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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main RCC page for current regimens.

0 regimens on this page 0 variants on this page

Metastatic disease, first-line

Interferon alfa-2a & Interleukin-2

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Negrier et al. 1998	1992-1995	Phase 3 (E-esc)	1. HD IL-2 2. Interferon alfa-2a	Superior EFS
Passalacqua et al. 2009	1998-2003	Phase 3 (C)	IFN & IL-2; maintenance	Did not meet primary endpoint of OS
Négrier et al. 2008 (LEONB-PERCY-DUO)	2000-2005	Phase 3 (C)	IFN & IL-2; IV IL-2	Did not meet primary endpoint of OS

Immunotherapy

References

Négrier S, Escudier B, Lasset C, Douillard JY, Savary J, Chevreau C, Ravaud A, Mercatello A, Peny J, Mousseau M, Philip T, Tursz T; Groupe Français d'Immunothérapie. Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. N Engl J Med. 1998 Apr 30;338(18):1272-8. link to original article PubMed
LEONB-PERCY-DUO: Négrier S, Perol D, Ravaud A, Bay JO, Oudard S, Chabaud S, Fargeot P, Delva R, Deplanque G, Gravis G, Escudier B; French Immunotherapy Group. Randomized study of intravenous versus subcutaneous interleukin-2, and IFNalpha in patients with good prognosis metastatic renal cancer. Clin Cancer Res. 2008 Sep 15;14(18):5907-12. link to original article PubMed NCT00416871
Passalacqua R, Buzio C, Buti S, Porta C, Labianca R, Pezzuolo D, Camisa R, Sabbatini R, Benecchi L, Messina C, Cengarle R, Vaglio A, Dalla Chiesa M, Tomasello G, Caminiti C. Phase III, randomised, multicentre trial of maintenance immunotherapy with low-dose interleukin-2 and interferon-alpha for metastatic renal cell cancer. Cancer Immunol Immunother. 2010 Apr;59(4):553-61. Epub 2009 Sep 25. link to original article PubMed

Interferon alfa-2b monotherapy

Regimen

Study	Years of enrollment	Evidence
Flanigan et al. 2001 (SWOG 8949)	1991-1998	Non-randomized portion of RCT
Mickisch et al. 2001 (EORTC 30947)	1995-1998	Non-randomized portion of RCT

Preceding treatment

Nephrectomy versus no preceding treatment

Immunotherapy

Interferon alfa-2b (Intron-A)

References

EORTC 30947: Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R; EORTC Genitourinary Group. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. 2001 Sep 22;358(9286):966-70. link to original article PubMed
SWOG 8949: Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, Caton JR Jr, Munshi N, Crawford ED. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001 Dec 6;345(23):1655-9. link to original article PubMed
ECOG E2898: NCT00005966

Medroxyprogesterone monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ritchie et al. 1999 (MRC RE01)	1992-1997	Phase 3 (C)	IFN alfa-2a	Seems to have inferior OS
Negrier et al. 2007 (PERCY Quattro)	2000-2004	Phase 3 (C)	1. IFN alfa-2a 2. IFN alfa-2a & IL-2 3. IL-2	Did not meet primary endpoint of OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Hormone replacement therapy

Medroxyprogesterone (MPA)

References

MRC RE01: Ritchie A, Griffiths G, Parmar M; Medical Research Council Renal Cancer Collaborators. Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Lancet. 1999 Jan 2;353(9146):14-7. link to original article contains dosing details in abstract PubMed
PERCY Quattro: Negrier S, Perol D, Ravaud A, Chevreau C, Bay JO, Delva R, Sevin E, Caty A, Escudier B; French Immunotherapy Intergroup. Medroxyprogesterone, interferon alfa-2a, interleukin 2, or combination of both cytokines in patients with metastatic renal carcinoma of intermediate prognosis: results of a randomized controlled trial. Cancer. 2007 Dec 1;110(11):2468-77. link to original article PubMed NCT00416429

Vinblastine monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Pyrhönen et al. 1999	1988-1994	Phase 3 (C)	Vinblastine & IFN alfa-2a	Inferior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Vinblastine (Velban)

References

Pyrhönen S, Salminen E, Ruutu M, Lehtonen T, Nurmi M, Tammela T, Juusela H, Rintala E, Hietanen P, Kellokumpu-Lehtinen PL. Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol. 1999 Sep;17(9):2859-67. link to original article PubMed

Metastatic disease, second-line

FC, then allo HSCT

FC: Fludarabine & Cyclophosphamide

Regimen

Study	Evidence
Childs et al. 2000	Non-randomized, <20 pts

Chemotherapy

Fludarabine (Fludara) 25 mg/m² IV once per day on days -5 to -1
Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -7 & -6

Immunotherapy

Allogeneic stem cells transfused on day 0

One course

References

Childs R, Chernoff A, Contentin N, Bahceci E, Schrump D, Leitman S, Read EJ, Tisdale J, Dunbar C, Linehan WM, Young NS, Clave E, Epperson D, Mayo V, Barrett AJ. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med. 2000 Sep 14;343(11):750-8. link to original article contains dosing details in manuscript PubMed

Interferon alfa-2a monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Aass et al. 2005 (EORTC 30951)	1998-2001	Phase 3 (C)	IFN alfa-2a & Isotretinoin	Seems to have inferior OS

Immunotherapy

Interferon alfa-2a (Roferon-A)

References

EORTC 30951: Aass N, De Mulder PH, Mickisch GH, Mulders P, van Oosterom AT, van Poppel H, Fossa SD, de Prijck L, Sylvester RJ. Randomized phase II/III trial of interferon alfa-2a with and without 13-cis-retinoic acid in patients with progressive metastatic renal cell Carcinoma: the European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951). J Clin Oncol. 2005 Jun 20;23(18):4172-8. link to original article PubMed NCT00002737

Interferon alfa-2a & Isotretinoin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Aass et al. 2005 (EORTC 30951)	1998-2001	Phase 3 (E-esc)	IFN alfa-2a	Seems to have superior OS

Immunotherapy

References

EORTC 30951: Aass N, De Mulder PH, Mickisch GH, Mulders P, van Oosterom AT, van Poppel H, Fossa SD, de Prijck L, Sylvester RJ. Randomized phase II/III trial of interferon alfa-2a with and without 13-cis-retinoic acid in patients with progressive metastatic renal cell Carcinoma: the European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951). J Clin Oncol. 2005 Jun 20;23(18):4172-8. link to original article PubMed NCT00002737

Interferon alfa-2c monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
De Mulder et al. 1995 (EORTC 30885)	1988-1990	Phase 3 (C)	IFN alfa-2c & IFN gamma	Did not meet efficacy endpoints

Immunotherapy

Interferon alfa-2c (Berofor)

References

EORTC 30885: De Mulder PH, Oosterhof G, Bouffioux C, van Oosterom AT, Vermeylen K, Sylvester R; EORTC Genitourinary Group. EORTC (30885) randomised phase III study with recombinant interferon alpha and recombinant interferon alpha and gamma in patients with advanced renal cell carcinoma. Br J Cancer. 1995 Feb;71(2):371-5. link to original article link to PMC article PubMed

Megestrol monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ravaud et al. 2008	2002-2005	Phase 3 (C)	Lapatinib	Did not meet primary endpoint of TTP

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Hormone replacement therapy

Megestrol (Megace)

References

Ravaud A, Hawkins R, Gardner JP, von der Maase H, Zantl N, Harper P, Rolland F, Audhuy B, Machiels JP, Pétavy F, Gore M, Schöffski P, El-Hariry I. Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial. J Clin Oncol. 2008 May 10;26(14):2285-91. link to original article PubMed

@@ Line 3: / Line 3: @@
 [[#top|Back to Top]]
 </div>
-{{#lst:Section editor transclusions|anhl}}
+The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Renal_cell_carcinoma|main RCC page]] for current regimens.
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
 |<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 |}
 {{TOC limit|limit=3}}
-''Note: these regimens have been studied specifically in primary mediastinal B-cell lymphoma. Other large B-cell lymphoma regimens, such as those used in [[diffuse large B-cell lymphoma]] are also often used.''
+=Metastatic disease, first-line=
-=Guidelines=
+==Interferon alfa-2a & Interleukin-2 {{#subobject:77d26e|Regimen=1}}==
-==BSH==
-*'''2019:''' Cwynarski et al. [https://doi.org/10.1111/bjh.15731 The management of primary mediastinal B-cell lymphoma: a British Society for Haematology Good Practice Paper]
-==[http://www.esmo.org/ ESMO]==
-*'''2016:''' Vitolo et al. [http://annonc.oxfordjournals.org/content/27/suppl_5/v91.full.pdf+html Extranodal diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/27377716 PubMed]
-===Older===
-*'''2013:''' [http://annonc.oxfordjournals.org/content/24/3/561.full.pdf+html ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL)] [https://pubmed.ncbi.nlm.nih.gov/23175624 PubMed]
-==[https://www.nccn.org/ NCCN]==
-*[https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf NCCN Guidelines - B-cell Lymphomas]
-=Untreated=
-==DA-R-EPOCH {{#subobject:d7244e|Regimen=1}}==
-DA-R-EPOCH: '''<u>D</u>'''ose '''<u>A</u>'''djusted '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin (Vincristine), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:98dcb9|Variant=1}}===
+===Regimen {{#subobject:89bca8|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 20%" |Study
-!style="width: 33%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/NEJM199804303381805 Negrier et al. 1998]
+|1992-1995
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|1. [[Renal_cell_carcinoma#High-dose_Interleukin-2|HD IL-2]]<br>2. [[Renal_cell_carcinoma#Interferon_alfa-2a_monotherapy|Interferon alfa-2a]]
+| style="background-color:#1a9850" |Superior EFS
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4568999/ Dunleavy et al. 2013 (NCI 93-C-0133)]
+|[https://doi.org/10.1007/s00262-009-0773-9 Passalacqua et al. 2009]
-|1999-2012
+|1998-2003
-|style="background-color:#91cf61"|Phase 2
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Interferon_alfa-2a_.26_Interleukin-2|IFN & IL-2]]; maintenance
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[https://doi.org/10.1111/bjh.13273 Purroy et al. 2014]
+|[https://doi.org/10.1158/1078-0432.ccr-08-0236 Négrier et al. 2008 (LEONB-PERCY-DUO)]
-|2002-2008
+|2000-2005
-|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Interferon_alfa-2a_.26_Interleukin-2|IFN & IL-2]]; IV IL-2
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
+====Immunotherapy====
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 3 hours once on day 1
+*[[Interferon alfa-2a (Roferon-A)]]
-====Chemotherapy====
+*[[Aldesleukin (Proleukin)]]
-*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m<sup>2</sup>)
-*[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m<sup>2</sup>; dose was not capped)
-*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 2 hours once on day 5
-*[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>)
-====Glucocorticoid therapy====
-*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO twice per day on days 1 to 5
-====Supportive therapy====
-*[[Filgrastim (Neupogen)]] 300 mcg SC once per day, starting on day 6 and continuing until ANC greater than 5,000/uL past nadir
-*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg (or equivalent if allergic) PO once per day on 3 days per week
-**Note: It's assumed this is what the supplement for Dunleavy et al. 2013 meant by "Baxtrim (sulphametoxazole and trimethoprim)"
-*[[Omeprazole (Prilosec)]] 20 mg (or equivalent) PO once per day
-*[[Docusate (Colace)]] (dose not specified) and [[Sennosides (Senna)]] 2 tablets PO twice per day as needed for constipation
-*Lactulose 20 g PO every 6 hours as needed for constipation
-*Hepatitis B surface antigen positive patients received daily antiviral therapy until 8 weeks after completion of chemotherapy
-'''21-day cycle for 6 to 8 cycles'''
-====Dose modifications====
-*Start cycle 1 as described above.
-*Obtain CBCs twice per week for nadir measurements.
-*If nadir ANC greater than 500, increase etoposide, doxorubicin, and cyclophosphamide by one level (20%) compared to previous cycle.
-*If nadir ANC less than 500, use same doses as last cycle.
-*If nadir platelet count less than 25,000, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to the previous cycle.
 </div></div>
 ===References===
-# '''NCI 93-C-0133:''' Dunleavy K, Pittaluga S, Maeda LS, Advani R, Chen CC, Hessler J, Steinberg SM, Grant C, Wright G, Varma G, Staudt LM, Jaffe ES, Wilson WH. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013 Apr 11;368(15):1408-16. [https://doi.org/10.1056/NEJMoa1214561 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1214561/suppl_file/nejmoa1214561_appendix.pdf link to supplementary appendix] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4568999/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23574119 PubMed] NCT00001337
+#Négrier S, Escudier B, Lasset C, Douillard JY, Savary J, Chevreau C, Ravaud A, Mercatello A, Peny J, Mousseau M, Philip T, Tursz T; Groupe Français d'Immunothérapie. Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. N Engl J Med. 1998 Apr 30;338(18):1272-8. [https://doi.org/10.1056/NEJM199804303381805 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9562581 PubMed]
-# Purroy N, Bergua J, Gallur L, Prieto J, Lopez LA, Sancho JM, García-Marco JA, Castellví J, Montes-Moreno S, Batlle A, de Villambrosia SG, Carnicero F, Ferrando-Lamana L, Piris MA, Lopez A. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma: a phase II study conducted by the Spanish PETHEMA group. Br J Haematol. 2015 Apr;169(2):188-98. Epub 2014 Dec 18. [https://doi.org/10.1111/bjh.13273 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25521006 PubMed] EudraCT 2004-001684-22
+#'''LEONB-PERCY-DUO:''' Négrier S, Perol D, Ravaud A, Bay JO, Oudard S, Chabaud S, Fargeot P, Delva R, Deplanque G, Gravis G, Escudier B; French Immunotherapy Group. Randomized study of intravenous versus subcutaneous interleukin-2, and IFNalpha in patients with good prognosis metastatic renal cancer. Clin Cancer Res. 2008 Sep 15;14(18):5907-12. [https://doi.org/10.1158/1078-0432.ccr-08-0236 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18794104/ PubMed] NCT00416871
-==R-CHOP {{#subobject:796753|Regimen=1}}==
+#Passalacqua R, Buzio C, Buti S, Porta C, Labianca R, Pezzuolo D, Camisa R, Sabbatini R, Benecchi L, Messina C, Cengarle R, Vaglio A, Dalla Chiesa M, Tomasello G, Caminiti C. Phase III, randomised, multicentre trial of maintenance immunotherapy with low-dose interleukin-2 and interferon-alpha for metastatic renal cell cancer. Cancer Immunol Immunother. 2010 Apr;59(4):553-61. Epub 2009 Sep 25. [https://doi.org/10.1007/s00262-009-0773-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19779715 PubMed]
-R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
+==Interferon alfa-2b monotherapy {{#subobject:6b5be6|Regimen=1}}==
-<br>R-CHOP-21
-<br>CHOP-R
-===Example orders===
-*[[Example orders for R-CHOP in lymphoma]]
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:283715|Variant=1}}===
+===Regimen {{#subobject:39f1ab|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 20%"|Study
+!style="width: 33%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 33%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+|-
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|[https://doi.org/10.1056/NEJMoa003013 Flanigan et al. 2001 (SWOG 8949)]
+|1991-1998
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
-|[https://doi.org/10.1016/S1470-2045%2806%2970664-7 Pfreundschuh et al. 2006 (NCIC-CTG LY.9)]
+|[https://doi.org/10.1016/S0140-6736(01)06103-7 Mickisch et al. 2001 (EORTC 30947)]
-|2000-2003
+|1995-1998
-|style="background-color:#1a9851"|Phase 3 (E-esc)
+| style="background-color:#91cf61" |Non-randomized portion of RCT
-|1. [[#CHOP_88|CHOP]]<br>2. [[#CHOEP_88|CHOEP]]<br> 3. [[#MACOP-B_88|MACOP-B]]<br> 4. [[#PMitCEBO_88|PMitCEBO]]
-|style="background-color:#91cf60"|Seems to have superior EFS
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Renal_cell_carcinoma_surgery|Nephrectomy]] versus [[Surgery#No_surgery|no preceding treatment]]
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
+====Immunotherapy====
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+*[[Interferon alfa-2b (Intron-A)]]
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
-*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
-====Glucocorticoid therapy====
-*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
-====Supportive therapy====
-*G-CSF with one of the following:
-**[[Filgrastim (Neupogen)]] used at physician discretion for neutropenia
-**[[Lenograstim (Granocyte)]] used at physician discretion for neutropenia
-'''21-day cycle for 6 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#Radiation_therapy|Radiation therapy]]
 </div></div>
 ===References===
-# '''NCIC-CTG LY.9:''' Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648042 PubMed]
+#'''EORTC 30947:''' Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R; [[Study_Groups#EORTC|EORTC]] Genitourinary Group. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. 2001 Sep 22;358(9286):966-70. [https://doi.org/10.1016/S0140-6736(01)06103-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11583750 PubMed]
-## '''Subgroup analysis:''' Rieger M, Osterborg A, Pettengell R, White D, Gill D, Walewski J, Kuhnt E, Loeffler M, Pfreundschuh M, Ho AD; MabThera International Trial (MInT) Group. Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol. 2011 Mar;22(3):664-70. Epub 2010 Aug 19. [https://doi.org/10.1093/annonc/mdq418 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20724576 PubMed]
+#'''SWOG 8949:''' Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, Caton JR Jr, Munshi N, Crawford ED. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001 Dec 6;345(23):1655-9. [https://doi.org/10.1056/NEJMoa003013 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11759643 PubMed]
-==R-CHOP (Prednisolone) {{#subobject:7a9c53|Regimen=1}}==
+#'''ECOG E2898:''' NCT00005966
-R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisolone
+==Medroxyprogesterone monotherapy {{#subobject:6c7bb9|Regimen=1}}==
-===Example orders===
-*[[Example orders for R-CHOP in lymphoma]]
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:74f424|Variant=1}}===
+===Regimen {{#subobject:8b5e67|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 125: / Line 88: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1016/S0140-6736(13)60313-X Cunningham et al. 2013 (UK NCRI R-CHOP14v21)]
+|[https://doi.org/10.1016/S0140-6736(98)03544-2 Ritchie et al. 1999 (MRC RE01)]
-|2005-2008
+|1992-1997
-|style="background-color:#1a9851"|Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#R-CHOP-14_.28Prednisolone.29|R-CHOP-14]]
+|[[Renal_cell_carcinoma#Interferon_alfa-2a_monotherapy|IFN alfa-2a]]
-| style="background-color:#fee08b" |Might have inferior OS<sup>1</sup>
+| style="background-color:#fc8d59" |Seems to have inferior OS
+|-
+|[https://doi.org/10.1002/cncr.23056 Negrier et al. 2007 (PERCY Quattro)]
+|2000-2004
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[Renal_cell_carcinoma#Interferon_alfa-2a_monotherapy|IFN alfa-2a]]<br>2. [[#Interferon_alfa-2a_.26_Interleukin-2|IFN alfa-2a & IL-2]]<br>3. [[Renal_cell_carcinoma#Low-dose_Interleukin-2|IL-2]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-''<sup>1</sup>Reported efficacy is based on a post-hoc subgroup analysis.''
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
+====Hormone replacement therapy====
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+*[[Medroxyprogesterone (MPA)]]
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
-*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
-====Glucocorticoid therapy====
-*[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
-====CNS therapy, prophylaxis====
-Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:
-*[[Methotrexate (MTX)]] 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.
-====Supportive therapy====
-*[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12 at physician discretion
-*[[Allopurinol (Zyloprim)]] 300 mg PO once per day during cycle 1
-*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Co-trimoxazole]] 80/400 mg PO twice per day on 3 days per week, taken throughout therapy, ending 2 weeks after chemotherapy is completed
-'''21-day cycle for 8 cycles'''
 </div></div>
 ===References===
-# '''UK NCRI R-CHOP14v21:''' Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. [https://doi.org/10.1016/S0140-6736(13)60313-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23615461 PubMed] ISRCTN16017947
+#'''MRC RE01:''' Ritchie A, Griffiths G, Parmar M; Medical Research Council Renal Cancer Collaborators. Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Lancet. 1999 Jan 2;353(9146):14-7. [https://doi.org/10.1016/S0140-6736(98)03544-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10023944 PubMed]
-## '''Subgroup analysis:''' Gleeson M, Hawkes EA, Cunningham D, Chadwick N, Counsell N, Lawrie A, Jack A, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford J, McMillan A, Davies J, Turner D, Kruger A, Johnson PW, Gambell J, Linch D. Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) in the management of primary mediastinal B-cell lymphoma: a subgroup analysis of the UK NCRI R-CHOP 14 versus 21 trial. Br J Haematol. 2016 Nov;175(4):668-672. Epub 2016 Aug 1. [https://onlinelibrary.wiley.com/wol1/doi/10.1111/bjh.14287 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27477167 PubMed]
+#'''PERCY Quattro:''' Negrier S, Perol D, Ravaud A, Chevreau C, Bay JO, Delva R, Sevin E, Caty A, Escudier B; French Immunotherapy Intergroup. Medroxyprogesterone, interferon alfa-2a, interleukin 2, or combination of both cytokines in patients with metastatic renal carcinoma of intermediate prognosis: results of a randomized controlled trial. Cancer. 2007 Dec 1;110(11):2468-77. [https://doi.org/10.1002/cncr.23056 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17932908/ PubMed] NCT00416429
-==R-CHOP-14 (Prednisolone) {{#subobject:fc3bde|Regimen=1}}==
+==Vinblastine monotherapy {{#subobject:8c9fac|Regimen=1}}==
-R-CHOP-14: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisolone every '''<u>14</u>''' days
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:8136b1|Variant=1}}===
+===Regimen {{#subobject:5d6145|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 165: / Line 119: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1016/S0140-6736(13)60313-X Cunningham et al. 2013 (UK NCRI R-CHOP14v21)]
+|[https://doi.org/10.1200/JCO.1999.17.9.2859 Pyrhönen et al. 1999]
-|2005-2008
+|1988-1994
-|style="background-color:#1a9851"|Phase 3 (E-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#R-CHOP|R-CHOP-21]]
+|[[#Vinblastine_.26_Interferon_alfa-2a_88|Vinblastine & IFN alfa-2a]]
-| style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup>
+| style="background-color:#d73027" |Inferior OS
 |-
 |}
-''<sup>1</sup>Reported efficacy is based on the 2016 subgroup analysis.''
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 ====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+*[[Vinblastine (Velban)]]
-*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
-====Glucocorticoid therapy====
-*[[Prednisolone (Millipred)]] 100 mg PO once per day on days 1 to 5
-====CNS therapy, prophylaxis====
-Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:
-*[[Methotrexate (MTX)]] 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.
-====Supportive therapy====
-*[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12
-*[[Allopurinol (Zyloprim)]] 300 mg PO once per day during cycle 1
-*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Co-trimoxazole]] 480 mg (route not specified) twice per day on 3 days per week, taken throughout therapy, ending 2 weeks after treatment is completed
-'''14-day cycle for 6 cycles (8 cycles of rituximab)'''
 </div></div>
 ===References===
-# '''UK NCRI R-CHOP14v21:''' Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. [https://doi.org/10.1016/S0140-6736(13)60313-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23615461 PubMed] ISRCTN16017947
+# Pyrhönen S, Salminen E, Ruutu M, Lehtonen T, Nurmi M, Tammela T, Juusela H, Rintala E, Hietanen P, Kellokumpu-Lehtinen PL. Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol. 1999 Sep;17(9):2859-67. [https://doi.org/10.1200/JCO.1999.17.9.2859 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10561363 PubMed]
-## '''Subgroup analysis:''' Gleeson M, Hawkes EA, Cunningham D, Chadwick N, Counsell N, Lawrie A, Jack A, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford J, McMillan A, Davies J, Turner D, Kruger A, Johnson PW, Gambell J, Linch D. Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) in the management of primary mediastinal B-cell lymphoma: a subgroup analysis of the UK NCRI R-CHOP 14 versus 21 trial. Br J Haematol. 2016 Nov;175(4):668-672. Epub 2016 Aug 1. [https://onlinelibrary.wiley.com/wol1/doi/10.1111/bjh.14287 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27477167 PubMed]
+=Metastatic disease, second-line=
-=Consolidation after upfront therapy=
+==FC, then allo HSCT {{#subobject:1a1ed9|Regimen=1}}==
-==Radiation therapy {{#subobject:89ce8b|Regimen=1}}==
+FC: '''<u>F</u>'''ludarabine & '''<u>C</u>'''yclophosphamide
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:952fa4|Variant=1}}===
+===Regimen {{#subobject:9ce8f1|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 50%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1016/S1470-2045%2806%2970664-7 Pfreundschuh et al. 2006 (NCIC-CTG LY.9)]
+|[https://doi.org/10.1056/NEJM200009143431101 Childs et al. 2000]
-| style="background-color:#91cf61" |Non-randomized portion of RCT
+| style="background-color:#ffffbe" |Non-randomized, <20 pts
 |-
 |}
-<div class="toccolours" style="background-color:#cbd5e8">
+{{#lst:Allogeneic HSCT|9ce8f1}}
-====Preceding treatment====
-*[[#CHOP|CHOP]] x 6 or [[#CHOEP-21|CHOEP-21]] x 6 or [[#PMitCEBO|PMitCEBO]] x 6 or [[#MACOP-B|MACOP-B]] x 6 versus [[#R-CHOP|R-CHOP]] x 6 or [[#R-CHOEP-21|R-CHOEP-21]] x 6 or [[#R-PMitCEBO|R-PMitCEBO]] x 6 or [[#R-MACOP-B|R-MACOP-B]] x 6
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
-*[[External beam radiotherapy]]: 30 to 40 Gy given to sites of primary bulky disease; 30 to 40 Gy to primary extranodal disease at physician discretion
 </div></div>
 ===References===
-# '''NCIC-CTG LY.9:''' Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648042 PubMed] NCT00064116
+#Childs R, Chernoff A, Contentin N, Bahceci E, Schrump D, Leitman S, Read EJ, Tisdale J, Dunbar C, Linehan WM, Young NS, Clave E, Epperson D, Mayo V, Barrett AJ. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med. 2000 Sep 14;343(11):750-8. [https://doi.org/10.1056/NEJM200009143431101 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10984562 PubMed]
-## '''Subgroup analysis:''' Rieger M, Osterborg A, Pettengell R, White D, Gill D, Walewski J, Kuhnt E, Loeffler M, Pfreundschuh M, Ho AD; MabThera International Trial (MInT) Group. Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol. 2011 Mar;22(3):664-70. Epub 2010 Aug 19. [https://doi.org/10.1093/annonc/mdq418 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20724576 PubMed]
+==Interferon alfa-2a monotherapy {{#subobject:8f04d6|Regimen=1}}==
-=Relapsed or refractory, salvage therapy=
-==R-DHAP {{#subobject:26123c|Regimen=1}}==
-R-DHAP: '''<u>R</u>'''ituximab, '''<u>D</u>'''examethasone, '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:2ed78f|Variant=1}}===
+===Regimen {{#subobject:b28245|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!Study
+!style="width: 20%"|Study
-![[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Years of enrollment
-!Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2013.53.9593 Crump et al. 2014 (NCIC-CTG LY.12)]
+|[https://doi.org/10.1200/JCO.2005.07.114 Aass et al. 2005 (EORTC 30951)]
-|style="background-color:#91cf61"|Phase 3, <20 pts in subgroup (C)
+|1998-2001
-|[[Primary_mediastinal_B-cell_lymphoma#R-GDP|R-GDP]]
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Interferon_alfa-2a_.26_Isotretinoin|IFN alfa-2a & Isotretinoin]]
+| style="background-color:#fc8d59" |Seems to have inferior OS
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
+====Immunotherapy====
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+*[[Interferon alfa-2a (Roferon-A)]]
-====Glucocorticoid therapy====
-*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
-====Chemotherapy====
-*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
-'''21-day cycle for up to 3 cycles'''
 </div></div>
 ===References===
-<!-- Presented in part at the Annual Meeting of the American Society of Hematology, Atlanta, GA, December 7-10, 2013, and the International Conference on Malignant Lymphoma, Lugano, Switzerland, June 19-22, 2013. -->
+# '''EORTC 30951:''' Aass N, De Mulder PH, Mickisch GH, Mulders P, van Oosterom AT, van Poppel H, Fossa SD, de Prijck L, Sylvester RJ. Randomized phase II/III trial of interferon alfa-2a with and without 13-cis-retinoic acid in patients with progressive metastatic renal cell Carcinoma: the European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951). J Clin Oncol. 2005 Jun 20;23(18):4172-8. [https://doi.org/10.1200/JCO.2005.07.114 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15961764 PubMed] NCT00002737
-# '''NCIC-CTG LY.12:''' Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. [https://doi.org/10.1200/jco.2013.53.9593 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25267740 PubMed] NCT00078949
+==Interferon alfa-2a & Isotretinoin {{#subobject:8f038c|Regimen=1}}==
-==R-GDP {{#subobject:f6075a|Regimen=1}}==
-R-GDP: '''<u>R</u>'''ituximab, '''<u>G</u>'''emcitabine, '''<u>D</u>'''examethasone, '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:8091c0|Variant=1}}===
+===Regimen {{#subobject:b52145|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!Study
+!style="width: 20%"|Study
-![[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Years of enrollment
-!Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2013.53.9593 Crump et al. 2014 (NCIC-CTG LY.12)]
+|[https://doi.org/10.1200/JCO.2005.07.114 Aass et al. 2005 (EORTC 30951)]
-|style="background-color:#91cf61"|Phase 3, <20 pts in subgroup (E-switch-ic)
+|1998-2001
-|[[Primary_mediastinal_B-cell_lymphoma#R-DHAP|R-DHAP]]
+|style="background-color:#1a9851"|Phase 3 (E-esc)
-|-
+|[[#Interferon_alfa-2a_monotherapy|IFN alfa-2a]]
-|}
+| style="background-color:#91cf60" |Seems to have superior OS
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
-====Chemotherapy====
-*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
-====Glucocorticoid therapy====
-*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
-'''21-day cycle for up to 3 cycles'''
-</div></div>
-===References===
-<!-- Presented in part at the Annual Meeting of the American Society of Hematology, Atlanta, GA, December 7-10, 2013, and the International Conference on Malignant Lymphoma, Lugano, Switzerland, June 19-22, 2013. -->
-# '''NCIC-CTG LY.12:''' Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. [https://doi.org/10.1200/jco.2013.53.9593 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25267740 PubMed] NCT00078949
-=Consolidation after salvage therapy=
-==FluBuCy, then allo HSCT {{#subobject:84acb0|Regimen=1}}==
-FluBuCy: '''<u>Flu</u>'''darabine, '''<u>Bu</u>'''sulfan, '''<u>Cy</u>'''clophosphamide
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:bfe434|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1016/S1470-2045(14)70161-5 Glass et al. 2014 (DSHNHL R3)]
-| style="background-color:#91cf61" |Phase 2
-|-
-|}
-{{#lst:Allogeneic HSCT|bfe434}}
-</div></div>
-===References===
-<!-- # Glass B, rabbits Kamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N. High-dose chemotherapy Followed by allogeneic stem cell transplantation in relapsed and refractory high-risk aggressive non-Hodgkin's lymphoma: Results of a prospective study of the German high-grade non-Hodgkin's lymphoma study group. J Clin Oncol 30, 2012 (suppl; abstr 8004) -->
-# '''DSHNHL R3:''' Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. [https://doi.org/10.1016/S1470-2045(14)70161-5 link to original article] [http://www.dshnhl.org/app/download/9495510598/Studienprotokoll+DSHNHL+alloFBC+final+vollst.pdf link to original protocol (in German)] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24827808 PubMed] NCT00785330
-=Relapsed or refractory, further lines of therapy=
-==Axicabtagene ciloleucel monotherapy {{#subobject:78231d|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:e3e516|Variant=1}}===
-{| class="wikitable" style="color:white; background-color:#404040"
-|<small>'''FDA-recommended dose'''</small>
-|-
-|}
-{| class="wikitable sortable" style="width: 80%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|Years of enrollment
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363293/ Locke et al. 2017 (ZUMA-1)]
-|2015-2016
-|style="background-color:#ffffbe"|Phase 1/2, <20 pts in subgroup (RT)
-| style="background-color:#e0ecf4" |ORR: 82%
 |-
 |}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*Lymphodepletion with [[Autologous_HSCT#FC|FC]]
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
-*[[Axicabtagene ciloleucel (Yescarta)]] target dose of 2 × 10<sup>6</sup> CAR T cells/kg IV once on day 0
+*[[Interferon alfa-2a (Roferon-A)]]
-====Supportive therapy====
+*[[Isotretinoin (Accutane)]]
-*[[Acetaminophen (Tylenol)]] 650 mg PO once on day 0, approximately 60 minutes prior to [[Axicabtagene ciloleucel (Yescarta)]]
-*[[Diphenhydramine (Benadryl)]] 12.5 mg IV or PO once on day 0, approximately 60 minutes prior to [[Axicabtagene ciloleucel (Yescarta)]]
-'''One course; patients with initial response and disease progression at least 3 months later could be retreated'''
 </div></div>
 ===References===
-#'''ZUMA-1:''' Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. [https://doi.org/10.1016/j.ymthe.2016.10.020 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363293/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28129122 PubMed] NCT02348216
+# '''EORTC 30951:''' Aass N, De Mulder PH, Mickisch GH, Mulders P, van Oosterom AT, van Poppel H, Fossa SD, de Prijck L, Sylvester RJ. Randomized phase II/III trial of interferon alfa-2a with and without 13-cis-retinoic acid in patients with progressive metastatic renal cell Carcinoma: the European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951). J Clin Oncol. 2005 Jun 20;23(18):4172-8. [https://doi.org/10.1200/JCO.2005.07.114 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15961764 PubMed] NCT00002737
-##'''Update:''' Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10. [https://doi.org/10.1056/NEJMoa1707447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882485/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29226797 PubMed]
+==Interferon alfa-2c monotherapy {{#subobject:31b4d6|Regimen=1}}==
-##'''Update:''' Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. Epub 2018 Dec 2. [https://doi.org/10.1016/S1470-2045(18)30864-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733402/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30518502 PubMed]
-==Lisocabtagene maraleucel monotherapy {{#subobject:6e6u14|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:6nvha6|Variant=1}}===
+===Regimen {{#subobject:0f1524|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 33%"|Study
+!style="width: 20%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 20%"|Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1016/s0140-6736(20)31366-0 Abramson et al. 2020 (TRANSCEND NHL-001)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033601/ De Mulder et al. 1995 (EORTC 30885)]
-|2016-2019
+|1988-1990
-| style="background-color:#91cf61" |Phase 1 (RT)
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Interferon_alfa-2c_.26_Interferon_gamma_99|IFN alfa-2c & IFN gamma]]
+| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
-*[[Lisocabtagene maraleucel (Breyanzi)]]
+*[[Interferon alfa-2c (Berofor)]]
 </div></div>
 ===References===
-#'''TRANSCEND NHL-001:''' Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Albertson TM, Garcia J, Kostic A, Mallaney M, Ogasawara K, Newhall K, Kim Y, Li D, Siddiqi T. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839-852. Epub 2020 Sep 1. [https://doi.org/10.1016/s0140-6736(20)31366-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32888407 PubMed] NCT02631044
+# '''EORTC 30885:''' De Mulder PH, Oosterhof G, Bouffioux C, van Oosterom AT, Vermeylen K, Sylvester R; EORTC Genitourinary Group. EORTC (30885) randomised phase III study with recombinant interferon alpha and recombinant interferon alpha and gamma in patients with advanced renal cell carcinoma. Br J Cancer. 1995 Feb;71(2):371-5. [https://www.nature.com/articles/bjc199575 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033601/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/7841054 PubMed]
-==Pembrolizumab monotherapy {{#subobject:e0d17a|Regimen=1}}==
+==Megestrol monotherapy {{#subobject:4b50ea|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:7b36e9|Variant=1}}===
+===Regimen {{#subobject:52dc53|Variant=1}}===
-{| class="wikitable" style="color:white; background-color:#404040"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-|<small>'''FDA-recommended dose'''</small>
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|}
+|[https://doi.org/10.1200/JCO.2007.14.5029 Ravaud et al. 2008]
-{| class="wikitable" style="width: 60%; text-align:center;"
+|2002-2005
-!style="width: 33%"|Study
+|style="background-color:#1a9851"|Phase 3 (C)
-!style="width: 33%"|Years of enrollment
+|[[#Lapatinib_monotherapy_99|Lapatinib]]
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of TTP
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ Armand et al. 2016 (KEYNOTE-013)]
-|2014-2016
-|style="background-color:#91cf61"|Phase 1b
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ Armand et al. 2016 (KEYNOTE-170)]
-|2016-2017
-|style="background-color:#91cf61"|Phase 2 (RT)
 |-
 |}
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Immunotherapy====
+====Hormone replacement therapy====
-*[[Pembrolizumab (Keytruda)]] 200 mg IV over 30 minutes once on day 1
+*[[Megestrol (Megace)]]
-'''21-day cycle for up to 35 cycles (2 years)'''
 </div></div>
 ===References===
-<!-- # '''Abstract:''' J-M. Michot, P. Armand, W. Ding, V. Ribrag, B. Christian, A. Balakumaran, P. Marinello, S. Chlosta, Y. Zhang, M. Shipp, P.L. Zinzani; Pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma (rrPMBCL) or relapsed or refractory Richter syndrome (rrRS): Phase 2 KEYNOTE-170 study, Annals of Oncology, Volume 27, Issue suppl_6, 1 October 2016, 944TiP. [https://academic.oup.com/annonc/article/27/suppl_6/944TiP/2799681 link to abstract] -->
+# Ravaud A, Hawkins R, Gardner JP, von der Maase H, Zantl N, Harper P, Rolland F, Audhuy B, Machiels JP, Pétavy F, Gore M, Schöffski P, El-Hariry I. Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial. J Clin Oncol. 2008 May 10;26(14):2285-91. [https://doi.org/10.1200/JCO.2007.14.5029 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18467719 PubMed]
-# '''KEYNOTE-013:''' Armand P, Rodig S, Melnichenko V, Thieblemont C, Bouabdallah K, Tumyan G, Özcan M, Portino S, Fogliatto L, Caballero MD, Walewski J, Gulbas Z, Ribrag V, Christian B, Perini GF, Salles G, Svoboda J, Zain J, Patel S, Chen PH, Ligon AH, Ouyang J, Neuberg D, Redd R, Chatterjee A, Balakumaran A, Orlowski R, Shipp M, Zinzani PL. Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019 Dec 1;37(34):3291-3299. Epub 2019 Oct 14. [https://doi.org/10.1200/JCO.19.01389 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31609651 PubMed] NCT01953692
+[[Category:Renal cell carcinoma regimens]]
-# '''KEYNOTE-170:''' Armand P, Rodig S, Melnichenko V, Thieblemont C, Bouabdallah K, Tumyan G, Özcan M, Portino S, Fogliatto L, Caballero MD, Walewski J, Gulbas Z, Ribrag V, Christian B, Perini GF, Salles G, Svoboda J, Zain J, Patel S, Chen PH, Ligon AH, Ouyang J, Neuberg D, Redd R, Chatterjee A, Balakumaran A, Orlowski R, Shipp M, Zinzani PL. Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019 Dec 1;37(34):3291-3299. Epub 2019 Oct 14. [https://doi.org/10.1200/JCO.19.01389 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31609651 PubMed] NCT02576990
+[[Category:Historical regimens]]
-[[Category:Primary mediastinal B-cell lymphoma regimens]]
 [[Category:Disease-specific pages]]
-[[Category:Aggressive lymphomas]]
+[[Category:Genitourinary cancers]]
-[[Category:Non-Hodgkin lymphomas]]

Difference between revisions of "Staging page"

Revision as of 12:14, 29 October 2022

Metastatic disease, first-line

Interferon alfa-2a & Interleukin-2

Regimen

Immunotherapy

References

Interferon alfa-2b monotherapy

Regimen

Preceding treatment

Immunotherapy

References

Medroxyprogesterone monotherapy

Regimen

Hormone replacement therapy

References

Vinblastine monotherapy

Regimen

Chemotherapy

References

Metastatic disease, second-line

FC, then allo HSCT

Regimen

Chemotherapy

Immunotherapy

References

Interferon alfa-2a monotherapy

Regimen

Immunotherapy

References

Interferon alfa-2a & Isotretinoin

Regimen

Immunotherapy

References

Interferon alfa-2c monotherapy

Regimen

Immunotherapy

References

Megestrol monotherapy

Regimen

Hormone replacement therapy

References

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