct;13(10):1628-35. link to original article contains protocol PubMed
ESHAP
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ESHAP: Etoposide, Solumedrol, High-dose Ara-C, Platinum
Regimen
- Etoposide (Vepesid) 40 mg/m2 IV once per day on days 1 to 4, infuse over 1 hour
- Methylprednisolone (Solumedrol) 500 mg IV once per day on days 1 to 5, infuse over 15 to 30 minutes
- Cytarabine (Cytosar) 2000 mg/m2 IV once on day 5, infuse over 2 hours
- Cisplatin (Platinol) 25 mg/m2/day (total dose: 100 mg/m2) IV once per day on days 1 to 4, continuous infusion over 24 hours
Supportive medications:
- Prednisolone acetate 1% eyedrops 1 drop to both eyes TID; start 15 minutes before Cytarabine (Cytosar) and continue until 48 hours after Cytarabine (Cytosar) is completed.
Q21 to 28 days x 6 to 8 cycles in responding patients
References
- Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. link to original articlePubMed
Everolimus (Afinitor)
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Regimen, Johnston et al. 2010
Phase II
- Everolimus (Afinitor) 10 mg PO once per day on an empty stomach
Supportive medications:
- "Patients could receive white blood cell growth factors if neutropenia developed. Erythropoietin treatment for anemia was permitted."
28-day cycles, given until progression or unacceptable toxicity
References
- Johnston PB, Inwards DJ, Colgan JP, Laplant BR, Kabat BF, Habermann TM, Micallef IN, Porrata LF, Ansell SM, Reeder CB, Roy V, Witzig TE. A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma. Am J Hematol. 2010 May;85(5):320-4. link to original article contains verified protocol PubMed
GCD +/- R
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GCD +/- R: Gemcitabine, Carboplatin, Dexamethasone, Rituximab
Regimen
Phase II
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once on days 1 & 8
- Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1
- Dexamethasone 40 mg PO once per day on days 1 to 4
- If disease is CD20 positive: Rituximab (Rituxan) 375 mg/m2 slow IV infusion once on day 8
Supportive medications:
- Growth factor support and antibiotic prophylaxis used is at the discretion of the treating physician.
Q21days x up to 4 cycles
Dose modifications:
- If on day 8, platelets are 50 to 100 or ANC 500 to 1000: reduce Gemcitabine (Gemzar) dose by 25% for that dose only.
- If on day 8, platelets are <50 or ANC <500: No day 8 Gemcitabine (Gemzar) dose given.
- Subsequent cycles would be given at full dose if patients had platelets =50 or ANC =1000.
- If counts were not adequate, the next cycle can be delayed for up to 3 weeks until counts are adequate for treatment.
References
- Gopal AK, Press OW, Shustov AR, Petersdorf SH, Gooley TA, Daniels JT, Garrison MA, Gjerset GF, Lonergan M, Murphy AE, Smith JC, Pagel JM. Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium. Leuk Lymphoma. 2010 Aug;51(8):1523-9. link to original article contains protocol PubMed
GVD
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GVD: Gemcitabine, Vinorelbine, Doxil
Regimen, Bartlett et al. 2007 (CALGB 59804)
Phase II
Transplant-naive patients
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once on days 1 & 8 second medication given
- Vinorelbine (Navelbine) 20 mg/m2 IV over 6 to 10 minutes once on days 1 & 8 first medication given
- Doxorubicin liposomal (Doxil) 15 mg/m2 IV over 30 to 60 minutes once on days 1 & 8 third medication given
Q21days x 2 to 6 cycles
Post-transplant patients
- Gemcitabine (Gemzar) 800 mg/m2 IV over 30 minutes once on days 1 & 8 second medication given
- Vinorelbine (Navelbine) 15 mg/m2 IV over 6 to 10 minutes once on days 1 & 8 first medication given
- Doxorubicin liposomal (Doxil) 10 mg/m2 IV over 30 to 60 minutes once on days 1 & 8 third medication given
Q21days x 2 to 6 cycles
Dose levels: Note: These dose levels are listed primarily for historical purposes and were used in the trial while dose levels and dose limiting toxicities (DLT) and maximum tolerated dose (MTD) were being determined. The MTD dosages used above correspond to dose level 1 for transplant-naive patients and dose level -1 for post-transplant patients.
- Dose level 1:
- Vinorelbine (Navelbine) 20 mg/m2 IV over 6 to 10 minutes once on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once on days 1 & 8
- Doxorubicin liposomal (Doxil) 15 mg/m2 IV over 30 to 60 minutes once on days 1 & 8
- Dose level 2:
- Vinorelbine (Navelbine) 20 mg/m2 IV over 6 to 10 minutes once on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once on days 1 & 8
- Doxorubicin liposomal (Doxil) 20 mg/m2 IV over 30 to 60 minutes once on days 1 & 8
- Dose level -1:
- Vinorelbine (Navelbine) 15 mg/m2 IV over 6 to 10 minutes once on days 1 & 8
- Gemcitabine (Gemzar) 800 mg/m2 IV over 30 minutes once on days 1 & 8
- Doxorubicin liposomal (Doxil) 10 mg/m2 IV over 30 to 60 minutes once on days 1 & 8
Dose modifications:
- If febrile neutropenia occurs: Decrease treatment by one dose level.
- If febrile neutropenia occurs on dose level -1: treating physician can choose to either:
- Use Filgrastim (Neupogen) or Sargramostim (Leukine).
- Reduce dose of Gemcitabine (Gemzar) and Vinorelbine (Navelbine) by 25% for all subsequent cycles.
- If febrile neutropenia reoccurred despite dose reduction patient were discontinued from this protocol.
- If on day 8, platelets are 50 to 100 or ANC 500 to 1000: reduce Gemcitabine (Gemzar) dose by 25% for that dose only.
- If on day 8, platelets are <50 or ANC <500: No day 8 Gemcitabine (Gemzar) dose given.
- Subsequent cycles would be given at full dose if patients had platelets =50 or ANC =1000.
- If counts were not adequate, the next cycle can be delayed for up to 3 weeks until counts are adequate for treatment.
References
- Bartlett NL, Niedzwiecki D, Johnson JL, Friedberg JW, Johnson KB, van Besien K, Zelenetz AD, Cheson BD, Canellos GP; Cancer Leukemia Group B. Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin's lymphoma: CALGB 59804. Ann Oncol. 2007 Jun;18(6):1071-9. link to original article contains protocol PubMed
GVP
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GVP: Gemcitabine, Vinorelbine, Prednisolone
Regimen
Phase II
- Gemcitabine (Gemzar) 1000 mg/m2 IV once on days 1 & 8
- Vinorelbine (Navelbine) 30 mg/m2 IV over 6 to 10 minutes once on days 1 & 8
- Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
28-day cycle x 4 cycles
References
- Naqi N, Ahmad S, Shah I, Khattak J. A multicentre phase-II feasibility study evaluating gemcitabine/vinorelbine / prednisolone combination chemotherapy in relapsed / refractory Hodgkin's lymphoma. J Coll Physicians Surg Pak. 2013 Jun;23(6):397-400. PubMed
ICE
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ICE: Ifosfamide, Carboplatin, Etoposide
Regimen
Phase II
- Ifosfamide (Ifex) 5 g/m2 IV continuous infusion over 24 hours on day 2; mixed in same solution as Mesna (Mesnex)
- Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg) IV once on day 2
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Supportive medications:
- Mesna (Mesnex) 5 g/m2 IV continuous infusion over 24 hours on day 2; mixed in same solution as Ifosfamide (Ifex)
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 5 to 12
- No dose reductions--treatment is delayed until ANC is >1000 and platelets >50 x 10^3
Q14days x 2 cycles
References
- Moskowitz CH, Nimer SD, Zelenetz AD, Trippett T, Hedrick EE, Filippa DA, Louie D, Gonzales M, Walits J, Coady-Lyons N, Qin J, Frank R, Bertino JR, Goy A, Noy A, O'Brien JP, Straus D, Portlock CS, Yahalom J. A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood. 2001 Feb 1;97(3):616-23. link to original article contains protocol PubMed
IGEV
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IGEV: Ifosfamide, GEmcitabine, Vinorelbine
Regimen
Phase II
- Ifosfamide (Ifex) 2000 mg/m2 IV over 2 hours once per day on days 1 to 4
- Gemcitabine (Gemzar) 800 mg/m2 IV once per day on days 1 to 4
- Vinorelbine (Navelbine) 20 mg/m2 IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 4
Supportive medications:
- 2L saline solution hyperhydration days 1 to 4
- Mesna (Mesnex) 2600 mg/m2 IV once per day on days 1 to 4
- Filgrastim (Neupogen) (dose not specified, but could assume 5 mcg/kg) SC once per day on days 7 to 12, or up to apheresis in the course of stem cell mobilization
Q21days x 4 cycles
References
- Santoro A, Magagnoli M, Spina M, Pinotti G, Siracusano L, Michieli M, Nozza A, Sarina B, Morenghi E, Castagna L, Tirelli U, Balzarotti M. Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin's lymphoma. Haematologica. 2007 Jan;92(1):35-41. link to original article contains protocol PubMed
MINE
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MINE: Mesna, Ifosfamide, Novantrone, Etoposide
Regimen
Phase II
- Mesna (Mesnex) 1.33 g/m2 IV over 1 hour on days 1 to 3; mixed in same solution as Ifosfamide (Ifex)
- Mesna (Mesnex) 500 mg PO 4 hours after each IV dose of Ifosfamide (Ifex) days 1 to 3
- Ifosfamide (Ifex) 1.33 g/m2 IV over 1 hour on days 1 to 3; mixed in same solution as Mesna (Mesnex)
- Mitoxantrone (Novantrone) 8 mg/m2 IV once on day 1
- Etoposide (Vepesid) 65 mg/m2 IV over 1 hour on days 1 to 3
Q21 to 28 days x up to 6 cycles in responding patients
References
- Rodriguez MA, Cabanillas FC, Hagemeister FB, McLaughlin P, Romaguera JE, Swan F, Velasquez W. A phase II trial of mesna/ifosfamide, mitoxantrone and etoposide for refractory lymphomas. Ann Oncol. 1995 Jul;6(6):609-11. link to original article contains protocol PubMed
Mini-BEAM
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BEAM: BiCNU, Etoposide, Ara-C, Melphalan
Regimen #1, Fernández-Jiménez et al. 1999 & Martín et al. 2001
Phase II
- Carmustine (BiCNU) 60 mg/m2 IV once on day 1
- Etoposide (Vepesid) 300 mg/m2 IV once on day 1
- Cytarabine (Cytosar) 800 mg/m2 IV once on day 1
- Melphalan (Alkeran) 30 mg/m2 IV once on day 1
4-week cycle x 2 to 3 cycles
Regimen #2, Colwill et al. 1995
Phase II
- Carmustine (BiCNU) 60 mg/m2 IV over 30 minutes once on day 1
- Etoposide (Vepesid) 75 mg/m2 IV over 30 minutes once per day on days 2 to 5
- Cytarabine (Cytosar) 100 mg/m2 IV Q12H on days 2 to 5
- Melphalan (Alkeran) 30 mg/m2 IV over 15 minutes once on day 6
Supportive medications:
- If febrile neutropenia occurred during previous cycle: Ciprofloxacin (Cipro) 500 mg PO once per day
- Patients were transfused to keep Hb =8, platelets =20
- There was no routine use of G-CSF or GM-CSF
Q4 to 6 weeks x 2 cycles prior to intensive therapy and autologous bone marrow transplantation
References
- Colwill R, Crump M, Couture F, Danish R, Stewart AK, Sutton DM, Scott JG, Sutcliffe SB, Brandwein JM, Keating A. Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease before intensive therapy and autologous bone marrow transplantation. J Clin Oncol. 1995 Feb;13(2):396-402. link to original article contains protocol PubMed
- Fernández-Jiménez MC, Canales MA, Ojeda E, de Bustos JG, Aguado MJ, Hernández-Navarro F. Salvage chemotherapy with mini-BEAM for relapsed or refractory Hodgkin's disease prior to autologous peripheral blood stem cell transplantation. Haematologica. 1999 Nov;84(11):1007-11. link to original article contains verified protocol PubMed
- Update: Martín A, Fernández-Jiménez MC, Caballero MD, Canales MA, Pérez-Simón JA, García de Bustos J, Vázquez L, Hernández-Navarro F, San Miguel JF. Long-term follow-up in patients treated with Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease. Br J Haematol. 2001 Apr;113(1):161-71. link to original article contains protocol PubMed
Sirolimus & Vorinostat
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Regimen
Non-randomized
This is a very heavily pre-treated cohort, median of 6 prior therapies; doses here are one level below MTD and are proposed as the ongoing doses to be studied.
- Sirolimus (Rapamune) 4 mg PO once per day
- Vorinostat (Zolinza) 300 mg once per day on days 7 to 28 of cycle 1, days 1 to 28 of subsequent cycles
28-day cycles
References
- Abstract: Filip Janku, Yasuhiro Oki, Gerald Steven Falchook, Vivek Subbiah, Aung Naing, Vivianne Marie Velez Bravo, David S. Hong, Jason R. Westin, Cesar Nunez, Luis Fayad, Sattva Swarup Neelapu, Larry W. Kwak, Elizabeth J. Shpall, Jennifer J. Wheler, Tamara Barnes, Winnie S. Liang, Bodour Salhia, Funda Meric-Bernstam, Razelle Kurzrock, Michelle A. Fanale. Activity of the mTOR inhibitor sirolimus and HDAC inhibitor vorinostat in heavily pretreated refractory Hodgkin lymphoma patients. J Clin Oncol 32:5s, 2014 (suppl; abstr 8508) link to original abstract
Consolidation and/or maintenance after salvage therapy
Allogeneic stem cell transplant
Usually reserved for patients relapsing after autologous stem cell transplant, and then for younger and very fit individuals. The regimens below have been specifically studied in the setting of relapsed/refractory Hodgkin lymphoma; for other regimens please go to the transplant conditioning regimens page.
Regimen #1
To be completed. Treatment preceded by salvage brentuximab vedotin.
Regimen #2
Study | Evidence |
Sureda et al. 2011 | Phase II |
Treatment preceded by DHAP x 2.
- Fludarabine (Fludara) 150 mg/m2 IV once per day on days -8 to -4
- Melphalan (Alkeran) 140 mg/m2 IV once per day on days -3 & -2
Recipients of stem cells from matched unrelated donors also received:
- Antithymocyte globulin (ATG) 45 mg/kg IV once per day on days -4 to -2
Graft-versus-host disease prophylaxis
- Cyclosporine A (not specified whether modified or non-modified) starting at 1.5 mg/kg BID IV on day -2
- Methotrexate (MTX) 10 mg/m2 IV once per day on days +1, +3, +6, +11
If no acute GVHD of grade 2 or more, cyclosporine A is tapered down by 10% per week starting on day +90 with planned discontinuation by day +180.
Regimen #3
Study | Evidence |
Anderlini et al. 2008 | Phase II |
Patients had "chemosensitive or stable disease after salvage treatment." The regimen as reported here is what the authors were using towards the end of the study period; see paper for details.
- Fludarabine (Fludara) 33 mg/m2 IV once per day on days -5 to -2
- Melphalan (Alkeran) 70 mg/m2 IV once per day on days -3 & -2
Recipients of stem cells from matched unrelated donors also received:
- Antithymocyte globulin (ATG) 2 mg/kg IV once per day on days -4 to -2
Graft-versus-host disease prophylaxis
- Tacrolimus (Prograf) IV starting on day -2, dosed to achieve serum levels 4–12 ng/mL and switched to PO as soon as possible. Continued for at least 6 months and then "tapered off" (instructions not given).
- Methotrexate (MTX) 5 mg/m2 IV once per day on days +1, +3, +6 (extra dose on day +11 for MUD recipients)
Regimen #4
Study | Evidence |
Sobol et al. 2013 | Phase II |
BEAM is the preparative regimen; further details not available in the abstract.
References
- Alvarez I, Sureda A, Caballero MD, Urbano-Ispizua A, Ribera JM, Canales M, García-Conde J, Sanz G, Arranz R, Bernal MT, de la Serna J, Díez JL, Moraleda JM, Rubió-Félix D, Xicoy B, Martínez C, Mateos MV, Sierra J. Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol. Biol Blood Marrow Transplant. 2006 Feb;12(2):172-83. link to original article contains protocol PubMed
- Anderlini P, Saliba R, Acholonu S, Giralt SA, Andersson B, Ueno NT, Hosing C, Khouri IF, Couriel D, de Lima M, Qazilbash MH, Pro B, Romaguera J, Fayad L, Hagemeister F, Younes A, Munsell MF, Champlin RE. Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin's lymphoma: the updated M.D. Anderson Cancer Center experience. Haematologica. 2008 Feb;93(2):257-64. Epub 2008 Jan 26. link to original article contains verified protocol PubMed
- Sureda A, Canals C, Arranz R, Caballero D, Ribera JM, Brune M, Passweg J, Martino R, Valcárcel D, Besalduch J, Duarte R, León A, Pascual MJ, García-Noblejas A, López Corral L, Xicoy B, Sierra J, Schmitz N. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin's lymphoma. Results of the HDR-ALLO study - a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2012 Feb;97(2):310-7. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- Sobol U, Rodriguez T, Smith S, Go A, Vimr R, Parthasarathy M, Guo R, Stiff P. Seven-year follow-up of allogeneic transplant using BCNU, etoposide, cytarabine and melphalan chemotherapy in patients with Hodgkin lymphoma after autograft failure: importance of minimal residual disease. Leuk Lymphoma. 2014 Jun;55(6):1281-7. Epub 2013 Oct 3. link to original article PubMed
- Illidge T, Bouabdallah R, Chen R, Gopal AK, Moskowitz CH, Ramchandren R, Shustov AR, Tilly H, Trippett TM, Gibb A, Grove LE, Advani R. Allogeneic transplant following brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Leuk Lymphoma. 2015 Jan 21:1-8. [Epub ahead of print] link to original article PubMed
Autologous stem cell transplant
To be completed. Usually preceded by a high-intensity salvage chemotherapy. See details about preparative regimens.
Nodular lymphocyte predominant Hodgkin Lymphoma
- Regimens can be found on the separate Nodular lymphocyte-predominant Hodgkin Lymphoma page