Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
</div>
 
</div>
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{{#lst:Section editor transclusions|anhl}}
+
{{#lst:Section editor transclusions|gu}}
 +
''Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the [[Testicular_cancer_-_historical|historical regimens page]]. If you still can't find it, please let us know so we can add it!''
 +
<br>Note: Except for primary treatment for stage I seminoma, these regimens are generally applicable to seminoma and non-seminoma histologies.
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
|-
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|}
 
|}
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
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''The most common HIV-associated lymphomas are of [[Diffuse_large_B-cell_lymphoma|DLBCL]] or [[Burkitt lymphoma]] histology; plasmablastic lymphoma and primary effusion lymphomas are also frequently seen in advanced-stage HIV/AIDS. In patients with a normal CD4+ T-cell count and well-controlled HIV, the lymphoma is typically treated as per the histologic subtype. For others, regimens specific to HIV-associated lymphoma have been developed and are included here.''
+
=Guidelines=
−
=Untreated, pre-phase=
+
==[http://www.esmo.org/ ESMO]==
−
==CVP {{#subobject:1a817a|Regimen=1}}==
+
*'''2018:''' Honecker et al. [https://www.esmo.org/Guidelines/Genitourinary-Cancers/Testicular-germ-cell-cancer ESMO Consensus Conference Guidelines on testicular germ cell cancer: diagnosis, treatment and follow-up]
−
CVP: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
+
===Older===
−
<br>COP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
+
*'''2013:''' Oldenburg et al. [http://annonc.oxfordjournals.org/content/24/suppl_6/vi125.full.pdf+html Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.] [https://pubmed.ncbi.nlm.nih.gov/24078656 PubMed]
 +
==ESMO-EURACAN==
 +
*'''2022:''' Oldenburg et al. [https://doi.org/10.1016/j.annonc.2022.01.002 Testicular seminoma and non-seminoma: ESMO-EURACAN Clinical Practice Guideline for diagnosis, treatment and follow-up]
 +
==[https://www.nccn.org/ NCCN]==
 +
*[https://www.nccn.org/professionals/physician_gls/pdf/testicular.pdf NCCN Guidelines - Testicular Cancer]
 +
=Adjuvant therapy for resectable disease=
 +
==BEP {{#subobject:f1294e|Regimen=1}}==
 +
BEP: '''<u>B</u>'''leomycin, '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin)
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:865d9b|Variant=1}}===
+
===Regimen {{#subobject:14828f|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! 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.2007.12.0899 Albers et al. 2008 (AUO AH 01/94)]
 +
|1996-2005
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 +
|[[Surgery#RPLND|RPLND]]
 +
| style="background-color:#1a9850" |Superior RFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[Surgery#Orchiectomy|Orchiectomy]]
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Bleomycin (Blenoxane)]] 30 units IV bolus once per day on days 1, 8, 15
 +
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 +
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 +
'''15-day course'''
 +
</div></div>
 +
===References===
 +
#'''AUO AH 01/94:''' Albers P, Siener R, Krege S, Schmelz HU, Dieckmann KP, Heidenreich A, Kwasny P, Pechoel M, Lehmann J, Kliesch S, Köhrmann KU, Fimmers R, Weissbach L, Loy V, Wittekind C, Hartmann M; German Testicular Cancer Study Group. Randomized phase III trial comparing retroperitoneal lymph node dissection with one course of bleomycin and etoposide plus cisplatin chemotherapy in the adjuvant treatment of clinical stage I Nonseminomatous testicular germ cell tumors: AUO trial AH 01/94 by the German Testicular Cancer Study Group. J Clin Oncol. 2008 Jun 20;26(18):2966-72. Epub 2008 May 5. Erratum in: J Clin Oncol. 2010 Mar 10;28(8):1439. Dosage error in article text. [https://doi.org/10.1200/JCO.2007.12.0899 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18458040 PubMed]
 +
##'''Update:''' Hiester A, Fingerhut A, Niegisch G, Siener R, Krege S, Schmelz HU, Dieckmann KP, Heidenreich A, Kwasny P, Pechoel M, Lehmann J, Kliesch S, Köhrmann KU, Fimmers R, Loy V, Wittekind C, Hartmann M, Albers P. Late toxicities and recurrences in patients with clinical stage I non-seminomatous germ cell tumours after 1 cycle of adjuvant bleomycin, etoposide and cisplatin versus primary retroperitoneal lymph node dissection - A 13-year follow-up analysis of a phase III trial cohort. Eur J Cancer. 2021 Sep;155:64-72. Epub 2021 Aug 6. [https://doi.org/10.1016/j.ejca.2021.06.022 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34371444/ PubMed]
 +
==Carboplatin monotherapy {{#subobject:24be27|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1 {{#subobject:fcb329|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! 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/10.1016/S0140-6736(05)66984-X Oliver et al. 2005 (MRC TE19/EORTC 30982)]
 +
|1996-2001
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 +
|[[#Radiation_therapy|Radiation therapy]]
 +
| style="background-color:#eeee01" |Seems to have non-inferior RFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[Surgery#Orchiectomy|Orchiectomy]]
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 7 IV once on day 1
 +
**AUC 7 was described in Oliver et al. 2005 & Oliver et al. 2011 as [7 x (GFR + 25)] mg. eGFR was calculated by EDTA; if CrCl via 24-hour urine collection was used, 90% of the [7 x (GFR + 25)] mg dose was used. The Calvert formula for carboplatin dosing is: Dose (mg) = (target AUC) x (GFR + 25).
 +
'''One dose'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 2 doses carboplatin {{#subobject:8e690|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 25%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2005.01.9810 Aparicio et al. 2005 (Second Spanish Germ Cell Cancer Group study)]
 +
| style="background-color:#91cf61" |Non-randomized
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/110/8/2846.long Galicier et al. 2007 (LMB86)]
+
|[https://doi.org/10.1200/jco.2011.36.0503 Aparicio et al. 2011 (Third Spanish Germ Cell Cancer Group study)]
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#91cf61" |Non-randomized
 
|-
 
|-
 
|}
 
|}
 +
''Patients with stage I seminoma and local risk factors:''
 +
#''Tumor greater than 4 cm''
 +
#''Rete testis invasion''
 +
''Patients in Aparicio et al. 2005 had at least one risk factor; patients in Aparicio et al. 2011 had at both risk factors.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[Surgery#Orchiectomy|Orchiectomy]]
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup>/day IV once on day 1
+
*[[Carboplatin (Paraplatin)]] AUC 7 IV once on day 1
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
+
====Supportive therapy====
−
====Glucocorticoid therapy====
+
*[[Dexamethasone (Decadron)]]
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day IV or PO on days 1 to 7
+
*[[:Category:Serotonin_5-HT3_antagonists|5-hydroxytryptamine-3 (5-HT3) antagonists]]
 +
'''21-day cycle for 2 cycles'''
 +
</div></div>
 +
===References===
 +
#'''MRC TE19/EORTC 30982:''' Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, de Wit R, Aass N, Graham JD, Coleman R, Kirk SJ, Stenning SP; MRC; EORTC. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet. 2005 Jul 23-29;366(9482):293-300. [https://doi.org/10.1016/S0140-6736(05)66984-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16039331 PubMed] NCT00003014
 +
##'''Update:''' Oliver RT, Mead GM, Rustin GJ, Joffe JK, Aass N, Coleman R, Gabe R, Pollock P, Stenning SP. Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214). J Clin Oncol. 2011 Mar 10;29(8):957-62. Epub 2011 Jan 31. [https://doi.org/10.1200/jco.2009.26.4655 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21282539 PubMed]
 +
#'''Second Spanish Germ Cell Cancer Group study:''' Aparicio J, Germà JR, García del Muro X, Maroto P, Arranz JA, Sáenz A, Barnadas A, Dorca J, Gumà J, Olmos D, Bastús R, Carles J, Almenar D, Sánchez M, Paz-Ares L, Satrústegui JJ, Mellado B, Balil A, López-Brea M, Sánchez A; Spanish Germ Cell Cancer Cooperative Group. Risk-adapted management for patients with clinical stage I seminoma: the Second Spanish Germ Cell Cancer Cooperative Group study. J Clin Oncol. 2005 Dec 1;23(34):8717-23. Epub 2005 Oct 31. [https://doi.org/10.1200/jco.2005.01.9810 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16260698 PubMed]
 +
#'''Third Spanish Germ Cell Cancer Group study:''' Aparicio J, Maroto P, del Muro XG, Gumà J, Sánchez-Muñoz A, Margelí M, Doménech M, Bastús R, Fernández A, López-Brea M, Terrassa J, Meana A, del Prado PM, Sastre J, Satrústegui JJ, Gironés R, Robert L, Germà JR; Spanish Germ Cell Cancer Cooperative Group. Risk-adapted treatment in clinical stage I testicular seminoma: the third Spanish Germ Cell Cancer Group study. J Clin Oncol. 2011 Dec 10;29(35):4677-81. Epub 2011 Oct 31. [https://doi.org/10.1200/jco.2011.36.0503 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22042940 PubMed]
 +
==Radiation therapy==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! 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.2005.08.003 Jones et al. 2005 (MRC TE18/EORTC 30942)]
 +
|1995-1998
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Radiation_therapy|RT]]; lower-dose
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS24
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(05)66984-X Oliver et al. 2005 (MRC TE19/EORTC 30982)]
 +
|1996-2001
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_monotherapy|Carboplatin]]
 +
| style="background-color:#eeee01" |Seems to have non-inferior RFS
 +
|-
 +
|}
 +
''Note: radiation details are available in the references.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[Surgery#Orchiectomy|Orchiectomy]]
 
</div>
 
</div>
−
<div class="toccolours" style="background-color:#cbd5e7">
+
<div class="toccolours" style="background-color:#b3e2cd">
−
====Subsequent treatment====
+
====Radiotherapy====
−
*[[#COPADM|COPADM]] induction
+
*[[External beam radiotherapy]] 30 Gy (see note)
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''LMB86:''' Galicier L, Fieschi C, Borie R, Meignin V, Daniel MT, Gérard L, Oksenhendler E. Intensive chemotherapy regimen (LMB86) for St Jude stage IV AIDS-related Burkitt lymphoma/leukemia: a prospective study. Blood. 2007 Oct 15;110(8):2846-54. Epub 2007 Jul 3. [http://www.bloodjournal.org/content/110/8/2846.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17609431 PubMed]
+
#'''MRC TE18/EORTC 30942:''' Jones WG, Fossa SD, Mead GM, Roberts JT, Sokal M, Horwich A, Stenning SP; MRC; EORTC. Randomized trial of 30 versus 20 Gy in the adjuvant treatment of stage I testicular seminoma: a report on Medical Research Council Trial TE18, European Organisation for the Research and Treatment of Cancer Trial 30942 (ISRCTN18525328). J Clin Oncol. 2005 Feb 20;23(6):1200-8. [https://doi.org/10.1200/JCO.2005.08.003 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15718317 PubMed]
−
=Upfront therapy=
+
#'''MRC TE19/EORTC 30982:''' Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, de Wit R, Aass N, Graham JD, Coleman R, Kirk SJ, Stenning SP; MRC; EORTC. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet. 2005 Jul 23-29;366(9482):293-300. [https://doi.org/10.1016/S0140-6736(05)66984-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16039331 PubMed] NCT00003014
−
==CHOP {{#subobject:6bef2f|Regimen=1}}==
+
##'''Update:''' Oliver RT, Mead GM, Rustin GJ, Joffe JK, Aass N, Coleman R, Gabe R, Pollock P, Stenning SP. Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214). J Clin Oncol. 2011 Mar 10;29(8):957-62. Epub 2011 Jan 31. [https://doi.org/10.1200/jco.2009.26.4655 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21282539 PubMed]
−
CHOP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
+
=Upfront therapy for disseminated disease=
−
<br>CHOP-21: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone every '''<u>21</u>''' days
+
==BEP {{#subobject:d2918b|Regimen=1}}==
−
<br>ACOP
+
BEP: '''<u>B</u>'''leomycin, '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin)
−
<br>CAVP
+
<br>PVP16B: '''<u>P</u>'''latinol (Cisplatin), '''<u>VP-16</u>''' (Etoposide), '''<u>B</u>'''leomycin
−
<br>COPA
 
−
<br>VACP
 
−
<br>VCAP
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:f5ab10|Variant=1}}===
+
===Regimen variant #1, 90/500/100 x 3 ("standard" BEP) {{#subobject:3ffeed|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 20%"|Study
+
! style="width: 20%" |Study
−
!style="width: 20%"|Years of enrollment
+
! style="width: 20%" |Years of enrollment
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 20%"|Comparator
+
! style="width: 20%" |Comparator
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/jco.1989.7.3.387 Einhorn et al. 1989]
 +
|1984-1987
 +
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 +
|[[#BEP_2|BEP]] x 4
 +
| style="background-color:#eeee01" |Seems to have equivalent DFS
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(00)04165-9 Toner et al. 2001]
 +
|1994-2000
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Modified_BEP_99|Modified BEP]]; 30/360/100
 +
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1200/jco.2001.19.6.1629 de Wit et al. 2001]
 +
| rowspan="2" |1995-1998
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-de-esc)
 +
|1. [[#BEP_2|BEP]] x 4
 +
| style="background-color:#eeee01" |Equivalent PFS
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ Kaplan et al. 2005 (AMC010)]
+
|2. [[#BEP_2|BEP]]; 3-day etoposide x 3<br> 3. [[#BEP_2|BEP]]; 3-day etoposide x 4
−
|1998-2002
+
| style="background-color:#eeee01" |Equivalent PFS
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#R-CHOP|R-CHOP]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate
 
 
|-
 
|-
 
|}
 
|}
 +
''<sup>1</sup>Reported efficacy for Toner et al. 2001 is based on the 2010 update.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+
*[[Bleomycin (Blenoxane)]] 30 units IV bolus once per day on days 1, 8, 15
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> in 500 mL normal saline IV over 30 to 60 minutes once per day on days 1 to 5
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 to 5
−
====Glucocorticoid therapy====
+
'''21-day cycle for 3 cycles'''
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 90/500/100 x 4 ("standard" BEP) {{#subobject:4ffeed|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! 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/10.1056/NEJM198706043162302 Williams et al. 1987a]
 +
|1982-1984
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[Testicular_cancer_-_historical#BVP_2|BVP]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup>
 +
|-
 +
|[https://doi.org/10.1200/jco.1989.7.3.387 Einhorn et al. 1989]
 +
|1984-1987
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#BEP_2|BEP]] x 3
 +
| style="background-color:#eeee01" |Seems to have equivalent DFS
 +
|-
 +
|[https://doi.org/10.1200/jco.1998.16.4.1287 Nichols et al. 1998 (ECOG E3887)]
 +
|1987-1992
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#VIP|VIP]]
 +
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1200/jco.2001.19.6.1629 de Wit et al. 2001]
 +
| rowspan="2" |1995-1998
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#BEP_2|BEP]] x 3
 +
| style="background-color:#eeee01" |Equivalent PFS
 +
|-
 +
|2. [[#BEP_2|BEP]]; 3-day etoposide x 3<br> 3. [[#BEP_2|BEP]]; 3-day etoposide x 4
 +
| style="background-color:#eeee01" |Equivalent PFS
 +
|-
 +
|[https://doi.org/10.1200/jco.2007.13.8461 Culine et al. 2008 (T93MP)]
 +
|1994-2000
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Testicular_cancer_-_historical#CISCA.2FVB|CISCA/VB]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of FRR
 +
|-
 +
|[https://doi.org/10.1200/JCO.2005.05.4528 Motzer et al. 2007 (SWOG-9442)]
 +
|1994-2003
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#BEP_2|BEP]] x 2, then HDCT x 2
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of durable CR at 12 mo
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295568/ de Wit et al. 2012 (EORTC 30983)]
 +
|1998-2009
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#T-BEP_88|T-BEP]]
 +
| style="background-color:#fc8d59" |Seems to have inferior PFS36
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082158/ Daugaard et al. 2010 (EORTC 30974)]
 +
|1999-2007
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#BEP_2|BEP]] x 1, then HDCT x 3
 +
| style="background-color:#fee08b" |Might have inferior FFS
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400870/ Fizazi et al. 2014 (GETUG 13)]
 +
|2003-2012
 +
| style="background-color:#91cf61" |Risk-adapted therapy
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|}
 +
''<sup>1</sup>There seemed to be a survival advantage in the high tumor volume subgroup, but no difference was seen in the overall group.''<br>
 +
''Note: this was the favorable decline rate subset of GETUG 13.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Bleomycin (Blenoxane)]] 30 units IV bolus once per day on days 1, 8, 15
 +
**Note: Williams et al. 1987 gave bleomycin on days 2, 9, 16
 +
**Note: de Wit et al. 2001 only used bleomycin for cycles 1 to 3
 +
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> in 500 mL normal saline IV over 30 to 60 minutes once per day on days 1 to 5
 +
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 15 to 60 minutes once per day on days 1 to 5
 
====Supportive therapy====
 
====Supportive therapy====
−
*Combination antiretrovirals were required
+
*(as described in Nichols et al. 1998):
−
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 5 mcg/kg SC once per day from days 4 to 13 or until ANC greater than 10k/uL.
+
*Normal saline 100 mL/hour IV over 12 hours once per day on days 1 to 5, prior to [[Cisplatin (Platinol)]]
−
*PCP prophylaxis with ONE of the following:
+
*Normal saline 100 mL/hour IV throughout the 5 day course of [[Cisplatin (Platinol)]], ending 6 hours after each cycle's last cisplatin dose
−
**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] (dose/route/schedule not specified)
+
*[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] (type not specified) 5 mcg/kg SC once per day on days 7, 9 to 14, 16, 17
−
**[[Dapsone (Aczone)]] (dose/route/schedule not specified)
+
'''21-day cycle for 4 cycles'''
−
**[[Pentamidine (Nebupent)]] (dose/schedule not specified)
+
</div></div><br>
−
'''21-day cycle for 3 cycles for early disease, or minimum of 6 cycles or 2 past CR for advanced disease'''
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 90/495/100 x 3 (3-day etoposide) {{#subobject:2d07e5|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! 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]]
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1200/jco.2001.19.6.1629 de Wit et al. 2001]
 +
| rowspan="2" |1995-1998
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-de-esc)
 +
|1. [[#BEP_2|BEP]] x 3<br> 2. [[#BEP_2|BEP]] x 4
 +
| style="background-color:#eeee01" |Equivalent PFS
 +
|-
 +
|3. [[#BEP_2|BEP]]; 3-day etoposide x 4
 +
| style="background-color:#eeee01" |Equivalent PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Bleomycin (Blenoxane)]] 30 units IV once per day on days 1, 8, 15
 +
*[[Etoposide (Vepesid)]] 165 mg/m<sup>2</sup> IV once per day on days 1 to 3
 +
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 2
 +
'''21-day cycle for 3 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #4, 90/495/100 x 4 (3-day etoposide) {{#subobject:4d07e5|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! 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]]
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1200/jco.2001.19.6.1629 de Wit et al. 2001]
 +
| rowspan="2" |1995-1998
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|1. [[#BEP_2|BEP]] x 3<br> 2. [[#BEP_2|BEP]] x 4
 +
| style="background-color:#eeee01" |Equivalent PFS
 +
|-
 +
|3. [[#BEP_2|BEP]]; 3-day etoposide x 3
 +
| style="background-color:#eeee01" |Equivalent PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Bleomycin (Blenoxane)]] as follows:
 +
**Cycles 1 to 3: 30 units IV once per day on days 1, 8, 15
 +
*[[Etoposide (Vepesid)]] 165 mg/m<sup>2</sup> IV once per day on days 1 to 3
 +
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 2
 +
'''21-day cycle for 4 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #5, 45/500/100 (modified BEP) {{#subobject:fd61db|Variant=1}}===
 +
{| class="wikitable" style="width: 40%; text-align:center;"
 +
! style="width: 25%" |Study
 +
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361516/ Fosså et al. 2005 (EORTC 30948)]
 +
| style="background-color:#91cf61" |Phase 2
 +
|-
 +
|}
 +
''Note that the dose of bleomycin is lower than standard BEP.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[#C-BOP|C-BOP]] x 2, then [[#Bleomycin_.26_Vincristine_.28BO.29|BO]] x 1
 
</div>
 
</div>
−
<div class="toccolours" style="background-color:#cbd5e7">
+
<div class="toccolours" style="background-color:#b3e2cd">
−
====Subsequent treatment====
+
====Chemotherapy====
−
*Patients with stage I, IE, or nonbulky stage II disease: [[#Radiation_therapy|IFRT]], beginning 3 weeks after the third cycle of chemotherapy
+
*[[Bleomycin (Blenoxane)]] 15 mg IV once per day on days 1, 8, 15
 +
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
 +
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
 +
'''21-day cycle for 3 cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''AMC010:''' Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. [http://www.bloodjournal.org/content/106/5/1538.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15914552 PubMed] NCT00003595
+
#Williams SD, Birch R, Einhorn LH, Irwin L, Greco FA, Loehrer PJ. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med. 1987 Jun 4;316(23):1435-40. [https://doi.org/10.1056/NEJM198706043162302 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2437455 PubMed]
−
==CODOX-M {{#subobject:55e8f4|Regimen=1}}==
+
#Einhorn LH, Williams SD, Loehrer PJ, Birch R, Drasga R, Omura G, Greco FA; Southeastern Cancer Study Group. Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol. J Clin Oncol. 1989 Mar;7(3):387-91. [https://doi.org/10.1200/jco.1989.7.3.387 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2465391 PubMed]
−
CODOX-M: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate
+
##'''Update:''' Saxman SB, Finch D, Gonin R, Einhorn LH. Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide, and cisplatin in favorable-prognosis germ-cell tumors: the Indiana University experience. J Clin Oncol. 1998 Feb;16(2):702-6. [https://doi.org/10.1200/jco.1998.16.2.702 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9469360 PubMed]
 +
#'''ECOG E3887:''' Nichols CR, Catalano PJ, Crawford ED, Vogelzang NJ, Einhorn LH, Loehrer PJ. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol. 1998 Apr;16(4):1287-93. [https://doi.org/10.1200/jco.1998.16.4.1287 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9552027 PubMed] content property of [http://hemonc.org HemOnc.org]
 +
##'''Update:''' Hinton S, Catalano PJ, Einhorn LH, Nichols CR, Crawford ED, Vogelzang N, Trump D, Loehrer PJ Sr. Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors: final analysis of an intergroup trial. Cancer. 2003 Apr 15;97(8):1869-75. [https://doi.org/full/10.1002/cncr.11271 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12673712 PubMed]
 +
#Toner GC, Stockler MR, Boyer MJ, Jones M, Thomson DB, Harvey VJ, Olver IN, Dhillon H, McMullen A, Gebski VJ, Levi JA, Simes RJ; Australian and New Zealand Germ Cell Trial Group. Comparison of two standard chemotherapy regimens for good-prognosis germ-cell tumours: a randomised trial. Lancet. 2001 Mar 10;357(9258):739-45. [https://doi.org/10.1016/S0140-6736(00)04165-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11253966 PubMed]
 +
##'''Update:''' Grimison PS, Stockler MR, Thomson DB, Olver IN, Harvey VJ, Gebski VJ, Lewis CR, Levi JA, Boyer MJ, Gurney H, Craft P, Boland AL, Simes RJ, Toner GC. Comparison of two standard chemotherapy regimens for good-prognosis germ cell tumors: updated analysis of a randomized trial. J Natl Cancer Inst. 2010 Aug 18;102(16):1253-62. Epub 2010 Jul 14. [https://academic.oup.com/jnci/article/102/16/1253/2568956 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20631341 PubMed]
 +
#de Wit R, Roberts JT, Wilkinson PM, de Mulder PH, Mead GM, Fosså SD, Cook P, de Prijck L, Stenning S, Collette L; European Organisation for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group; MRC. Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized study of the European Organisation for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council. J Clin Oncol. 2001 Mar 15;19(6):1629-40. [https://doi.org/10.1200/jco.2001.19.6.1629 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11250991 PubMed]
 +
#'''EORTC 30948:''' Fosså SD, Paluchowska B, Horwich A, Kaiser G, de Mulder PH, Koriakine O, van Oosterom AT, de Prijck L, Collette L, de Wit R; [[Study_Groups#EORTC|EORTC]] GU Group. Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948). Br J Cancer. 2005 Nov 28;93(11):1209-14. [https://doi.org/10.1038/sj.bjc.6602830 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361516/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/16251877 PubMed]
 +
#'''SWOG-9442:''' Motzer RJ, Nichols CJ, Margolin KA, Bacik J, Richardson PG, Vogelzang NJ, Bajorin DF, Lara PN Jr, Einhorn L, Mazumdar M, Bosl GJ. Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors. J Clin Oncol. 2007 Jan 20;25(3):247-56. [https://doi.org/10.1200/JCO.2005.05.4528 link to original article] '''refers to Williams et al. 1998''' [https://pubmed.ncbi.nlm.nih.gov/17235042 PubMed] NCT00002596
 +
#'''T93MP:''' Culine S, Kramar A, Théodore C, Geoffrois L, Chevreau C, Biron P, Nguyen BB, Héron JF, Kerbrat P, Caty A, Delva R, Fargeot P, Fizazi K, Bouzy J, Droz JP; Genito-Urinary Group of the French Federation of Cancer Centers. Randomized trial comparing bleomycin/etoposide/cisplatin with alternating cisplatin/cyclophosphamide/doxorubicin and vinblastine/bleomycin regimens of chemotherapy for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP. J Clin Oncol. 2008 Jan 20;26(3):421-7. [https://doi.org/10.1200/jco.2007.13.8461 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18202419 PubMed]
 +
#'''EORTC 30974:''' Daugaard G, Skoneczna I, Aass N, De Wit R, De Santis M, Dumez H, Marreaud S, Collette L, Lluch JR, Bokemeyer C, Schmoll HJ. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer: an intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974). Ann Oncol. 2011 May;22(5):1054-61. Epub 2010 Nov 8. [https://doi.org/10.1093/annonc/mdq575 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082158/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21059637 PubMed] NCT00003941
 +
#'''EORTC 30983:''' de Wit R, Skoneczna I, Daugaard G, De Santis M, Garin A, Aass N, Witjes AJ, Albers P, White JD, Germa-Lluch JR, Marreaud S, Collette L. Randomized phase III  study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer: intergroup study EORTC 30983. J Clin Oncol. 2012 Mar 10;30(8):792-9. Epub 2012 Jan 23. [https://doi.org/10.1200/JCO.2011.37.0171 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295568/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22271474 PubMed] NCT00003643
 +
#'''GETUG 13:''' Fizazi K, Pagliaro L, Laplanche A, Fléchon A, Mardiak J, Geoffrois L, Kerbrat P, Chevreau C, Delva R, Rolland F, Theodore C, Roubaud G, Gravis G, Eymard JC, Malhaire JP, Linassier C, Habibian M, Martin AL, Journeau F, Reckova M, Logothetis C, Culine S. Personalised chemotherapy based on tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial. Lancet Oncol. 2014 Dec;15(13):1442-50. Epub 2014 Nov 13. [https://doi.org/10.1016/S1470-2045(14)70490-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400870/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25456363 PubMed] NCT00104676
 +
==Accelerated BEP {{#subobject:12c50c|Regimen=1}}==
 +
Accelerated BEP: Accelerated '''<u>B</u>'''leomycin, '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin)
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:637c6c|Variant=1}}===
+
===Regimen {{#subobject:275b81|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable" style="width: 60%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 33%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 33%" |Years of enrollment
 +
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1002/cncr.11628 Wang et al. 2003]
+
|[https://doi.org/10.1093/annonc/mdt369 Grimison et al. 2014]
−
|style="background-color:#ffffbe"|Retrospective
+
|2008-2010
 +
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
−
''Note: Wang et al. 2003 retrospectively identified 8 HIV+ Burkitt lymphoma patients who had undergone treatment with CODOX-M/IVAC per the NCI 77-04 protocol.''
+
<div class="toccolours" style="background-color:#b3e2cd">
−
*Patients are stratified into high and low risk:
 
−
**Low risk patients must fulfill all of the following criteria:
 
−
***Serum LDH within the institution's normal range (for the NCI, this was less than 350 IU/L)
 
−
***Single extraabdominal mass or completely resected abdominal disease
 
−
**Any patients which do not meet low risk criteria are classified as high risk
 
−
''This regimen is for low risk patients.''
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5
+
*[[Bleomycin (Blenoxane)]] by the following criteria:
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8
+
**Good prognosis: 30,000 IU once per week for 9 doses
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
+
**All others: 30,000 IU once per week for 12 doses
−
*[[Methotrexate (MTX)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 240 mg/m<sup>2</sup>/hour IV continuous infusion over 23 hours (total dose per cycle: 6720 mg/m<sup>2</sup>)
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
−
====CNS therapy, prophylaxis====
+
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
−
*[[Cytarabine (Ara-C)]] 70 mg IT once on day 1
 
−
**Patients younger than 3 years old received "appropriately reduced doses"
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 3
 
−
**Patients younger than 3 years old received "appropriately reduced doses"
 
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Folinic acid (Leucovorin)]] 192 mg/m<sup>2</sup> IV once on day 11, starting 36 hours after the start of the day 10 methotrexate, then 12 mg/m<sup>2</sup> IV every 6 hours thereafter until serum methotrexate level is less than 50 nmol/L
+
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 6
−
'''3 cycles; each cycle starts on the same day that the patient's ANC is greater than 1000/uL'''  
+
'''14-day cycle for 4 cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''Retrospective:''' Wang ES, Straus DJ, Teruya-Feldstein J, Qin J, Portlock C, Moskowitz C, Goy A, Hedrick E, Zelenetz AD, Noy A. Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer. 2003 Sep 15;98(6):1196-205. [https://doi.org/10.1002/cncr.11628 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12973843 PubMed]
+
#Grimison PS, Stockler MR, Chatfield M, Thomson DB, Gebski V, Friedlander M, Boland AL, Houghton B, Gurney H, Rosenthal M, Singhal N, Kichenadasse G, Wong SS, Lewis CR, Vasey PA, Toner GC; Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Accelerated BEP for metastatic germ cell tumours: a multicenter phase II trial by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). Ann Oncol. 2014 Jan;25(1):143-8. [https://doi.org/10.1093/annonc/mdt369 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24356625 PubMed] ACTRN 12607000294459
−
==CODOX-M/IVAC {{#subobject:4b6b9|Regimen=1}}==
+
==Bleomycin & Vincristine (BO) {{#subobject:f3d6ec|Regimen=1}}==
−
CODOX-M/IVAC: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate alternating with '''<u>I</u>'''fosfamide, '''<u>V</u>'''epesid (etoposide), '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine)
+
BO: '''<u>B</u>'''leomycin & '''<u>O</u>'''ncovin (Vincristine)
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:4140f7|Variant=1}}===
+
===Regimen {{#subobject:fa2436|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 25%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
|-
 
−
|[https://doi.org/10.1200/jco.1996.14.3.925 Magrath et al. 1996 (77-04)]
 
−
|style="background-color:#91cf61"|Phase 2
 
 
|-
 
|-
−
|[https://doi.org/10.1002/cncr.11628 Wang et al. 2003]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361516/ Fosså et al. 2005 (EORTC 30948)]
−
|style="background-color:#ffffbe"|Retrospective
+
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
−
''Note: the original protocol of Magrath et al. 1996 did not comment on HIV status. Wang et al. 2003 retrospectively identified 8 HIV+ Burkitt lymphoma patients who had undergone treatment with CODOX-M/IVAC.''
+
<div class="toccolours" style="background-color:#cbd5e8">
−
*Patients are stratified into high and low risk:
+
====Preceding treatment====
−
**Low risk patients must fulfill all of the following criteria:
+
*[[#C-BOP|C-BOP]] x 2
−
***Serum LDH within the institution's normal range (for the NCI, this was less than 350 IU/L)
+
</div>
−
***Single extraabdominal mass or completely resected abdominal disease
+
<div class="toccolours" style="background-color:#b3e2cd">
−
**Any patients which do not meet low risk criteria are classified as high risk
+
====Chemotherapy====
−
''This regimen is for high-risk patients.''
+
*[[Bleomycin (Blenoxane)]] 15 mg IV once per day on days 1 & 8
−
====Chemotherapy, Part A: CODOX-M====
+
*[[Vincristine (Oncovin)]] 2 mg IV once per day on days 1 & 8
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5
+
'''14-day cycle for 1 cycle'''
−
*[[Vincristine (Oncovin)]] as follows:
+
</div>
−
**Cycle 1: 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8
+
<div class="toccolours" style="background-color:#cbd5e7">
−
**Cycle 3: 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+
====Subsequent treatment====
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
+
[[#BEP_2|BEP]]; modified x 3
−
*[[Methotrexate (MTX)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 240 mg/m<sup>2</sup>/hour IV continuous infusion over 23 hours (total dose per cycle: 6720 mg/m<sup>2</sup>)
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 1 & 3
 
−
**Patients younger than 3 years old received "appropriately reduced doses"
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 15
 
−
**Patients younger than 3 years old received "appropriately reduced doses"
 
−
Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy during cycle 1:
 
−
*[[Cytarabine (Ara-C)]] 70 mg IT once on day 5 (in addition to doses above)
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 17 (in addition to dose above)
 
−
====Supportive therapy====
 
−
*[[Folinic acid (Leucovorin)]] 192 mg/m<sup>2</sup> IV once on day 11, starting 36 hours after the start of the day 10 methotrexate, then 12 mg/m<sup>2</sup> IV every 6 hours thereafter until serum methotrexate level is less than 50 nmol/L
 
−
*[[Sargramostim (Leukine)|GM-CSF]] 7.5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/uL
 
−
====Chemotherapy, Part B: IVAC====
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>)
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 5
 
−
Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy during cycle 2:
 
−
*[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 7 & 9
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 17 (in addition to dose above)
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup> IV every 3 hours on days 1 to 5, given at same time as [[Ifosfamide (Ifex)]]
 
−
*[[Sargramostim (Leukine)|GM-CSF]] 7.5 mcg/kg SC once per day, starting on day 7 and continuing until ANC greater than 1000/uL
 
−
'''4 cycles (see note)'''
 
−
''Note: CODOX-M and IVAC are given in an alternating fashion for a total of 4 cycles (A, B, A, B). Each cycle starts on the same day that the patient's ANC is greater than 1000/uL.''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Magrath I, Adde M, Shad A, Venzon D, Seibel N, Gootenberg J, Neely J, Arndt C, Nieder M, Jaffe E, Wittes RA, Horak ID. Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol. 1996 Mar;14(3):925-34. [https://doi.org/10.1200/jco.1996.14.3.925 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8622041 PubMed]
+
#'''EORTC 30948:''' Fosså SD, Paluchowska B, Horwich A, Kaiser G, de Mulder PH, Koriakine O, van Oosterom AT, de Prijck L, Collette L, de Wit R; [[Study_Groups#EORTC|EORTC]] GU Group. Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948). Br J Cancer. 2005 Nov 28;93(11):1209-14. [https://doi.org/10.1038/sj.bjc.6602830 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361516/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/16251877 PubMed]
−
# '''Retrospective:''' Wang ES, Straus DJ, Teruya-Feldstein J, Qin J, Portlock C, Moskowitz C, Goy A, Hedrick E, Zelenetz AD, Noy A. Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer. 2003 Sep 15;98(6):1196-205. [https://doi.org/10.1002/cncr.11628 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12973843 PubMed]
+
==C-BOP {{#subobject:61edd7|Regimen=1}}==
−
==dmCODOX-M - Modified Magrath {{#subobject:0a0210|Regimen=1}}==
+
C-BOP: '''<u>C</u>'''isplatin, '''<u>B</u>'''leomycin, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''araplatin (Carboplatin)
−
dmCODOX-M: '''<u>d</u>'''ose-'''<u>m</u>'''odified '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:a4c94b|Variant=1}}===
+
===Regimen {{#subobject:6d801b|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 20%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361516/ Fosså et al. 2005 (EORTC 30948)]
 +
|1996-1998
 +
| style="background-color:#91cf61" |Phase 2
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532802/ Mead et al. 2008 (MRC/NCRI LY10)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410298/ Huddart et al. 2014 (MRC TE23)]
−
|style="background-color:#91cf61"|Non-randomized
+
|2005-2009
 +
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 +
|[[#BEP_2|BEP]]
 +
| style="background-color:#91cf60" |Seems to have superior FRR
 
|-
 
|-
 
|}
 
|}
−
*Patients are stratified into high and low risk:
+
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
−
**Low risk patients must fulfill at least 3 of the following criteria:
+
<div class="toccolours" style="background-color:#b3e2cd">
−
***Normal LDH
 
−
***[[Performance_status#ECOG_performance_status_.28WHO.2FZubrod_score.29 | WHO performance status]] of 0 or 1
 
−
***Ann Arbor stage I or II
 
−
***0 or 1 extranodal sites of disease
 
−
**Any patients which do not meet low risk criteria are classified as high risk
 
−
''This regimen is for low risk patients.''
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5
+
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 2, then 40 mg/m<sup>2</sup> IV once on day 8
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8
+
*[[Vincristine (Oncovin)]] 2 mg IV once per day on days 1 & 8
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
+
*[[Bleomycin (Blenoxane)]] 15 mg IV once per day on days 1 & 8, then 15 mg/day IV continuous infusion over 120 hours, started on day 8 (total dose per cycle: 105 mg)
−
*[[Methotrexate (MTX)]] by the following age-based criteria:
+
*[[Carboplatin (Paraplatin)]] AUC 3 IV once on day 8
−
**Patients 65 years old or younger: 300 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 2700 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 3000 mg/m<sup>2</sup>)
+
'''14-day cycle for 2 cycles'''
−
**Patients older than 65 years old: 100 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 900 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 1000 mg/m<sup>2</sup>)
+
</div>
−
====CNS therapy, prophylaxis====
+
<div class="toccolours" style="background-color:#cbd5e7">
−
*[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 1 & 3
+
====Subsequent treatment====
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 15
+
*[[#Bleomycin_.26_Vincristine_.28BO.29|BO]] x 1, then [[#BEP_2|BEP]]; modified x 3
−
Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy:
 
−
*[[Cytarabine (Ara-C)]] 70 mg IT once on day 5 (in addition to doses above)
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 17 (in addition to dose above)
 
−
====Supportive therapy====
 
−
*[[Folinic acid (Leucovorin)]] 15 mg PO once on day 18, 24 hours after intrathecal [[Methotrexate (MTX)]]
 
−
====Supportive therapy====
 
−
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> IV every 3 hours for 5 doses on day 11, starting 36 hours after start of the day 10 methotrexate, then 15 mg/m<sup>2</sup> IV every 6 hours until methotrexate level is less than 50 nmol/L
 
−
*[[Folinic acid (Leucovorin)]] 15 mg PO once on day 16, 24 hours after intrathecal [[Methotrexate (MTX)]]
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/uL
 
−
*[[Allopurinol (Zyloprim)]] PO and/or [[Rasburicase (Elitek)]] prior to starting chemotherapy
 
−
'''3 cycles (see note)'''
 
−
''Note: Each cycle starts on the same day that the patient's ANC is greater than 1000/uL and unsupported (that is, without transfusion) platelet count greater than 75 x 10<sup>9</sup>/L.''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Mead GM, Barrans SL, Qian W, Walewski J, Radford JA, Wolf M, Clawson SM, Stenning SP, Yule CL, Jack AS; UK National Cancer Research Institute Lymphoma Clinical Studies Group; Australasian Leukaemia and Lymphoma Group. A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial). Blood. 2008 Sep 15;112(6):2248-60. Epub 2008 Jul 8. [http://www.bloodjournal.org/content/112/6/2248.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532802/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18612102 PubMed]
+
#'''EORTC 30948:''' Fosså SD, Paluchowska B, Horwich A, Kaiser G, de Mulder PH, Koriakine O, van Oosterom AT, de Prijck L, Collette L, de Wit R; [[Study_Groups#EORTC|EORTC]] GU Group. Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948). Br J Cancer. 2005 Nov 28;93(11):1209-14. [https://doi.org/10.1038/sj.bjc.6602830 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361516/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/16251877 PubMed]
−
==dmCODOX-M/IVAC - Modified Magrath {{#subobject:de3784|Regimen=1}}==
+
#'''MRC TE23:''' Huddart RA, Gabe R, Cafferty FH, Pollock P, White JD, Shamash J, Cullen MH, Stenning SP; TE23 Trial Management Group and Collaborators; National Cancer Research Institute Testis Cancer Clinical Studies Group. A randomised phase 2 trial of intensive induction chemotherapy (CBOP/BEP) and standard BEP in poor-prognosis germ cell tumours (MRC TE23, CRUK 05/014, ISRCTN 53643604). Eur Urol. 2015 Mar;67(3):534-43. Epub 2014 Jul 4. [https://www.europeanurology.com/article/S0302-2838(14)00608-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410298/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25001888 PubMed] ISRCTN53643604
−
dmCODOX-M/IVAC: '''<u>d</u>'''ose-'''<u>m</u>'''odified '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate alternating with '''<u>I</u>'''fosfamide, '''<u>V</u>'''epesid (etoposide), '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine)
+
==Cisplatin & Etoposide (EP) {{#subobject:b55260|Regimen=1}}==
 +
EP: '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin)
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:17f796|Variant=1}}===
+
===Regimen {{#subobject:ff4977|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 20%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! 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.1988.6.8.1231 Bosl et al. 1988]
 +
|1982-1986
 +
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 +
|[[Testicular_cancer_-_historical#VAB-6|VAB-6]]
 +
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532802/ Mead et al. 2008 (MRC/NCRI LY10)]
+
|[https://doi.org/10.1200/jco.1993.11.4.598 Bajorin et al. 1993]
−
|style="background-color:#91cf61"|Non-randomized
+
|1986-1990
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Etoposide_.28CE.29_99|CE]]
 +
| style="background-color:#91cf60" |Seems to have superior EFS
 
|-
 
|-
 
|}
 
|}
−
*Patients are stratified into high and low risk:
+
<div class="toccolours" style="background-color:#b3e2cd">
−
**Low risk patients must fulfill at least 3 of the following criteria:
+
====Chemotherapy====
−
***Normal LDH
+
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
−
***[[Performance_status#ECOG_performance_status_.28WHO.2FZubrod_score.29 | WHO performance status]] of 0 or 1
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
−
***Ann Arbor stage I or II
+
'''21-day cycle for 4 cycles'''
−
***0 or 1 extranodal sites of disease
 
−
**Any patients which do not meet low risk criteria are classified as high risk
 
−
''This regimen is for high-risk patients.''
 
−
====Chemotherapy, Part A: dmCODOX-M====
 
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8
 
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Methotrexate (MTX)]] by the following age-based criteria:
 
−
**Patients 65 years old or younger: 300 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 2700 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 3000 mg/m<sup>2</sup>)
 
−
**Patients older than 65 years old: 100 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 900 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 1000 mg/m<sup>2</sup>)
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 1 & 3
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 15
 
−
Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy:
 
−
*[[Cytarabine (Ara-C)]] 70 mg IT once on day 5 (in addition to doses above)
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 17 (in addition to dose above)
 
−
====Supportive therapy====
 
−
*[[Folinic acid (Leucovorin)]] 15 mg PO once on day 18, 24 hours after intrathecal [[Methotrexate (MTX)]]
 
−
====Supportive therapy====
 
−
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> IV every 3 hours for 5 doses on day 11, starting 36 hours after start of the day 10 methotrexate, then 15 mg/m<sup>2</sup> IV every 6 hours until methotrexate level is less than 50 nmol/L
 
−
*[[Folinic acid (Leucovorin)]] 15 mg PO once on day 16, 24 hours after intrathecal [[Methotrexate (MTX)]]
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/uL
 
−
*[[Allopurinol (Zyloprim)]] PO and/or [[Rasburicase (Elitek)]] prior to starting chemotherapy
 
−
====Chemotherapy, Part B: IVAC====
 
−
*[[Ifosfamide (Ifex)]] by the following age-based criteria:
 
−
**Patients 65 years old or younger: 1500 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
**Patients older than 65 years old: 1000 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
*[[Cytarabine (Ara-C)]] by the following age-based criteria:
 
−
**Patients 65 years old or younger: 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>)
 
−
**Patients older than 65 years old: 1000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 5
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] by the following age-based criteria:
 
−
**Patients 65 years old or younger: 300 mg/m<sup>2</sup> (mixed with [[Ifosfamide (Ifex)]]) IV over 60 minutes once per day on days 1 to 5, then 300 mg/m<sup>2</sup> IV every four hours for 2 doses on days 1 to 5
 
−
**Patients older than 65 years old: 200 mg/m<sup>2</sup> (mixed with [[Ifosfamide (Ifex)]]) IV over 60 minutes once per day on days 1 to 5, then 200 mg/m<sup>2</sup> IV every four hours for 2 doses on days 1 to 5
 
−
*[[Folinic acid (Leucovorin)]] 15 mg PO once on day 6, 24 hours after intrathecal [[Methotrexate (MTX)]]
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 7 and continuing until ANC greater than 1000/uL
 
−
'''4 cycles (see note)'''
 
−
''Note: dmCODOX-M and IVAC are given in an alternating fashion for a total of 4 cycles (A, B, A, B). Each cycle starts on the same day that the patient's ANC is greater than 1000/uL and unsupported (that is, without transfusion) platelet count greater than 75 x 10<sup>9</sup>/L.''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Mead GM, Barrans SL, Qian W, Walewski J, Radford JA, Wolf M, Clawson SM, Stenning SP, Yule CL, Jack AS; UK National Cancer Research Institute Lymphoma Clinical Studies Group; Australasian Leukaemia and Lymphoma Group. A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial). Blood. 2008 Sep 15;112(6):2248-60. Epub 2008 Jul 8. [http://www.bloodjournal.org/content/112/6/2248.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532802/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18612102 PubMed]
+
#Bosl GJ, Geller NL, Bajorin D, Leitner SP, Yagoda A, Golbey RB, Scher H, Vogelzang NJ, Auman J, Carey R, Fair WR, Herr H, Morse M, Sogani P, Whitmore W. A randomized trial of etoposide + cisplatin versus vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin in patients with good-prognosis germ cell tumors. J Clin Oncol. 1988 Aug;6(8):1231-8. [https://doi.org/10.1200/jco.1988.6.8.1231 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2457657 PubMed]
−
==EPOCH, dose-escalated {{#subobject:ded061|Regimen=1}}==
+
##'''Update:''' Xiao H, Mazumdar M, Bajorin DF, Sarosdy M, Vlamis V, Spicer J, Ferrara J, Bosl GJ, Motzer RJ. Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin. J Clin Oncol. 1997 Jul;15(7):2553-8. [https://doi.org/10.1200/jco.1997.15.7.2553 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9215824 PubMed]
−
EPOCH: '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin (Vincristine), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin)
+
#Bajorin DF, Sarosdy MF, Pfister DG, Mazumdar M, Motzer RJ, Scher HI, Geller NL, Fair WR, Herr H, Sogani P, Sheinfeld J, Russo P, Vlamis V, Carey R, Vogelzang NJ, Crawford ED, Bosl GJ. Randomized trial of etoposide and cisplatin versus etoposide and carboplatin in patients with good-risk germ cell tumors: a multiinstitutional study. J Clin Oncol. 1993 Apr;11(4):598-606. [https://doi.org/10.1200/jco.1993.11.4.598 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8386751 PubMed]
 +
##'''Update:''' Xiao H, Mazumdar M, Bajorin DF, Sarosdy M, Vlamis V, Spicer J, Ferrara J, Bosl GJ, Motzer RJ. Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin. J Clin Oncol. 1997 Jul;15(7):2553-8. [https://doi.org/10.1200/jco.1997.15.7.2553 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9215824 PubMed]
 +
#'''Retrospective:''' Kondagunta GV, Bacik J, Bajorin D, Dobrzynski D, Sheinfeld J, Motzer RJ, Bosl GJ. Etoposide and cisplatin chemotherapy for metastatic good-risk germ cell tumors. J Clin Oncol. 2005 Dec 20;23(36):9290-4. [https://doi.org/10.1200/jco.2005.03.6616 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16361627 PubMed]
 +
==M-TIP {{#subobject:f02838|Regimen=1}}==
 +
M-TIP: '''<u>M</u>'''ethotrexate, '''<u>T</u>'''axol (Paclitaxel), '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:e70b4b|Variant=1}}===
+
===Regimen {{#subobject:c25eca|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 25%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/101/12/4653.long Little et al. 2003]
+
|[https://doi.org/10.1016/j.urolonc.2008.10.013 Pectasides et al. 2008a]
−
|style="background-color:#91cf61"|Non-randomized
+
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
−
''Note: the paper refers to this regimen as dose-adjusted EPOCH but to avoid confusion with the other version of dose-adjusted EPOCH, we refer to it as dose-escalated EPOCH, here.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[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>)
+
*[[Methotrexate (MTX)]] 250 mg/m<sup>2</sup> IV over 4 hours once on day 1
−
*[[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>)
+
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] by the following laboratory-based criteria:
+
*[[Ifosfamide (Ifex)]] 1200 mg/m<sup>2</sup> IV over 120 minutes once per day on days 2 to 6
−
**CD4+ count less than 100/uL: 187 mg/m<sup>2</sup> IV over 15 minutes once on day 5
+
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 120 minutes once per day on days 2 to 6
−
**CD4+ count greater than 100/uL: 375 mg/m<sup>2</sup> IV over 15 minutes once on day 5
 
−
**In each subsequent cycle, increase dose by 187 mg/m<sup>2</sup> if the neutrophil nadir is greater than 500/uL and platelet nadir is greater than 25 x 10<sup>9</sup>/L. Decrease dose by 187 mg/m<sup>2</sup> if the neutrophil nadir is less than 500/uL or platelet nadir is less than 25 x 10<sup>9</sup>/L.
 
−
*[[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 once per day on days 1 to 5
 
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC greater than 5000/uL past nadir
+
*[[Folinic acid (Leucovorin)]]
−
'''21-day cycle for 6 cycles'''
+
'''4 cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Little RF, Pittaluga S, Grant N, Steinberg SM, Kavlick MF, Mitsuya H, Franchini G, Gutierrez M, Raffeld M, Jaffe ES, Shearer G, Yarchoan R, Wilson WH. Highly effective treatment of acquired immunodeficiency syndrome-related lymphoma with dose-adjusted EPOCH: impact of antiretroviral therapy suspension and tumor biology. Blood. 2003 Jun 15;101(12):4653-9. Epub 2003 Feb 27. [http://www.bloodjournal.org/content/101/12/4653.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12609827 PubMed]
+
#Pectasides D, Pectasides E, Papaxoinis G, Xiros N, Kamposioras K, Tountas N, Economopoulos T. Methotrexate, paclitaxel, ifosfamide, and cisplatin in poor-risk nonseminomatous germ cell tumors. Urol Oncol. 2010 Nov-Dec;28(6):617-23. Epub 2008 Dec 25. [https://doi.org/10.1016/j.urolonc.2008.10.013 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19110454 PubMed]
−
==GMALL-R {{#subobject:b6032d|Regimen=1}}==
+
==PVeBV {{#subobject:77c12b|Regimen=1}}==
−
GMALL-R: '''<u>G</u>'''erman '''<u>M</u>'''ulticenter Study Group for the Treatment of Adult '''<u>A</u>'''cute '''<u>L</u>'''ymphoblastic '''<u>L</u>'''eukemia, '''<u>R</u>'''ituximab
+
PVeBV: '''<u>P</u>'''latinol (Cisplatin), '''<u>Ve</u>'''lban (Vinblastine), '''<u>B</u>'''leomycin, '''<u>V</u>'''epesid (Etoposide)
 +
<br>VBEP: '''<u>V</u>'''inblastine, '''<u>B</u>'''leomycin, '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin)
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:2c9694|Variant=1}}===
+
===Regimen {{#subobject:4815f7|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 20%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! 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/10.1002/cncr.27918 Ribera et al. 2013 (Burkimab)]
+
|[https://www.karger.com/Article/Abstract/474596 Chevreau et al. 1993]
−
|style="background-color:#91cf61"|Phase 2
+
|NR in abstract
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#PVeBV_99|PVeBV]], then [[#PEC.2C_then_auto_HSCT_99|PEC with auto HSCT]]
 +
| style="background-color:#ffffbf" |Did not meet efficacy endpoints of CR rate/OS
 
|-
 
|-
 
|}
 
|}
−
''Numbering of days is based on prephase->A->B->C; however, certain patient populations received different ordering of regimen, see below.''
+
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy, prephase====
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
+
*[[Cisplatin (Platinol)]]
−
====Glucocorticoid therapy, prephase====
+
*[[Vinblastine (Velban)]]
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
+
*[[Bleomycin (Blenoxane)]]
−
====Targeted therapy, cycle A====
+
*[[Etoposide (Vepesid)]]
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 4 hours once on day 7
 
−
====Chemotherapy, cycle A====
 
−
*[[Vincristine (Oncovin)]] 2 mg IV bolus once on day 8
 
−
*[[Methotrexate (MTX)]] by the following age-based criteria:
 
−
**55 or younger: 1500 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 8
 
−
**Older than 55 years: 750 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 8
 
−
*[[Ifosfamide (Ifex)]] 800 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8 to 12
 
−
*[[Teniposide (Vumon)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 11 & 12
 
−
*[[Cytarabine (Ara-C)]] by the following age-based criteria:
 
−
**55 or younger: 150 mg/m<sup>2</sup> IV over 60 minutes twice per day on days 11 & 12
 
−
**Older than 55 years: 75 mg/m<sup>2</sup> IV over 60 minutes twice per day on days 11 & 12
 
−
====Glucocorticoid therapy, cycle A====
 
−
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV bolus once per day on days 8 to 12
 
−
====Supportive therapy, cycle A====
 
−
*[[Folinic acid (Leucovorin)]] (dose/route/schedule not specified), starting 12 hours after [[Methotrexate (MTX)]] infusion
 
−
====Targeted therapy, cycle B====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 4 hours once on day 28
 
−
====Chemotherapy, cycle B====
 
−
*[[Vincristine (Oncovin)]] 2 mg IV bolus once on day 29
 
−
*[[Methotrexate (MTX)]] by the following age-based criteria:
 
−
**55 or younger: 1500 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 29
 
−
**Older than 55 years: 750 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 29
 
−
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV over 60 minutes once per day on days 29 to 33
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 15 minutes once per day on days 32 & 33
 
−
====Glucocorticoid therapy, cycle B====
 
−
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV bolus once per day on days 29 to 33
 
−
====Supportive therapy, cycle B====
 
−
*[[Folinic acid (Leucovorin)]] (dose/route/schedule not specified), starting 12 hours after [[Methotrexate (MTX)]] infusion
 
−
====Targeted therapy, cycle C====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 4 hours once on day 49
 
−
====Chemotherapy, cycle C====
 
−
*[[Vindesine (Eldisine)]] 3 mg/m<sup>2</sup> (maximum dose of 5 mg) IV bolus once on day 50
 
−
*[[Methotrexate (MTX)]] by the following age-based criteria:
 
−
**55 or younger: 1500 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 50
 
−
**Older than 55 years: 750 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 50
 
−
*[[Etoposide (Vepesid)]] 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 53 & 54
 
−
*[[Cytarabine (Ara-C)]] by the following age-based criteria:
 
−
**55 or younger: 2000 mg/m<sup>2</sup> IV over 3 hours twice per day on day 54
 
−
**Older than 55 years: 1000 mg/m<sup>2</sup> IV over 3 hours twice per day on day 54
 
−
====Glucocorticoid therapy, cycle C====
 
−
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV bolus once per day on days 50 to 54
 
−
====Supportive therapy, cycle C====
 
−
*[[Folinic acid (Leucovorin)]] (dose/route/schedule not specified), starting 12 hours after [[Methotrexate (MTX)]] infusion
 
−
'''Give regimen as follows:'''
 
−
*'''Advanced stage and younger than 55 years: A->B->C x 2 courses (6 total cycles)'''
 
−
*'''Older than 55 years: Alternate A & B x 3 courses (6 total cycles)'''
 
−
*'''Localized stage: 4 total cycles (unclear from protocol if this means A alternating with B or A->B->C->A)'''
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] 15 mg IT once per day on days 1, 8, 12, 29, 33
 
−
*[[Cytarabine (Ara-C)]] 40 mg IT once per day on days 1, 8, 12, 29, 33
 
−
*[[Dexamethasone (Decadron)]] 20 mg IT once per day on days 1, 8, 12, 29, 33
 
−
'''8 doses total'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''Burkimab:''' Ribera JM, García O, Grande C, Esteve J, Oriol A, Bergua J, González-Campos J, Vall-Llovera F, Tormo M, Hernández-Rivas JM, García D, Brunet S, Alonso N, Barba P, Miralles P, Llorente A, Montesinos P, Moreno MJ, Hernández-Rivas JÁ, Bernal T. Dose-intensive chemotherapy including rituximab in Burkitt's leukemia or lymphoma regardless of human immunodeficiency virus infection status: final results of a phase 2 study (Burkimab). Cancer. 2013 May 1;119(9):1660-8. Epub 2013 Jan 29. [https://doi.org/10.1002/cncr.27918 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23361927 PubMed] NCT00388193
+
#Chevreau C, Droz JP, Pico JL, Biron P, Kerbrat P, Cure H, Héron JF, Chevallier B, Fargeot P, Kramar A, Bouzy J. Early intensified chemotherapy with autologous bone marrow transplantation in first line treatment of poor risk non-seminomatous germ cell tumours: preliminary results of a French randomized trial. Eur Urol. 1993;23(1):213-7. [https://www.karger.com/Article/Abstract/474596 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8386652 PubMed]
−
==m-BACOD {{#subobject:f471bb|Regimen=1}}==
+
##'''Update:''' Droz JP, Kramar A, Biron P, Pico JL, Kerbrat P, Pény J, Curé H, Chevreau C, Théodore C, Bouzy J, Culine S; Genito-Urinary Group of the French Federation of Cancer Centers. Failure of high-dose cyclophosphamide and etoposide combined with double-dose cisplatin and bone marrow support in patients with high-volume metastatic nonseminomatous germ-cell tumours: mature results of a randomised trial. Eur Urol. 2007 Mar;51(3):739-46. Epub 2006 Oct 27. [https://www.europeanurology.com/article/S0302-2838(06)01329-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17084512 PubMed]
−
m-BACOD: '''<u>m</u>'''ethotrexate (moderate dose), '''<u>B</u>'''leomycin, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>D</u>'''examethasone
+
==VIP {{#subobject:88c12b|Regimen=1}}==
 +
VIP: '''<u>V</u>'''epesid (Etoposide), '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, "low-dose" #1 {{#subobject:d60b9a|Variant=1}}===
+
===Regimen {{#subobject:4918f7|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 20%"|Study
+
! style="width: 20%" |Study
−
!style="width: 20%"|Years of enrollment
+
! style="width: 20%" |Years of enrollment
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 20%"|Comparator
+
! style="width: 20%" |Comparator
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1056/NEJM199706053362304 Kaplan et al. 1997 (ACTG 142)]
+
|[https://doi.org/10.1200/jco.1998.16.4.1287 Nichols et al. 1998 (ECOG E3887)]
−
|1991-1994
+
|1987-1992
−
|style="background-color:#1a9851"|Phase 3 (E-de-esc)
+
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
−
|[[#m-BACOD|m-BACOD]]; standard-dose
+
|[[#BEP_2|BEP]]
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
|-
 
|-
 
|}
 
|}
−
''Note: this is of historical interest, only.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Methotrexate (MTX)]] 200 mg/m<sup>2</sup> IV once on day 15
+
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 5
−
*[[Bleomycin (Blenoxane)]] 4 units/m<sup>2</sup> IV once on day 1
+
*[[Ifosfamide (Ifex)]] 1200 mg/m<sup>2</sup> IV once per day on days 1 to 5
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once on day 1
+
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Sargramostim (Leukine)]] 5 mcg/kg SC once per day on days 4 to 13 (as needed)
+
*[[Mesna (Mesnex)]] 120 mg/m<sup>2</sup> IV slow push once on day 1 '''given before [[Ifosfamide (Ifex)]]''', then 1200 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours (though not clearly specified in Nichols et al. 1998, based on its use with ifosfamide, it is assumed that the mesna dose was 1200 mg/m<sup>2</sup>/day)
−
====CNS therapy, prophylaxis====
+
*Normal saline 100 mL/hour IV over 12 hours once per day on days 1 to 5, prior to [[Cisplatin (Platinol)]]
−
*[[Cytarabine (Ara-C)]] as follows:
+
*Normal saline 100 mL/hour IV throughout the 5 day course of [[Cisplatin (Platinol)]], ending 6 hours after each cycle's last cisplatin dose
−
**Cycle 1: 50 mg IT once per day on days 1, 8, 15, 22
+
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 5 mcg/kg SC once per day on days 7 to 16
−
'''21-day cycle for 2 cycles past complete remission (minimum of 4 cycles)'''
+
'''21-day cycle for 4 cycles'''
−
</div></div><br>
+
</div></div>
 +
===References===
 +
#'''ECOG E3887:''' Nichols CR, Catalano PJ, Crawford ED, Vogelzang NJ, Einhorn LH, Loehrer PJ. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol. 1998 Apr;16(4):1287-93. [https://doi.org/10.1200/jco.1998.16.4.1287 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9552027 PubMed]
 +
##'''Update:''' Hinton S, Catalano PJ, Einhorn LH, Nichols CR, David Crawford E, Vogelzang N, Trump D, Loehrer PJ Sr. Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors: final analysis of an intergroup trial. Cancer. 2003 Apr 15;97(8):1869-75. [https://doi.org/full/10.1002/cncr.11271 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12673712 PubMed]
 +
=Relapsed or refractory, salvage therapy=
 +
==Carboplatin & Etoposide (CE), then auto HSCT {{#subobject:defcbf|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, "low-dose" #2 {{#subobject:d20b9a|Variant=1}}===
+
===Regimen {{#subobject:8d59e2|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 25%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://jamanetwork.com/journals/jama/article-abstract/386383 Levine et al. 1991]
+
|[https://doi.org/10.1200/jco.1989.7.7.932 Nichols et al. 1989]
−
| style="background-color:#91cf61" |Non-randomized
+
| style="background-color:#91cf61" |Phase 1/2
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa067749 Einhorn et al. 2007a]
 +
| style="background-color:#ffffbe" |Retrospective
 
|-
 
|-
 
|}
 
|}
−
''Note: this is of historical interest, only; the MTX dose is slightly higher than above.''
+
''Note: the doses here are the ones from the retrospective NEJM article, not from the prospective phase I/II trial. Some patients had salvage [[#VeIP|VeIP]] prior to high-dose therapy; others proceeded directly with this regimen as their first salvage treatment.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Methotrexate (MTX)]] 500 mg/m<sup>2</sup> IV once on day 15
+
*[[Carboplatin (Paraplatin)]] 700 mg/m<sup>2</sup> IV once per day on days -5, -4, -3
−
*[[Bleomycin (Blenoxane)]] 4 units/m<sup>2</sup> IV once on day 1
+
*[[Etoposide (Vepesid)]] 750 mg/m<sup>2</sup> IV once per day on days -5, -4, -3
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once on day 1
+
*At least 1 million CD34+ cells per kilogram of body weight was needed for each cycle of chemotherapy.
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV once on day 1
+
'''2 cycles, with the second cycle starting after "recovery of granulocyte and platelet counts"'''
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
+
</div>
−
====Glucocorticoid therapy====
+
<div class="toccolours" style="background-color:#cbd5e7">
−
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
====Subsequent treatment====
−
====Supportive therapy====
+
*"Most patients" who had CR/PR after two cycles of therapy received [[#Etoposide_monotherapy|etoposide]] consolidation
−
*[[Folinic acid (Leucovorin)]]
+
</div></div>
−
====CNS therapy, prophylaxis====
+
===References===
−
*[[Cytarabine (Ara-C)]] 50 mg IT once per day on days 1, 8, 21, 28
+
#Nichols CR, Tricot G, Williams SD, van Besien K, Loehrer PJ, Roth BJ, Akard L, Hoffman R, Goulet R, Wolff SN, Giannone L, Greer J, Einhorn LH, Jansen J. Dose-intensive chemotherapy in refractory germ cell cancer--a phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation. J Clin Oncol. 1989 Jul;7(7):932-9. [https://doi.org/10.1200/jco.1989.7.7.932 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2544687 PubMed]
−
'''4 to 6 cycles'''
+
#'''Retrospective:''' Einhorn LH, Williams SD, Chamness A, Brames MJ, Perkins SM, Abonour R. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med. 2007 Jul 26;357(4):340-8. [https://doi.org/10.1056/NEJMoa067749 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17652649 PubMed]
−
</div></div><br>
+
==Cisplatin & Epirubicin {{#subobject:562595|Regimen=1}}==
 +
CIS-EPI: '''<u>CIS</u>'''platin, '''<u>EPI</u>'''rubicin
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #3, "standard-dose" {{#subobject:8d9222|Variant=1}}===
+
===Regimen {{#subobject:7ba115|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 20%"|Study
+
! style="width: 25%" |Study
−
!style="width: 20%"|Years of enrollment
+
! style="width: 25%" |[[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/NEJM199706053362304 Kaplan et al. 1997 (ACTG 142)]
+
|[https://doi.org/10.1200/jco.2006.05.8065 Bedano et al. 2006]
−
|1991-1994
+
| style="background-color:#91cf61" |Phase 2
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#m-BACOD|m-BACOD]]; low-dose
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
 
|-
 
|-
 
|}
 
|}
−
''Note: this is of historical interest, only.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Methotrexate (MTX)]] 200 mg/m<sup>2</sup> IV once on day 15
+
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
−
*[[Bleomycin (Blenoxane)]] 4 units/m<sup>2</sup> IV once on day 1
+
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV over 15 to 30 minutes once on day 1
−
*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 6 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Sargramostim (Leukine)]] 5 mcg/kg SC once per day on days 4 to 13
+
*WBC support with ONE of the following:
−
====CNS therapy, prophylaxis====
+
**[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 7 to 16
−
*[[Cytarabine (Ara-C)]] as follows:
+
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once on either day 6 or 7
−
**Cycle 1: 50 mg IT once per day on days 1, 8, 15, 22
+
'''21-day cycle for up to 4 cycles'''
−
'''21-day cycle for 2 cycles past complete remission (minimum of 4 cycles)'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Levine AM, Wernz JC, Kaplan L, Rodman N, Cohen P, Metroka C, Bennett JM, Rarick MU, Walsh C, Kahn J, Miles S, Ehmann WC, Feinberg J, Nathwani B, Gill PS, Mitsuyasu R. Low-dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance in AIDS-related lymphoma: a prospective multi-institutional trial. JAMA. 1991 Jul 3;266(1):84-8. [https://jamanetwork.com/journals/jama/article-abstract/386383 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1710673 PubMed]
+
#Bedano PM, Brames MJ, Williams SD, Juliar BE, Einhorn LH. Phase II study of cisplatin plus epirubicin salvage chemotherapy in refractory germ cell tumors. J Clin Oncol. 2006 Dec 1;24(34):5403-7. [https://doi.org/10.1200/jco.2006.05.8065 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17135640 PubMed]
−
# '''ACTG 142:''' Kaplan LD, Straus DJ, Testa MA, Von Roenn J, Dezube BJ, Cooley TP, Herndier B, Northfelt DW, Huang J, Tulpule A, Levine AM; National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. N Engl J Med. 1997 Jun 5;336(23):1641-8. [https://doi.org/10.1056/NEJM199706053362304 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9171066 PubMed]
+
==GIP {{#subobject:118eb4|Regimen=1}}==
−
==R-CDOP {{#subobject:ec091e|Regimen=1}}==
+
GIP: '''<u>G</u>'''emcitabine, '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
−
R-CDOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''oxil (Pegylated liposomal doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
−
<br>DR-COP: '''<u>D</u>'''oxil (pegylated liposomal doxorubicin), '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:de2769|Variant=1}}===
+
===Regimen {{#subobject:a138e6|Variant=1}}===
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
+
{| class="wikitable" style="width: 60%; text-align:center;"  
−
!style="width: 33%"|Study
+
! style="width: 33%" |Study
−
!style="width: 33%"|Years of enrollment
+
! style="width: 33%" |Years of enrollment
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530691/ Levine et al. 2012 (AMC047)]
+
|[https://doi.org/10.1093/annonc/mdu099 Fizazi et al. 2014 (GIP-TG)]
−
|2007-NR
+
|2004-2009
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+
*[[Gemcitabine (Gemzar)]]
−
*[[Pegylated liposomal doxorubicin (Doxil)]] 40 mg/m<sup>2</sup> IV once on day 1
+
*[[Ifosfamide (Ifex)]]
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
*[[Cisplatin (Platinol)]]
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
====CNS therapy, prophylaxis====
 
−
*"CNS prophylaxis was mandated in patients with involvement of bone marrow, testis, sinuses, or epidural regions and with stage IV and/or at least two extranodal sites, with specific regimen left to physician discretion."
 
−
*Highly Active Antiretroviral Therapy (HAART) required; specific regimen left to physician discretion. Use of zidovudine was not allowed.
 
−
====Supportive therapy====
 
−
*G-CSF prophylaxis, starting on day 3 and continuing until beyond nadir of blood counts, with one of the following:
 
−
**[[Filgrastim (Neupogen)]]
 
−
**[[Pegfilgrastim (Neulasta)]]
 
−
**[[Sargramostim (Leukine)]]
 
−
*Erythropoietin (e.g. [[Epoetin alfa (Procrit)]] or [[Darbepoetin alfa (Aranesp)]]) at physician discretion
 
−
*[[:Category:PCP_prophylaxis|PCP prophylaxis]] required
 
−
*Oral [[:Category:Fluoroquinolone|fluoroquinolone]] if CD4 cell count less than or equal to 100 and ANC less than 500/uL at entry or during treatment
 
−
'''21- to 28-day cycle for up to 6 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''AMC047:''' Levine AM, Noy A, Lee JY, Tam W, Ramos JC, Henry DH, Parekh S, Reid EG, Mitsuyasu R, Cooley T, Dezube BJ, Ratner L, Cesarman E, Tulpule A. Pegylated liposomal doxorubicin, rituximab, cyclophosphamide, vincristine, and prednisone in AIDS-related lymphoma: AIDS Malignancy Consortium study 047. J Clin Oncol. 2013 Jan 1;31(1):58-64. Epub 2012 Nov 19. [https://doi.org/10.1200/jco.2012.42.4648 link to original article]  '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530691/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23169503 PubMed] NCT00389818
+
#'''GIP-TG:''' Fizazi K, Gravis G, Flechon A, Geoffrois L, Chevreau C, Laguerre B, Delva R, Eymard JC, Rolland F, Houede N, Laplanche A, Burcoveanu D, Culine S. Combining gemcitabine, cisplatin, and ifosfamide (GIP) is active in patients with relapsed metastatic germ-cell tumors (GCT): a prospective multicenter GETUG phase II trial. Ann Oncol. 2014 May;25(5):987-91. Epub 2014 Mar 4. [https://doi.org/10.1093/annonc/mdu099 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24595454 PubMed] NCT00127049
−
==R-CHOP {{#subobject:973922|Regimen=1}}==
+
==Ifosfamide & Paclitaxel {{#subobject:328eb4|Regimen=1}}==
−
R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
+
TI: '''<u>T</u>'''axol (Paclitaxel) & '''<u>I</u>'''fosfamide
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, 3 cycles {{#subobject:bbe63d|Variant=1}}===
+
===Regimen {{#subobject:39c8e6|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 20%"|Study
+
! style="width: 25%" |Study
−
!style="width: 20%"|Years of enrollment
+
! style="width: 25%" |[[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://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ Kaplan et al. 2005 (AMC010)]
+
|[https://doi.org/10.1200/jco.2006.06.9401 Kondagunta et al. 2007]
−
|1998-2002
+
| style="background-color:#91cf61" |Phase 2
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[#CHOP|CHOP]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate
 
 
|-
 
|-
 
|}
 
|}
−
''Intended for patients with stage I, IE, or nonbulky stage II disease.''
+
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day -2
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
*[[Ifosfamide (Ifex)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 2 to 4
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
 
====Supportive therapy====
 
====Supportive therapy====
−
*Combination antiretrovirals were required
+
*[[Mesna (Mesnex)]] with [[Ifosfamide (Ifex)]] on days 2 to 4 (no further details given)
−
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 5 mcg/kg SC once per day from days 4 to 13 or until ANC greater than 10k/uL.
+
'''14-day cycle for 2 cycles; leukapheresis on days 11 to 13 (done on cycle 1, and then only if needed on cycle 2 to have at least 6 x 10<sup>6</sup> CD34+ cells/kg body weight in peripheral blood stem cells)'''
−
*PCP prophylaxis with ONE of the following:
 
−
**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] (dose/schedule not specified)
 
−
**[[Dapsone (Aczone)]] (dose/schedule not specified)
 
−
**[[Pentamidine (Nebupent)]] (dose/schedule not specified)
 
−
'''21-day cycle for 3 cycles for early disease, or minimum of 6 cycles or 2 past CR for advanced disease'''
 
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#cbd5e7">
 
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*[[#Radiation_therapy|IFRT]] x 40 Gy
+
*[[#Carboplatin_.26_Etoposide_.28CE.29.2C_then_auto_HSCT_2|CE with auto HSCT]]
 +
</div></div>
 +
===References===
 +
#Kondagunta GV, Bacik J, Sheinfeld J, Bajorin D, Bains M, Reich L, Deluca J, Budnick A, Ishill N, Mazumdar M, Bosl GJ, Motzer RJ. Paclitaxel plus Ifosfamide followed by high-dose carboplatin plus etoposide in previously treated germ cell tumors. J Clin Oncol. 2007 Jan 1;25(1):85-90. Erratum in: J Clin Oncol. 2007 May 20;25(15):2149. [https://doi.org/10.1200/jco.2006.06.9401 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17194908 PubMed]
 +
##'''Update:''' Feldman DR, Sheinfeld J, Bajorin DF, Fischer P, Turkula S, Ishill N, Patil S, Bains M, Reich LM, Bosl GJ, Motzer RJ. TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis. J Clin Oncol. 2010 Apr 1;28(10):1706-13. Epub 2010 Mar 1. Erratum in: J Clin Oncol. 2010 Dec 1;28(34):5126. [https://doi.org/10.1200/JCO.2009.25.1561 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651604/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20194867 PubMed]
 +
==TIP {{#subobject:52d2ea|Regimen=1}}==
 +
TIP: '''<u>T</u>'''axol (Paclitaxel), '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 175/6000/100 {{#subobject:egc70a|Variant=1}}===
 +
{| class="wikitable" style="width: 40%; text-align:center;"
 +
! style="width: 25%" |Study
 +
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282876/ Kurobe et al. 2014]
 +
| style="background-color:#91cf61" |Phase 2
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 +
*[[Ifosfamide (Ifex)]] 1200 mg/m<sup>2</sup> IV over 120 minutes once per day on days 2 to 6
 +
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 120 minutes once per day on days 2 to 6
 +
====Supportive therapy====
 +
*[[Mesna (Mesnex)]] by the following split schedule:
 +
**240 mg/m<sup>2</sup> IV once per day on days 2 to 6, prior to each dose of [[Ifosfamide (Ifex)]]
 +
**240 mg/m<sup>2</sup> IV once per day on days 2 to 6; 4 hours after each dose of [[Ifosfamide (Ifex)]]
 +
**240 mg/m<sup>2</sup> IV once per day on days 2 to 6; 8 hours after each dose of [[Ifosfamide (Ifex)]]
 +
'''21-day cycle for 4 cycles'''
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, prednisone 40 mg/m<sup>2</sup> {{#subobject:c5fd4a|Variant=1}}===
+
===Regimen variant #2, 250/6000/100 {{#subobject:cda70a|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 25%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2005.19.638 Kondagunta et al. 2005]
 +
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2005.05.4684 Boué et al. 2006]
+
|}
−
|style="background-color:#91cf61"|Phase 2
+
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Paclitaxel (Taxol)]] 250 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 +
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV over 60 minutes once per day on days 2 to 5
 +
*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV over 30 minutes once per day on days 2 to 5
 +
====Supportive therapy====
 +
*[[Mesna (Mesnex)]] by the following split schedule:
 +
**500 mg/m<sup>2</sup> IV once per day on days 2 to 5, prior to each dose of [[Ifosfamide (Ifex)]]
 +
**500 mg/m<sup>2</sup> IV once per day on days 2 to 5; 4 hours after each dose of [[Ifosfamide (Ifex)]]
 +
**500 mg/m<sup>2</sup> IV once per day on days 2 to 5; 8 hours after each dose of [[Ifosfamide (Ifex)]]
 +
*[[Dexamethasone (Decadron)]] 20 mg PO twice on day 1; 14 and 7 hours prior to [[Paclitaxel (Taxol)]]
 +
*[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 60 minutes prior to [[Paclitaxel (Taxol)]]
 +
*[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 60 minutes prior to [[Paclitaxel (Taxol)]]
 +
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 7 to 18, discontinued if WBC greater than 10 x 10<sup>9</sup>/L for 2 days
 +
'''21-day cycle for 4 cycles'''
 +
</div></div>
 +
===References===
 +
#Kondagunta GV, Bacik J, Donadio A, Bajorin D, Marion S, Sheinfeld J, Bosl GJ, Motzer RJ. Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. J Clin Oncol. 2005 Sep 20;23(27):6549-55. [https://doi.org/10.1200/jco.2005.19.638 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16170162 PubMed]
 +
#Kurobe M, Kawai K, Oikawa T, Ichioka D, Kandori S, Takaoka E, Kojima T, Joraku A, Suetomi T, Miyazaki J, Nishiyama H. Paclitaxel, ifosfamide, and cisplatin (TIP) as salvage and consolidation chemotherapy for advanced germ cell tumor. J Cancer Res Clin Oncol. 2015 Jan;141(1):127-33. Epub 2014 Jul 26. [https://doi.org/10.1007/s00432-014-1760-x link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282876/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25062721 PubMed]
 +
#'''Alliance A031102:''' NCT02375204
 +
==VeIP {{#subobject:836545|Regimen=1}}==
 +
VeIP: '''<u>Ve</u>'''lban (Vinblastine), '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:1275b4|Variant=1}}===
 +
{| class="wikitable" style="width: 60%; text-align:center;"
 +
! style="width: 33%" |Study
 +
! style="width: 33%" |Years of enrollment
 +
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1111/j.1365-2141.2007.06943.x Ribera et al. 2007x]
+
|[https://annals.org/aim/article-abstract/702620/salvage-therapy-recurrent-germ-cell-cancer-ifosfamide-cisplatin-plus-either Loehrer et al. 1988]
−
|style="background-color:#91cf61"|Phase 2
+
|1983-1986
 +
| style="background-color:#91cf61" |Phase 2 (RT)
 +
|-
 +
|[https://doi.org/10.1200/jco.1998.16.7.2500 Loehrer et al. 1998]
 +
|1984-1989
 +
| style="background-color:#91cf61" |Phase 2
 +
|-
 +
|}
 +
''Patients in Loehrer et al. 1998 had previously received cisplatin & etoposide based combination chemotherapy.''
 +
====Chemotherapy====
 +
*[[Vinblastine (Velban)]] 0.11 mg/kg IV once per day on days 1 & 2
 +
*[[Ifosfamide (Ifex)]] 1200 mg/m<sup>2</sup> IV once per day on days 1 to 5
 +
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 +
====Supportive therapy====
 +
*[[Mesna (Mesnex)]] 400 mg/m<sup>2</sup> IV bolus on day 1 prior to first dose of [[Ifosfamide (Ifex)]], then 1200 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours (total dose per cycle: 6400 mg/m<sup>2</sup>)
 +
*Normal saline 100 mL/hour IV continuous infusion over 120 hours, started on day 1
 +
'''21-day cycle for 4 cycles'''
 +
</div></div>
 +
===References===
 +
#Loehrer PJ Sr, Lauer R, Roth BJ, Williams SD, Kalasinski LA, Einhorn LH. Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Intern Med. 1988 Oct 1;109(7):540-6. [https://annals.org/aim/article-abstract/702620/salvage-therapy-recurrent-germ-cell-cancer-ifosfamide-cisplatin-plus-either link to original article] [https://pubmed.ncbi.nlm.nih.gov/2844110 PubMed]
 +
#Loehrer PJ Sr, Gonin R, Nichols CR, Weathers T, Einhorn LH. Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor. J Clin Oncol. 1998 Jul;16(7):2500-4. [https://doi.org/10.1200/jco.1998.16.7.2500 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9667270 PubMed]
 +
==VIP {{#subobject:de93dc|Regimen=1}}==
 +
VIP: '''<u>V</u>'''epesid (Etoposide), '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
 +
<br>PEI: '''<u>P</u>'''latinol (Cisplatin), '''<u>E</u>'''toposide, '''<u>I</u>'''fosfamide
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 1 cycle {{#subobject:e65d06|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! 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.2006.09.2148 Lorch et al. 2007]
 +
|1999-2004
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#VIP_2|VIP]] x 3, then [[#CEC.2C_then_auto_HSCT_99|CEC with auto HSCT]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS12
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
**In Boué et al. 2006, first dose was given on day -1
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+
*[[Etoposide (Vepesid)]]
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
*[[Ifosfamide (Ifex)]]
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
*[[Cisplatin (Platinol)]]
−
====Glucocorticoid therapy====
+
'''One course'''
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====CNS therapy, prophylaxis====
 
−
*Rivera et al. 2007x: ''To be given with each cycle; day of administration not reported.''
 
−
*[[Methotrexate (MTX)]] 12 mg IT
 
−
*[[Cytarabine (Ara-C)]] 40 mg IT
 
−
*[[Hydrocortisone (Cortef)]] 20 mg IT
 
−
====Supportive therapy====
 
−
*Combination antiretrovirals were required: one or two protease inhibitors and two nucleoside reverse transcriptase inhibitors
 
−
*PCP prophylaxis with ONE of the following:
 
−
**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] 160/800 mg PO TIW
 
−
**[[Pentamidine (Nebupent)]] 300 mg inhaled (schedule not specified)
 
−
'''21-day cycle for 6 cycles'''
 
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#cbd5e7">
 
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*Rivera et al. 2007x, patients with bulky disease or a residual mass: [[#Radiation_therapy|IFRT]] (details not provided)
+
*[[#Carboplatin_.26_Etoposide_.28CE.29.2C_then_auto_HSCT_2|CE, then auto HSCT]] x 3
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #3, prednisone 100 mg {{#subobject:b2deae|Variant=1}}===
+
===Regimen variant #2, 4 cycles {{#subobject:e6ac16|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 20%"|Study
+
! style="width: 20%" |Study
−
!style="width: 20%"|Years of enrollment
+
! style="width: 20%" |Years of enrollment
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 20%"|Comparator
+
! style="width: 20%" |Comparator
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/jco.1986.4.4.528 Loehrer et al. 1986]
 +
|1983-1984
 +
| style="background-color:#91cf61" |Non-randomized (RT)
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ Kaplan et al. 2005 (AMC010)]
+
|[https://doi.org/10.1093/annonc/mdi228 Pico et al. 2005 (IT 94)]
−
|1998-2002
+
|1994-2001
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
+
| style="background-color:#1a9851" |Phase 3 (C)
−
|[[#CHOP|CHOP]]
+
|[[#VIP_2|VIP]] x 3, then [[#CarboPEC.2C_then_auto_HSCT_99|CarboPEC with auto HSCT]]
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
|-
 
|-
 
|}
 
|}
−
''Intended for patients with advanced disease.''
+
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day -2
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+
*[[Etoposide (Vepesid)]]
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
*[[Ifosfamide (Ifex)]]
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
*[[Cisplatin (Platinol)]]
−
====Glucocorticoid therapy====
+
'''4 cycles'''
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*Combination antiretrovirals were required
 
−
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 5 mcg/kg SC once per day from days 4 to 13 or until ANC greater than 10k/uL.
 
−
*PCP prophylaxis with ONE of the following:
 
−
**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] (dose/schedule not specified)
 
−
**[[Dapsone (Aczone)]] (dose/schedule not specified)
 
−
**[[Pentamidine (Nebupent)]] (dose/schedule not specified)
 
−
'''21-day cycle for a minimum of 6 cycles or 2 past CR'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Partial or complete responders: [[#Rituximab_monotherapy|Rituximab]] maintenance
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''AMC010:''' Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. [http://www.bloodjournal.org/content/106/5/1538.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15914552 PubMed] NCT00003595
+
#Loehrer PJ Sr, Einhorn LH, Williams SD. VP-16 plus ifosfamide plus cisplatin as salvage therapy in refractory germ cell cancer. J Clin Oncol. 1986 Apr;4(4):528-36. [https://doi.org/10.1200/jco.1986.4.4.528 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3633952/ PubMed]
−
# Boué F, Gabarre J, Gisselbrecht C, Reynes J, Cheret A, Bonnet F, Billaud E, Raphael M, Lancar R, Costagliola D. Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin's lymphoma. J Clin Oncol. 2006 Sep 1;24(25):4123-8. Epub 2006 Aug 8. [https://doi.org/10.1200/jco.2005.05.4684 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16896005 PubMed]  
+
#'''IT 94:''' Pico JL, Rosti G, Kramar A, Wandt H, Koza V, Salvioni R, Theodore C, Lelli G, Siegert W, Horwich A, Marangolo M, Linkesch W, Pizzocaro G, Schmoll HJ, Bouzy J, Droz JP, Biron P; Genito-Urinary Group of the French Federation of Cancer Centers; EBMT. A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours. Ann Oncol. 2005 Jul;16(7):1152-9. Epub 2005 May 31. [https://doi.org/10.1093/annonc/mdi228 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15928070 PubMed]
−
# Ribera JM, Oriol A, Morgades M, González-Barca E, Miralles P, López-Guillermo A, Gardella S, López A, Abella E, García M; PETHEMA; GELTAMO; GELCAB; GESIDA. Safety and efficacy of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab in patients with human immunodeficiency virus-associated diffuse large B-cell lymphoma: results of a phase II trial. Br J Haematol. 2008 Feb;140(4):411-9. Epub 2007 Dec 19. [https://doi.org/10.1111/j.1365-2141.2007.06943.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18162120 PubMed]
+
#Lorch A, Kollmannsberger C, Hartmann JT, Metzner B, Schmidt-Wolf IG, Berdel WE, Weissinger F, Schleicher J, Egerer G, Haas A, Schirren R, Beyer J, Bokemeyer C, Rick O; German Testicular Cancer Study Group. Single versus sequential high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: a prospective randomized multicenter trial of the German Testicular Cancer Study Group. J Clin Oncol. 2007 Jul 1;25(19):2778-84. [https://doi.org/10.1200/JCO.2006.09.2148 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17602082 PubMed]
−
==R-CODOX-M {{#subobject:2c9b53|Regimen=1}}==
+
##'''Update:''' Lorch A, Kleinhans A, Kramar A, Kollmannsberger CK, Hartmann JT, Bokemeyer C, Rick O, Beyer J. Sequential versus single high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: long-term results of a prospective randomized trial. J Clin Oncol. 2012 Mar 10;30(8):800-5. Epub 2012 Jan 30. [https://doi.org/10.1200/JCO.2011.38.6391 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22291076 PubMed]
−
R-CODOX-M: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate
+
=Consolidation after salvage therapy=
 +
==Carboplatin & Etoposide (CE), then auto HSCT {{#subobject:328eb4|Regimen=1}}==
 +
TI-CE: '''<u>T</u>'''axol (Paclitaxel), '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:b34341|Variant=1}}===
+
===Regimen {{#subobject:39c8e6|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 25%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497960/ Noy et al. 2015 (AMC 048)]
+
|[https://doi.org/10.1200/jco.2006.06.9401 Kondagunta et al. 2007]
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
−
''Intended for '''low-risk''' HIV-associated Burkitt lymphoma, and the first published prospective regimen to explicitly use rituximab. This is sometimes called modified Magrath but is in fact a second modification to the modified Magrath described by [https://doi.org/10.1080/1042819031000141301 LaCasce et al. 2004].''
+
<div class="toccolours" style="background-color:#cbd5e8">
−
====Targeted therapy====
+
====Preceding treatment====
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+
*[[#Ifosfamide_.26_Paclitaxel|TI]] x 2
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once per day on days 1 & 2
+
*[[Carboplatin (Paraplatin)]] AUC 7 to 8 IV over 20 to 60 minutes once per day on days 1 to 3
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8
+
*[[Etoposide (Vepesid)]] 400 mg/m<sup>2</sup> IV once per day on days 1 to 3
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once on day 15
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] 50 mg IT once on day 1
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 1
 
−
*[[Hydrocortisone (Cortef)]] 50 mg IT once on day 1
 
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once 24 hours after methotrexate, then 25 mg/m<sup>2</sup> IV every 6 hours until methotrexate level is less than 50 nmol/L
+
*Peripheral blood stem cell support (at least 2 x 10<sup>6</sup> CD34+ cells/kg body weight per infusion) on day 5, 48 hours after carboplatin & etoposide (stem cells were infused each cycle)
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 3
+
'''14- to 21-day cycle for 3 cycles'''
−
*[[Filgrastim (Neupogen)]] (dose not specified) SC once per day, starting once methotrexate level is less than 50 nmol/L (approximately day 18) and continuing until ANC greater than 1000/uL
 
−
'''21- to 28-day cycle for 3 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Lacasce A, Howard O, Lib S, Fisher D, Weng A, Neuberg D, Shipp M. Modified Magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma. 2004 Apr;45(4):761-7. [https://doi.org/10.1080/1042819031000141301 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15160953 PubMed]
+
#Kondagunta GV, Bacik J, Sheinfeld J, Bajorin D, Bains M, Reich L, Deluca J, Budnick A, Ishill N, Mazumdar M, Bosl GJ, Motzer RJ. Paclitaxel plus Ifosfamide followed by high-dose carboplatin plus etoposide in previously treated germ cell tumors. J Clin Oncol. 2007 Jan 1;25(1):85-90. Erratum in: J Clin Oncol. 2007 May 20;25(15):2149. [https://doi.org/10.1200/jco.2006.06.9401 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17194908 PubMed]
−
# '''Retrospective:''' Barnes JA, Lacasce AS, Feng Y, Toomey CE, Neuberg D, Michaelson JS, Hochberg EP, Abramson JS. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: a retrospective analysis. Ann Oncol. 2011 Aug;22(8):1859-64. Epub 2011 Feb 21. [https://doi.org/10.1093/annonc/mdq677 link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/21339382 PubMed] content property of [http://hemonc.org HemOnc.org]
+
==Etoposide monotherapy {{#subobject:27e630|Regimen=1}}==
−
# '''Retrospective:''' Kassam S, Bower M, Lee SM, de Vos J, Fields P, Gandhi S, Nelson M, Montoto S, Tenant-Flowers M, Burns F, Marcus R, Edwards SG, Cwynarski K. A retrospective, multi-center analysis of treatment intensification for HIV-positive patients with high-risk diffuse large B-cell lymphoma. Leuk Lymphoma. 2013 Sep;54(9):1921-7. Epub 2013 Jan 4. [https://doi.org/10.3109/10428194.2012.754024 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23206228 PubMed]
 
−
# '''AMC 048:''' Noy A, Lee JY, Cesarman E, Ambinder R, Baiocchi R, Reid E, Ratner L, Wagner-Johnston N, Kaplan L. AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Blood. 2015 Jul 9;126(2):160-6. Epub 2015 May 8. [http://www.bloodjournal.org/content/126/2/160 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497960/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25957391 PubMed] NCT00392834
 
−
==R-CODOX-M/R-IVAC {{#subobject:9268b2|Regimen=1}}==
 
−
R-CODOX-M/R-IVAC: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate alternating with '''<u>R</u>'''ituximab, '''<u>I</u>'''fosfamide, '''<u>V</u>'''epesid (Etoposide), '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:7a0131|Variant=1}}===
+
===Regimen {{#subobject:d6089b|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 25%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1080/1042819031000141301 LaCasce et al. 2004]
+
|[https://doi.org/10.1200/jco.1989.7.7.932 Nichols et al. 1989]
−
| style="background-color:#ffffbe" |Phase 2, <20 pts
+
| style="background-color:#91cf61" |Phase 1/2
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497960/ Noy et al. 2015 (AMC 048)]
+
|[https://doi.org/10.1056/NEJMoa067749 Einhorn et al. 2007a]
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#ffffbe" |Retrospective
 
|-
 
|-
 
|}
 
|}
−
''Intended for '''high-risk''' HIV-associated Burkitt lymphoma, and the first published prospective regimen to explicitly use rituximab. This is sometimes called modified Magrath but is in fact a second modification to the modified Magrath described in LaCasce et al. 2004. Note that the preferred sequence is A, B, A, B but the authors note that for patients with anasarca or other concerns for retaining MTX, the sequence can be B, A, B, A. Also note that the paper does not specify whether hydrocortisone is used with the day 3 IT chemo; the authors have clarified (December 31, 2017) that this is left to institutional policy.''
+
<div class="toccolours" style="background-color:#cbd5e8">
−
====Targeted therapy====
+
====Preceding treatment====
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+
*[[#Carboplatin_.26_Etoposide_.28CE.29.2C_then_auto_HSCT|CE with auto HSCT]]
−
====Chemotherapy, part A (CODOX-M)====
+
</div>
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
+
<div class="toccolours" style="background-color:#b3e2cd">
−
**Cycles 1 & 3: 800 mg/m<sup>2</sup> IV once per day on days 1 & 2
+
====Chemotherapy====
−
*[[Vincristine (Oncovin)]] as follows:
+
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 21
−
**Cycles 1 & 3: 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8
+
'''28-day cycle for 3 cycles'''
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 & 3: 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 1 & 3: 3000 mg/m<sup>2</sup> IV once on day 15
 
−
====Supportive therapy, part A (CODOX-M)====
 
−
*[[Folinic acid (Leucovorin)]] as follows:
 
−
**Cycles 1 & 3: 200 mg/m<sup>2</sup> IV once 24 hours after methotrexate, then 25 mg/m<sup>2</sup> IV every 6 hours until methotrexate level is less than 50 nmol/L
 
−
*[[Filgrastim (Neupogen)]] as follows:
 
−
**Cycles 1 & 3: (dose not specified) SC once per day, starting once methotrexate level is less than 50 nmol/L (approximately day 18) and continuing until ANC greater than 1000/uL
 
−
====Chemotherapy, part B (IVAC)====
 
−
*[[Ifosfamide (Ifex)]] as follows:
 
−
**Cycles 2 & 4: 1500 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 7500 mg/m<sup>2</sup>)
 
−
*[[Etoposide (Vepesid)]] as follows:
 
−
**Cycles 2 & 4: 60 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 300 mg/m<sup>2</sup>)
 
−
*[[Cytarabine (Ara-C)]] as follows:
 
−
**Cycles 2 & 4: 2000 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>)
 
−
====Supportive therapy, part B (IVAC)====
 
−
*[[Mesna (Mesnex)]] as follows:
 
−
**Cycles 2 & 4: 1500 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 7500 mg/m<sup>2</sup>)
 
−
====Supportive therapy, all cycles====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 6
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] as follows:
 
−
**Cycles 1 & 3: 50 mg IT once per day on days 1 & 3
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 1 & 3: 12 mg IT once on day 1
 
−
**Cycles 2 & 4: 12 mg IT once on day 5
 
−
*[[Hydrocortisone (Cortef)]] as follows:
 
−
**Cycles 1 & 3: 50 mg IT once on day 1
 
−
'''4 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Lacasce A, Howard O, Lib S, Fisher D, Weng A, Neuberg D, Shipp M. Modified Magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma. 2004 Apr;45(4):761-7. [https://doi.org/10.1080/1042819031000141301 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15160953 PubMed]
+
#Nichols CR, Tricot G, Williams SD, van Besien K, Loehrer PJ, Roth BJ, Akard L, Hoffman R, Goulet R, Wolff SN, Giannone L, Greer J, Einhorn LH, Jansen J. Dose-intensive chemotherapy in refractory germ cell cancer--a phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation. J Clin Oncol. 1989 Jul;7(7):932-9. [https://doi.org/10.1200/jco.1989.7.7.932 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2544687 PubMed]
−
# '''Retrospective:''' Barnes JA, Lacasce AS, Feng Y, Toomey CE, Neuberg D, Michaelson JS, Hochberg EP, Abramson JS. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: a retrospective analysis. Ann Oncol. 2011 Aug;22(8):1859-64. Epub 2011 Feb 21. [https://doi.org/10.1093/annonc/mdq677 link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/21339382 PubMed] content property of [http://hemonc.org HemOnc.org]
+
#'''Retrospective:''' Einhorn LH, Williams SD, Chamness A, Brames MJ, Perkins SM, Abonour R. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med. 2007 Jul 26;357(4):340-8. [https://doi.org/10.1056/NEJMoa067749 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17652649 PubMed]
−
# '''Retrospective:''' Kassam S, Bower M, Lee SM, de Vos J, Fields P, Gandhi S, Nelson M, Montoto S, Tenant-Flowers M, Burns F, Marcus R, Edwards SG, Cwynarski K. A retrospective, multi-center analysis of treatment intensification for HIV-positive patients with high-risk diffuse large B-cell lymphoma. Leuk Lymphoma. 2013 Sep;54(9):1921-7. Epub 2013 Jan 4. [https://doi.org/10.3109/10428194.2012.754024 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23206228 PubMed]
+
=Subsequent lines of therapy=
−
# '''AMC 048:''' Noy A, Lee JY, Cesarman E, Ambinder R, Baiocchi R, Reid E, Ratner L, Wagner-Johnston N, Kaplan L. AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Blood. 2015 Jul 9;126(2):160-6. Epub 2015 May 8. [http://www.bloodjournal.org/content/126/2/160 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497960/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25957391 PubMed] NCT00392834
+
==Etoposide monotherapy {{#subobject:38e630|Regimen=1}}==
−
==R-EPOCH, dose-escalated {{#subobject:3c32e1|Regimen=1}}==
 
−
R-EPOCH: '''<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">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:e2d121|Variant=1}}===
+
===Regimen {{#subobject:d1592b|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 20%"|Study
+
! style="width: 25%" |Study
−
!style="width: 20%"|Years of enrollment
+
! style="width: 25%" |[[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://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858478/ Sparano et al. 2010 (AMC034)]
+
|[https://pubmed.ncbi.nlm.nih.gov/2154858 Miller & Einhorn 1990]
−
|2002-2006
+
| style="background-color:#91cf61" |Phase 2
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ic)
 
−
|[[#EPOCH_88|EPOCH]], then [[#Rituximab_monotherapy_88|R]]
 
−
|style="background-color:#d3d3d3"|Not reported<sup>1</sup>
 
 
|-
 
|-
 
|}
 
|}
−
''<sup>1</sup>While this was a randomized trial, the primary efficacy endpoint was a historical control; see article for details.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once (day not specified), '''given first'''
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[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>)
+
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> PO once per day
−
*[[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>)
+
'''Continued indefinitely'''
−
*[[Cyclophosphamide (Cytoxan)]] by the following laboratory-based criteria:
 
−
**CD4+ count less than 100/uL: 187 mg/m<sup>2</sup> IV over 15 minutes once on day 5
 
−
**CD4+ count greater than 100/uL: 375 mg/m<sup>2</sup> IV over 15 minutes once on day 5
 
−
**In each subsequent cycle, increase dose by 187 mg/m<sup>2</sup> if the neutrophil nadir is greater than 500/uL and platelet nadir is greater than 25 x 10<sup>9</sup>/L. Decrease dose by 187 mg/m<sup>2</sup> if the neutrophil nadir is less than 500/uL or platelet nadir is less than 25 x 10<sup>9</sup>/L.
 
−
*[[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 once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*EITHER [[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting 24 hours after EPOCH is completed and continuing until "neutrophil recovery"—no absolute count specified
 
−
*OR [[Pegfilgrastim (Neulasta)]] 6 mg SC once 24 hours after EPOCH is completed
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO TIW (e.g. Monday, Wednesday, Friday)
 
−
*[[Fluconazole (Diflucan)]] 100 mg PO once per day
 
−
*[[Ciprofloxacin (Cipro)]] 500 mg PO twice per day, starting on day 8 and to continue to at least day 15 or postnadir ANC of at least 1000
 
−
**Other fluoroquinolone can be used at discretion of physician
 
−
'''21-day cycle for 6 to 8 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''AMC034:''' Sparano JA, Lee JY, Kaplan LD, Levine AM, Ramos JC, Ambinder RF, Wachsman W, Aboulafia D, Noy A, Henry DH, Von Roenn J, Dezube BJ, Remick SC, Shah MH, Leichman L, Ratner L, Cesarman E, Chadburn A, Mitsuyasu R; AIDS Malignancy Consortium. Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma. Blood. 2010 Apr 15;115(15):3008-16. Epub 2009 Dec 18. [http://www.bloodjournal.org/content/115/15/3008.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858478/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20023215 PubMed] NCT00049036
+
#Miller JC, Einhorn LH. Phase II study of daily oral etoposide in refractory germ cell tumors. Semin Oncol. 1990 Feb;17(1 Suppl 2):36-9. [https://pubmed.ncbi.nlm.nih.gov/2154858 PubMed]
−
==SC-EPOCH-RR {{#subobject:8d6ea0|Regimen=1}}==
+
==GemOx {{#subobject:fb257|Regimen=1}}==
−
SC-EPOCH-RR: '''<u>S</u>'''hort '''<u>C</u>'''ourse '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, with dose-dense '''<u>R</u>'''ituximab
+
GemOx: '''<u>GEM</u>'''citabine & '''<u>OX</u>'''aliplatin
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:ae5234|Variant=1}}===
+
===Regimen variant #1, 2000/130 {{#subobject:2f29bc|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable" style="width: 60%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 33%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 33%" |Years of enrollment
 +
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858473/ Dunleavy et al. 2010 (NCI 97-C-0040)]
+
|[https://doi.org/10.1093/annonc/mdh103 Pectasides et al. 2004]
−
|style="background-color:#91cf61"|Phase 2
+
|1999-2002
 +
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901044/ Dunleavy et al. 2013 (NCI 93-C-0133)]
+
|[https://doi.org/10.1200/JCO.2004.06.068 Kollmannsberger et al. 2004]
−
|style="background-color:#ffffbe"|Phase 2, <20 pts in this arm
+
|2001-2003
 +
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
−
''NCI 97-C-0040 reports on HIV+ DLBCL patients, whereas NCI 93-C-0133 reports on HIV+ Burkitt lymphoma patients. The regimen is the same.''
+
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 & 5
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[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>)
+
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8, '''given first on day 1'''
−
*[[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>)
+
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given second'''
−
*[[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 once per day on days 1 to 5
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 3 to 5: 12 mg IT once per day on days 1 & 5
 
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Filgrastim (Neupogen)]] 300 mcg SC once per day, starting on day 6, continue until ANC greater than 5k/uL above nadir
+
*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonists]]
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO TIW (e.g. Monday, Wednesday, Friday)  
+
*For patients who developed flu-like symptoms after gemcitabine: [[Dexamethasone (Decadron)]] 2 mg (route not specified) given 3 times on days 1 & 8; 30 minutes prior to [[Gemcitabine (Gemzar)]], 12 hours after [[Gemcitabine (Gemzar)]], and 24 hours after [[Gemcitabine (Gemzar)]]
−
*[[Omeprazole (Prilosec)]] 20 mg PO once per day (or equivalent)
+
'''21-day cycle for up to 6 cycles'''
−
*[[Docusate (Colace)]] and [[Sennosides (Senna)]] 2 tablets PO twice per day as necessary for constipation
+
</div></div><br>
−
*[[Lactulose]] 20 gms PO every 6 hours as necessary for constipation.
+
<div class="toccolours" style="background-color:#eeeeee">
−
'''21-day cycle for 3 to 6 cycles, one cycle beyond CR'''
+
===Regimen variant #2, 2500/130 {{#subobject:2g30bc|Variant=1}}===
−
====Dose modifications====
+
{| class="wikitable" style="width: 40%; text-align:center;"
−
*[[Cyclophosphamide (Cytoxan)]]:
+
! style="width: 25%" |Study
−
**In the subsequent cycle, decrease dose by 187 mg/m<sup>2</sup> if ANC was less than 500/uL for 2 to 4 days or platelets were less than 25 x 10<sup>9</sup>/L for 2 to 4 days.
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
**In the subsequent cycle, decrease dose by 375 mg/m<sup>2</sup> if ANC was less than 500/uL for 5 or more days or platelets were less than 25 x 10<sup>9</sup>/L for 5 or more days.
+
|-
−
**If dose-reduced in prior cycle, increase dose by 187 mg/m<sup>2</sup>, up to maximum of 750 mg/m<sup>2</sup>, if ANC was greater than 500/uL and platelets were greater than 25 x 10<sup>9</sup>/L for the entire cycle.
+
|[https://www.europeanurology.com/article/S0302-2838(06)00578-1 De Giorgi et al. 2006]
 +
| style="background-color:#ffffbe" |Phase 2, <20 pts
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''NCI 97-C-0040:''' Dunleavy K, Little RF, Pittaluga S, Grant N, Wayne AS, Carrasquillo JA, Steinberg SM, Yarchoan R, Jaffe ES, Wilson WH. The role of tumor histogenesis, FDG-PET, and short-course EPOCH with dose-dense rituximab (SC-EPOCH-RR) in HIV-associated diffuse large B-cell lymphoma. Blood. 2010 Apr 15;115(15):3017-24. Epub 2010 Feb 3. [http://www.bloodjournal.org/content/115/15/3017.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858473/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20130244 PubMed] NCT000019253
+
#Kollmannsberger C, Beyer J, Liersch R, Schoeffski P, Metzner B, Hartmann JT, Rick O, Stengele K, Hohloch K, Spott C, Kanz L, Bokemeyer C; German Testicular Cancer Study Group. Combination chemotherapy with gemcitabine plus oxaliplatin in patients with intensively pretreated or refractory germ cell cancer: a study of the German Testicular Cancer Study Group. J Clin Oncol. 2004 Jan 1;22(1):108-14. [https://doi.org/10.1200/JCO.2004.06.068 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14701772 PubMed]
−
# '''NCI 93-C-0133:''' Dunleavy K, Pittaluga S, Shovlin M, Steinberg SM, Cole D, Grant C, Widemann B, Staudt LM, Jaffe ES, Little RF, Wilson WH. Low-intensity therapy in adults with Burkitt's lymphoma. N Engl J Med. 2013 Nov 14;369(20):1915-25. [https://doi.org/10.1056/NEJMoa1308392 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24224624 PubMed] NCT00001337
+
#Pectasides D, Pectasides M, Farmakis D, Aravantinos G, Nikolaou M, Koumpou M, Gaglia A, Kostopoulou V, Mylonakis N, Skarlos D. Gemcitabine and oxaliplatin (GEMOX) in patients with cisplatin-refractory germ cell tumors: a phase II study. Ann Oncol. 2004 Mar;15(3):493-7. [https://doi.org/10.1093/annonc/mdh103 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14998855 PubMed]
−
==Stanford V {{#subobject:c00372|Regimen=1}}==
+
#De Giorgi U, Rosti G, Aieta M, Testore F, Burattini L, Fornarini G, Naglieri E, Lo Re G, Zumaglini F, Marangolo M. Phase II study of oxaliplatin and gemcitabine salvage chemotherapy in patients with cisplatin-refractory nonseminomatous germ cell tumor. Eur Urol. 2006 Nov;50(5):1032-8. Epub 2006 May 23. [https://www.europeanurology.com/article/S0302-2838(06)00578-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16757095 PubMed]
 +
==Gemcitabine, Oxaliplatin, Paclitaxel {{#subobject:6f8727|Regimen=1}}==
 +
GOP: '''<u>G</u>'''emcitabine, '''<u>O</u>'''xaliplatin, '''<u>P</u>'''aclitaxel
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:19ebaa|Variant=1}}===
+
===Regimen {{#subobject:8a2aaa|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable" style="width: 60%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 33%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 33%" |Years of enrollment
 +
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/100/6/1984.long Spina et al. 2002]
+
|[https://doi.org/10.1093/annonc/mdm526 Bokemeyer et al. 2007]
−
|style="background-color:#91cf61"|Phase 2
+
|2003-2006
 +
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
−
''Note: this regimen was for HIV-associated Hodgkin lymphoma, unfavorable stage I or advanced stage.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per week on weeks 1, 3, 5, 7, 9, 11
+
*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
−
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV once per week on weeks 1, 3, 5, 7, 9, 11
+
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over greater than 2 hours once on day 1
−
*[[Mechlorethamine (Mustargen)]] 6 mg/m<sup>2</sup> IV once per week on weeks 1, 5, 9
+
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 8
−
*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV once per day for two successive days on weeks 3, 7, 11
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per week on weeks 2, 4, 6, 8, 10, 12
 
−
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV once per week on weeks 2, 4, 6, 8, 10, 12
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] as follows:
 
−
**Weeks 1 to 10: 40 mg/m<sup>2</sup> PO every other day
 
−
**Weeks 11 & 12: taper by 10 mg/m<sup>2</sup> every other day until off
 
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 3 to 7, 9 to 13, 17 to 21, 23 to 26
+
*"[[:Category:Emesis prevention|Antiemetic prophylaxis]] was left to the decision of the treating physician, but a combination of a [[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] and [[Dexamethasone (Decadron)|dexamethasone]] was proposed."
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO once per day throughout the course of treatment
+
*[[Dexamethasone (Decadron)]] 20 mg IV once per day on days 1 & 8; 30 minutes prior to [[Paclitaxel (Taxol)]]
−
*[[Fluconazole (Diflucan)]] 100 mg PO once per day throughout the course of treatment
+
*[[Diphenhydramine (Benadryl)]] 50 mg IV once per day on days 1 & 8; 20 minutes prior to [[Paclitaxel (Taxol)]]
−
'''12-week course'''
+
*[[Cimetidine (Tagamet)]] 300 mg IV once per day on days 1 & 8; 20 minutes prior to [[Paclitaxel (Taxol)]]
−
</div>
+
'''21-day cycles, given for 2 cycles beyond the best response, up to a maximum of 8 cycles'''
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*PR: [[#Radiation_therapy|IFRT]] x 36 Gy
 
−
*CR with initial bulky disease (5 cm or larger): [[#Radiation_therapy|IFRT]] x 36 Gy
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Spina M, Gabarre J, Rossi G, Fasan M, Schiantarelli C, Nigra E, Mena M, Antinori A, Ammassari A, Talamini R, Vaccher E, di Gennaro G, Tirelli U. Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection. Blood. 2002 Sep 15;100(6):1984-8. [http://www.bloodjournal.org/content/100/6/1984.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12200356 PubMed]
+
#Bokemeyer C, Oechsle K, Honecker F, Mayer F, Hartmann JT, Waller CF, Böhlke I, Kollmannsberger C; German Testicular Cancer Study Group. Combination chemotherapy with gemcitabine, oxaliplatin, and paclitaxel in patients with cisplatin-refractory or multiply relapsed germ-cell tumors: a study of the German Testicular Cancer Study Group. Ann Oncol. 2008 Mar;19(3):448-53. Epub 2007 Nov 15. [https://doi.org/10.1093/annonc/mdm526 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18006893 PubMed]
−
=Consolidation and/or maintenance after upfront therapy=
+
==Gemcitabine & Paclitaxel {{#subobject:7a296e|Regimen=1}}==
−
==Radiation therapy {{#subobject:3e41de|Regimen=1}}==
 
−
IFRT: '''<u>I</u>'''nvolved '''<u>F</u>'''ield '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, 36 Gy of IFRT {{#subobject:7f22e5|Variant=1}}===
+
===Regimen variant #1 {{#subobject:2befdd|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 25%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/100/6/1984.long Spina et al. 2002]
+
|[https://doi.org/10.1200/jco.2002.07.158 Hinton et al. 2002 (ECOG E9897)]
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Stanford_V|Stanford V]] x 12 wk
 
−
</div>
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Radiotherapy====
+
====Chemotherapy====
−
*[[External beam radiotherapy]] 36 Gy in 2 Gy fractions, 5 days per week
+
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15, '''given second'''
−
'''4-week course'''
+
*[[Paclitaxel (Taxol)]] 110 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, '''given first'''
 +
====Supportive therapy====
 +
*[[Dexamethasone (Decadron)]] 20 mg IV or PO once per day on days 1, 8, 15; 60 minutes prior to each dose of [[Paclitaxel (Taxol)]]
 +
*[[Diphenhydramine (Benadryl)]] 50 mg IV once per day on days 1, 8, 15; 60 minutes prior to each dose of [[Paclitaxel (Taxol)]]
 +
*One of the following H2-blockers:
 +
**[[Cimetidine (Tagamet)]] 300 mg IV once per day on days 1, 8, 15; 60 minutes prior to each dose of [[Paclitaxel (Taxol)]]
 +
**[[Ranitidine (Zantac)]] 50 mg IV once per day on days 1, 8, 15; 60 minutes prior to each dose of [[Paclitaxel (Taxol)]]
 +
'''28-day cycle for up to 6 cycles'''
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, 40 Gy of IFRT {{#subobject:029c6c|Variant=1}}===
+
===Regimen variant #2 {{#subobject:5db67f|Variant=1}}===
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 33%"|Study
+
! style="width: 25%" |Study
−
!style="width: 33%"|Years of enrollment
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ Kaplan et al. 2005 (AMC010)]
+
|[https://doi.org/10.1200/jco.2006.07.7271 Einhorn et al. 2007b]
−
|1998-2002
+
| style="background-color:#91cf61" |Phase 2
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
 
|-
 
|-
 
|}
 
|}
−
''Intended for patients with stage I, IE, or nonbulky stage II disease.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-CHOP|R-CHOP]] x 3
 
−
</div>
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Radiotherapy====
+
====Chemotherapy====
−
*[[External beam radiotherapy]] to a total dose of at least 40 Gy
+
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15, '''given second'''
−
'''One course'''
+
*[[Paclitaxel (Taxol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, '''given first'''
−
</div>
+
====Supportive therapy====
−
<div class="toccolours" style="background-color:#cbd5e7">
+
*[[Dexamethasone (Decadron)]] 20 mg IV or PO once per day on days 1, 8, 15; 30 minutes prior to [[Paclitaxel (Taxol)]]
−
====Subsequent treatment====
+
*[[Diphenhydramine (Benadryl)]] 50 mg IV once per day on days 1, 8, 15; 30 minutes prior to [[Paclitaxel (Taxol)]]
−
*PR/CR: [[#Rituximab_monotherapy|Rituximab]] maintenance
+
*One of the following H2-blockers:
 +
**[[Cimetidine (Tagamet)]] 300 mg IV once per day on days 1, 8, 15; 30 minutes prior to [[Paclitaxel (Taxol)]]
 +
**[[Ranitidine (Zantac)]] 50 mg IV once per day on days 1, 8, 15; 30 minutes prior to [[Paclitaxel (Taxol)]]
 +
*Growth factors "used only for prolonged granulocytopenia."
 +
'''28-day cycle for up to 6 cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Spina M, Gabarre J, Rossi G, Fasan M, Schiantarelli C, Nigra E, Mena M, Antinori A, Ammassari A, Talamini R, Vaccher E, di Gennaro G, Tirelli U. Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection. Blood. 2002 Sep 15;100(6):1984-8. [http://www.bloodjournal.org/content/100/6/1984.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12200356 PubMed]
+
#'''ECOG E9897:''' Hinton S, Catalano P, Einhorn LH, Loehrer PJ Sr, Kuzel T, Vaughn D, Wilding G. Phase II study of paclitaxel plus gemcitabine in refractory germ cell tumors (E9897): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2002 Apr 1;20(7):1859-63. [https://doi.org/10.1200/jco.2002.07.158 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11919245 PubMed]
−
# '''AMC010:''' Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. [http://www.bloodjournal.org/content/106/5/1538.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15914552 PubMed] NCT00003595
+
#Einhorn LH, Brames MJ, Juliar B, Williams SD. Phase II study of paclitaxel plus gemcitabine salvage chemotherapy for germ cell tumors after progression following high-dose chemotherapy with tandem transplant. J Clin Oncol. 2007 Feb 10;25(5):513-6. [https://doi.org/10.1200/jco.2006.07.7271 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17290059 PubMed]
−
==Rituximab monotherapy {{#subobject:d2786f|Regimen=1}}==
+
==Oxaliplatin & Bevacizumab {{#subobject:1b3daf|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:e49f13|Variant=1}}===
+
===Regimen {{#subobject:704dc6|Variant=1}}===
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 33%"|Study
+
! style="width: 25%" |Study
−
!style="width: 33%"|Years of enrollment
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ Kaplan et al. 2005 (AMC010)]
+
|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2014&issue=10000&article=00006&type=abstract Jain et al. 2014]
−
|1998-2002
+
| style="background-color:#91cf61" |Phase 2
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*AMC010, early disease: [[#Radiation_therapy|IFRT]]
 
−
*AMC010, advanced disease: [[#R-CHOP|R-CHOP]]
 
−
</div>
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
 
====Targeted therapy====
 
====Targeted therapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1
−
'''1-month cycle for 3 cycles'''
+
'''14-day cycle for a maximum of 14 cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. [http://www.bloodjournal.org/content/106/5/1538.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895225/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15914552 PubMed] NCT00003595
+
<!-- # '''Abstract:''' A. Jain, M. J. Brames, D. J. Vaughn, L. H. Einhorn. Phase II clinical trial of oxaliplatin and bevacizumab in refractory metastatic germ cell tumors (GCT). J Clin Oncol 29: 2011 (suppl; abstr 4579). [http://meetinglibrary.asco.org/content/75952-102 link to abstract] '''contains dosing details in manuscript''' -->
−
=Consolidation after salvage therapy=
+
#Jain A, Brames MJ, Vaughn DJ, Einhorn LH. Phase II clinical trial of oxaliplatin and bevacizumab in refractory germ cell tumors. Am J Clin Oncol. 2014 Oct;37(5):450-3. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2014&issue=10000&article=00006&type=abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/23388561 PubMed]
−
==BEAM, then auto HSCT {{#subobject:f357b4|Regimen=1}}==
+
==Sunitinib monotherapy {{#subobject:a97a47|Regimen=1}}==
−
BEAM: '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:9a79af|Variant=1}}===
+
===Regimen variant #1 {{#subobject:52af77|Variant=1}}===
 
{| class="wikitable" style="width: 60%; text-align:center;"  
 
{| class="wikitable" style="width: 60%; text-align:center;"  
−
!style="width: 33%"|Study
+
! style="width: 33%" |Study
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 33%" |Years of enrollment
−
!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1007/s10637-009-9280-2 Feldman et al. 2010]
 +
|NR
 +
| style="background-color:#ffffbe" |Phase 2, <20 pts
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2003.06.039 Re et al. 2003]
+
|}
−
|style="background-color:#91cf61"|Phase 2
+
<div class="toccolours" style="background-color:#b3e2cd">
−
|
+
====Targeted therapy====
 +
*[[Sunitinib (Sutent)]] 37.5 mg PO once per day
 +
'''42-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2 {{#subobject:80e2c3|Variant=1}}===
 +
{| class="wikitable" style="width: 60%; text-align:center;"
 +
! style="width: 33%" |Study
 +
! style="width: 33%" |Years of enrollment
 +
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000843/ Alvarnas et al. 2016 (BMT CTN 0803/AMC 071)]
+
|[https://doi.org/10.1093/annonc/mdr026 Oechsle et al. 2011]
−
|style="background-color:#91cf61"|Phase 2
+
|2007-2010
−
|1-year OS: 87% (95% CI, 72-94.5)
+
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
−
''Note: days of chemotherapy are slightly different in Re et al. 2003; see paper for details.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy====
+
====Targeted therapy====
−
*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -6
+
*[[Sunitinib (Sutent)]] 50 mg PO once per day on days 1 to 28
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV every 12 hours on days -5 to -2 (total dose: 800 mg/m<sup>2</sup>)
+
'''42-day cycles'''
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days -5 to -2 (total dose: 800 mg/m<sup>2</sup>)
 
−
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -1
 
−
'''Hematopoietic stem cells are reinfused on day 0'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Re A, Cattaneo C, Michieli M, Casari S, Spina M, Rupolo M, Allione B, Nosari A, Schiantarelli C, Vigano M, Izzi I, Ferremi P, Lanfranchi A, Mazzuccato M, Carosi G, Tirelli U, Rossi G. High-dose therapy and autologous peripheral-blood stem-cell transplantation as salvage treatment for HIV-associated lymphoma in patients receiving highly active antiretroviral therapy. J Clin Oncol. 2003 Dec 1;21(23):4423-7. Epub 2003 Oct 27. [https://doi.org/10.1200/jco.2003.06.039 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14581441 PubMed]
+
#Feldman DR, Turkula S, Ginsberg MS, Ishill N, Patil S, Carousso M, Bosl GJ, Motzer RJ. Phase II trial of sunitinib in patients with relapsed or refractory germ cell tumors. Invest New Drugs. 2010 Aug;28(4):523-8. [https://doi.org/10.1007/s10637-009-9280-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19547919 PubMed]
−
# '''BMT CTN 0803/AMC 071:''' Alvarnas JC, Le Rademacher J, Wang Y, Little RF, Akpek G, Ayala E, Devine S, Baiocchi R, Lozanski G, Kaplan L, Noy A, Popat U, Hsu J, Morris LE Jr, Thompson J, Horowitz MM, Mendizabal A, Levine A, Krishnan A, Forman SJ, Navarro WH, Ambinder R. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial. Blood. 2016 Aug 25;128(8):1050-8. Epub 2016 Jun 13. [http://www.bloodjournal.org/content/128/8/1050.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000843/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27297790 PubMed] NCT01141712
+
<!-- # '''Abstract:''' C. K. Kollmannsberger, K. Oechsle, T. Cheng, F. Mayer, P. Czaykowski, E. Winquist, L. Wood, M. Fenner, K. N. Chi and C. Bokemeyer. Sunitinib in patients with multiply relapsed or cisplatin-refractory germ cell cancer: A CUOG/GTCSG cooperative phase II study. Journal of Clinical Oncology, 2010 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 28, No 15_suppl (May 20 Supplement), 2010: 4582. -->
−
[[Category:HIV-associated lymphoma regimens]]
+
#Oechsle K, Honecker F, Cheng T, Mayer F, Czaykowski P, Winquist E, Wood L, Fenner M, Glaesener S, Hartmann JT, Chi K, Bokemeyer C, Kollmannsberger C; Canadian Urologic Oncology Group; German Testicular Cancer Study Group. Preclinical and clinical activity of sunitinib in patients with cisplatin-refractory or multiply relapsed germ cell tumors: a Canadian Urologic Oncology Group/German Testicular Cancer Study Group cooperative study. Ann Oncol. 2011 Dec;22(12):2654-60. Epub 2011 Mar 17. [https://doi.org/10.1093/annonc/mdr026 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21415240 PubMed]
 +
= Statistics =
 +
* Stage I seminoma surveillance relapse - Warde P, Specht L, Horwich A, Oliver T, Panzarella T, Gospodarowicz M, von der Maase H. Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis. J Clin Oncol. 2002 Nov 15;20(22):4448-52. [https://dx.doi.org/10.1200/JCO.2002.01.038 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12431967/ PubMed]
 +
=Patient information=
 +
*[https://thetcrc.org/ Testicular Cancer Resource Center] - detailed website with information for patients and families about testicular cancer
 +
[[Category:Testicular cancer regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
−
[[Category:Aggressive lymphomas]]
+
[[Category:Genitourinary cancers]]

Revision as of 11:41, 16 October 2022

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Section editor transclusions Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the historical regimens page. If you still can't find it, please let us know so we can add it!
Note: Except for primary treatment for stage I seminoma, these regimens are generally applicable to seminoma and non-seminoma histologies.

0 regimens on this page
0 variants on this page


Guidelines

ESMO

Older

ESMO-EURACAN

NCCN

Adjuvant therapy for resectable disease

BEP

BEP: Bleomycin, Etoposide, Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Albers et al. 2008 (AUO AH 01/94) 1996-2005 Phase 3 (E-switch-ooc) RPLND Superior RFS

Preceding treatment

Chemotherapy

15-day course

References

  1. AUO AH 01/94: Albers P, Siener R, Krege S, Schmelz HU, Dieckmann KP, Heidenreich A, Kwasny P, Pechoel M, Lehmann J, Kliesch S, Köhrmann KU, Fimmers R, Weissbach L, Loy V, Wittekind C, Hartmann M; German Testicular Cancer Study Group. Randomized phase III trial comparing retroperitoneal lymph node dissection with one course of bleomycin and etoposide plus cisplatin chemotherapy in the adjuvant treatment of clinical stage I Nonseminomatous testicular germ cell tumors: AUO trial AH 01/94 by the German Testicular Cancer Study Group. J Clin Oncol. 2008 Jun 20;26(18):2966-72. Epub 2008 May 5. Erratum in: J Clin Oncol. 2010 Mar 10;28(8):1439. Dosage error in article text. link to original article contains dosing details in manuscript PubMed
    1. Update: Hiester A, Fingerhut A, Niegisch G, Siener R, Krege S, Schmelz HU, Dieckmann KP, Heidenreich A, Kwasny P, Pechoel M, Lehmann J, Kliesch S, Köhrmann KU, Fimmers R, Loy V, Wittekind C, Hartmann M, Albers P. Late toxicities and recurrences in patients with clinical stage I non-seminomatous germ cell tumours after 1 cycle of adjuvant bleomycin, etoposide and cisplatin versus primary retroperitoneal lymph node dissection - A 13-year follow-up analysis of a phase III trial cohort. Eur J Cancer. 2021 Sep;155:64-72. Epub 2021 Aug 6. link to original article PubMed

Carboplatin monotherapy

Regimen variant #1

Study Years of enrollment Evidence Comparator Comparative Efficacy
Oliver et al. 2005 (MRC TE19/EORTC 30982) 1996-2001 Phase 3 (E-switch-ooc) Radiation therapy Seems to have non-inferior RFS

Preceding treatment

Chemotherapy

  • Carboplatin (Paraplatin) AUC 7 IV once on day 1
    • AUC 7 was described in Oliver et al. 2005 & Oliver et al. 2011 as [7 x (GFR + 25)] mg. eGFR was calculated by EDTA; if CrCl via 24-hour urine collection was used, 90% of the [7 x (GFR + 25)] mg dose was used. The Calvert formula for carboplatin dosing is: Dose (mg) = (target AUC) x (GFR + 25).

One dose


Regimen variant #2, 2 doses carboplatin

Study Evidence
Aparicio et al. 2005 (Second Spanish Germ Cell Cancer Group study) Non-randomized
Aparicio et al. 2011 (Third Spanish Germ Cell Cancer Group study) Non-randomized

Patients with stage I seminoma and local risk factors:

  1. Tumor greater than 4 cm
  2. Rete testis invasion

Patients in Aparicio et al. 2005 had at least one risk factor; patients in Aparicio et al. 2011 had at both risk factors.

Preceding treatment

Chemotherapy

Supportive therapy

21-day cycle for 2 cycles

References

  1. MRC TE19/EORTC 30982: Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, de Wit R, Aass N, Graham JD, Coleman R, Kirk SJ, Stenning SP; MRC; EORTC. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet. 2005 Jul 23-29;366(9482):293-300. link to original article contains dosing details in manuscript PubMed NCT00003014
    1. Update: Oliver RT, Mead GM, Rustin GJ, Joffe JK, Aass N, Coleman R, Gabe R, Pollock P, Stenning SP. Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214). J Clin Oncol. 2011 Mar 10;29(8):957-62. Epub 2011 Jan 31. link to original article contains dosing details in manuscript PubMed
  2. Second Spanish Germ Cell Cancer Group study: Aparicio J, Germà JR, García del Muro X, Maroto P, Arranz JA, Sáenz A, Barnadas A, Dorca J, Gumà J, Olmos D, Bastús R, Carles J, Almenar D, Sánchez M, Paz-Ares L, Satrústegui JJ, Mellado B, Balil A, López-Brea M, Sánchez A; Spanish Germ Cell Cancer Cooperative Group. Risk-adapted management for patients with clinical stage I seminoma: the Second Spanish Germ Cell Cancer Cooperative Group study. J Clin Oncol. 2005 Dec 1;23(34):8717-23. Epub 2005 Oct 31. link to original article contains dosing details in manuscript PubMed
  3. Third Spanish Germ Cell Cancer Group study: Aparicio J, Maroto P, del Muro XG, Gumà J, Sánchez-Muñoz A, Margelí M, Doménech M, Bastús R, Fernández A, López-Brea M, Terrassa J, Meana A, del Prado PM, Sastre J, Satrústegui JJ, Gironés R, Robert L, Germà JR; Spanish Germ Cell Cancer Cooperative Group. Risk-adapted treatment in clinical stage I testicular seminoma: the third Spanish Germ Cell Cancer Group study. J Clin Oncol. 2011 Dec 10;29(35):4677-81. Epub 2011 Oct 31. link to original article contains dosing details in manuscript PubMed

Radiation therapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Jones et al. 2005 (MRC TE18/EORTC 30942) 1995-1998 Phase 3 (C) RT; lower-dose Did not meet primary endpoint of RFS24
Oliver et al. 2005 (MRC TE19/EORTC 30982) 1996-2001 Phase 3 (C) Carboplatin Seems to have non-inferior RFS

Note: radiation details are available in the references.

Preceding treatment

Radiotherapy

References

  1. MRC TE18/EORTC 30942: Jones WG, Fossa SD, Mead GM, Roberts JT, Sokal M, Horwich A, Stenning SP; MRC; EORTC. Randomized trial of 30 versus 20 Gy in the adjuvant treatment of stage I testicular seminoma: a report on Medical Research Council Trial TE18, European Organisation for the Research and Treatment of Cancer Trial 30942 (ISRCTN18525328). J Clin Oncol. 2005 Feb 20;23(6):1200-8. link to original article PubMed
  2. MRC TE19/EORTC 30982: Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, de Wit R, Aass N, Graham JD, Coleman R, Kirk SJ, Stenning SP; MRC; EORTC. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet. 2005 Jul 23-29;366(9482):293-300. link to original article contains dosing details in manuscript PubMed NCT00003014
    1. Update: Oliver RT, Mead GM, Rustin GJ, Joffe JK, Aass N, Coleman R, Gabe R, Pollock P, Stenning SP. Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214). J Clin Oncol. 2011 Mar 10;29(8):957-62. Epub 2011 Jan 31. link to original article contains dosing details in manuscript PubMed

Upfront therapy for disseminated disease

BEP

BEP: Bleomycin, Etoposide, Platinol (Cisplatin)
PVP16B: Platinol (Cisplatin), VP-16 (Etoposide), Bleomycin

Regimen variant #1, 90/500/100 x 3 ("standard" BEP)

Study Years of enrollment Evidence Comparator Comparative Efficacy
Einhorn et al. 1989 1984-1987 Phase 3 (E-de-esc) BEP x 4 Seems to have equivalent DFS
Toner et al. 2001 1994-2000 Phase 3 (C) Modified BEP; 30/360/100 Seems to have superior OS1
de Wit et al. 2001 1995-1998 Phase 3 (E-de-esc) 1. BEP x 4 Equivalent PFS
2. BEP; 3-day etoposide x 3
3. BEP; 3-day etoposide x 4 		Equivalent PFS

1Reported efficacy for Toner et al. 2001 is based on the 2010 update.

Chemotherapy

21-day cycle for 3 cycles


Regimen variant #2, 90/500/100 x 4 ("standard" BEP)

Study Years of enrollment Evidence Comparator Comparative Efficacy
Williams et al. 1987a 1982-1984 Phase 3 (E-switch-ic) BVP Did not meet primary endpoint of OS1
Einhorn et al. 1989 1984-1987 Phase 3 (C) BEP x 3 Seems to have equivalent DFS
Nichols et al. 1998 (ECOG E3887) 1987-1992 Phase 3 (C) VIP Did not meet efficacy endpoints
de Wit et al. 2001 1995-1998 Phase 3 (C) 1. BEP x 3 Equivalent PFS
2. BEP; 3-day etoposide x 3
3. BEP; 3-day etoposide x 4 		Equivalent PFS
Culine et al. 2008 (T93MP) 1994-2000 Phase 3 (C) CISCA/VB Did not meet primary endpoint of FRR
Motzer et al. 2007 (SWOG-9442) 1994-2003 Phase 3 (C) BEP x 2, then HDCT x 2 Did not meet primary endpoint of durable CR at 12 mo
de Wit et al. 2012 (EORTC 30983) 1998-2009 Phase 3 (C) T-BEP Seems to have inferior PFS36
Daugaard et al. 2010 (EORTC 30974) 1999-2007 Phase 3 (C) BEP x 1, then HDCT x 3 Might have inferior FFS
Fizazi et al. 2014 (GETUG 13) 2003-2012 Risk-adapted therapy

1There seemed to be a survival advantage in the high tumor volume subgroup, but no difference was seen in the overall group.
Note: this was the favorable decline rate subset of GETUG 13.

Chemotherapy

  • Bleomycin (Blenoxane) 30 units IV bolus once per day on days 1, 8, 15
    • Note: Williams et al. 1987 gave bleomycin on days 2, 9, 16
    • Note: de Wit et al. 2001 only used bleomycin for cycles 1 to 3
  • Etoposide (Vepesid) 100 mg/m2 in 500 mL normal saline IV over 30 to 60 minutes once per day on days 1 to 5
  • Cisplatin (Platinol) 20 mg/m2 IV over 15 to 60 minutes once per day on days 1 to 5

Supportive therapy

  • (as described in Nichols et al. 1998):
  • Normal saline 100 mL/hour IV over 12 hours once per day on days 1 to 5, prior to Cisplatin (Platinol)
  • Normal saline 100 mL/hour IV throughout the 5 day course of Cisplatin (Platinol), ending 6 hours after each cycle's last cisplatin dose
  • G-CSF (type not specified) 5 mcg/kg SC once per day on days 7, 9 to 14, 16, 17

21-day cycle for 4 cycles


Regimen variant #3, 90/495/100 x 3 (3-day etoposide)

Study Years of enrollment Evidence Comparator Comparative Efficacy
de Wit et al. 2001 1995-1998 Phase 3 (E-de-esc) 1. BEP x 3
2. BEP x 4 		Equivalent PFS
3. BEP; 3-day etoposide x 4 Equivalent PFS

Chemotherapy

21-day cycle for 3 cycles


Regimen variant #4, 90/495/100 x 4 (3-day etoposide)

Study Years of enrollment Evidence Comparator Comparative Efficacy
de Wit et al. 2001 1995-1998 Phase 3 (E-esc) 1. BEP x 3
2. BEP x 4 		Equivalent PFS
3. BEP; 3-day etoposide x 3 Equivalent PFS

Chemotherapy

21-day cycle for 4 cycles


Regimen variant #5, 45/500/100 (modified BEP)

Study Evidence
Fosså et al. 2005 (EORTC 30948) Phase 2

Note that the dose of bleomycin is lower than standard BEP.

Preceding treatment

Chemotherapy

21-day cycle for 3 cycles

References

  1. Williams SD, Birch R, Einhorn LH, Irwin L, Greco FA, Loehrer PJ. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med. 1987 Jun 4;316(23):1435-40. link to original article contains dosing details in manuscript PubMed
  2. Einhorn LH, Williams SD, Loehrer PJ, Birch R, Drasga R, Omura G, Greco FA; Southeastern Cancer Study Group. Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol. J Clin Oncol. 1989 Mar;7(3):387-91. link to original article PubMed
    1. Update: Saxman SB, Finch D, Gonin R, Einhorn LH. Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide, and cisplatin in favorable-prognosis germ-cell tumors: the Indiana University experience. J Clin Oncol. 1998 Feb;16(2):702-6. link to original article contains dosing details in manuscript PubMed
  3. ECOG E3887: Nichols CR, Catalano PJ, Crawford ED, Vogelzang NJ, Einhorn LH, Loehrer PJ. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol. 1998 Apr;16(4):1287-93. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
    1. Update: Hinton S, Catalano PJ, Einhorn LH, Nichols CR, Crawford ED, Vogelzang N, Trump D, Loehrer PJ Sr. Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors: final analysis of an intergroup trial. Cancer. 2003 Apr 15;97(8):1869-75. link to original article PubMed
  4. Toner GC, Stockler MR, Boyer MJ, Jones M, Thomson DB, Harvey VJ, Olver IN, Dhillon H, McMullen A, Gebski VJ, Levi JA, Simes RJ; Australian and New Zealand Germ Cell Trial Group. Comparison of two standard chemotherapy regimens for good-prognosis germ-cell tumours: a randomised trial. Lancet. 2001 Mar 10;357(9258):739-45. link to original article contains dosing details in abstract PubMed
    1. Update: Grimison PS, Stockler MR, Thomson DB, Olver IN, Harvey VJ, Gebski VJ, Lewis CR, Levi JA, Boyer MJ, Gurney H, Craft P, Boland AL, Simes RJ, Toner GC. Comparison of two standard chemotherapy regimens for good-prognosis germ cell tumors: updated analysis of a randomized trial. J Natl Cancer Inst. 2010 Aug 18;102(16):1253-62. Epub 2010 Jul 14. link to original article PubMed
  5. de Wit R, Roberts JT, Wilkinson PM, de Mulder PH, Mead GM, Fosså SD, Cook P, de Prijck L, Stenning S, Collette L; European Organisation for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group; MRC. Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized study of the European Organisation for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council. J Clin Oncol. 2001 Mar 15;19(6):1629-40. link to original article contains dosing details in manuscript PubMed
  6. EORTC 30948: Fosså SD, Paluchowska B, Horwich A, Kaiser G, de Mulder PH, Koriakine O, van Oosterom AT, de Prijck L, Collette L, de Wit R; EORTC GU Group. Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948). Br J Cancer. 2005 Nov 28;93(11):1209-14. link to original article contains dosing details in manuscript link to PMC article PubMed
  7. SWOG-9442: Motzer RJ, Nichols CJ, Margolin KA, Bacik J, Richardson PG, Vogelzang NJ, Bajorin DF, Lara PN Jr, Einhorn L, Mazumdar M, Bosl GJ. Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors. J Clin Oncol. 2007 Jan 20;25(3):247-56. link to original article refers to Williams et al. 1998 PubMed NCT00002596
  8. T93MP: Culine S, Kramar A, Théodore C, Geoffrois L, Chevreau C, Biron P, Nguyen BB, Héron JF, Kerbrat P, Caty A, Delva R, Fargeot P, Fizazi K, Bouzy J, Droz JP; Genito-Urinary Group of the French Federation of Cancer Centers. Randomized trial comparing bleomycin/etoposide/cisplatin with alternating cisplatin/cyclophosphamide/doxorubicin and vinblastine/bleomycin regimens of chemotherapy for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP. J Clin Oncol. 2008 Jan 20;26(3):421-7. link to original article contains dosing details in manuscript PubMed
  9. EORTC 30974: Daugaard G, Skoneczna I, Aass N, De Wit R, De Santis M, Dumez H, Marreaud S, Collette L, Lluch JR, Bokemeyer C, Schmoll HJ. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer: an intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974). Ann Oncol. 2011 May;22(5):1054-61. Epub 2010 Nov 8. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00003941
  10. EORTC 30983: de Wit R, Skoneczna I, Daugaard G, De Santis M, Garin A, Aass N, Witjes AJ, Albers P, White JD, Germa-Lluch JR, Marreaud S, Collette L. Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer: intergroup study EORTC 30983. J Clin Oncol. 2012 Mar 10;30(8):792-9. Epub 2012 Jan 23. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00003643
  11. GETUG 13: Fizazi K, Pagliaro L, Laplanche A, Fléchon A, Mardiak J, Geoffrois L, Kerbrat P, Chevreau C, Delva R, Rolland F, Theodore C, Roubaud G, Gravis G, Eymard JC, Malhaire JP, Linassier C, Habibian M, Martin AL, Journeau F, Reckova M, Logothetis C, Culine S. Personalised chemotherapy based on tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial. Lancet Oncol. 2014 Dec;15(13):1442-50. Epub 2014 Nov 13. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00104676

Accelerated BEP

Accelerated BEP: Accelerated Bleomycin, Etoposide, Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence
Grimison et al. 2014 2008-2010 Phase 2

Chemotherapy

Supportive therapy

14-day cycle for 4 cycles

References

  1. Grimison PS, Stockler MR, Chatfield M, Thomson DB, Gebski V, Friedlander M, Boland AL, Houghton B, Gurney H, Rosenthal M, Singhal N, Kichenadasse G, Wong SS, Lewis CR, Vasey PA, Toner GC; Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Accelerated BEP for metastatic germ cell tumours: a multicenter phase II trial by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). Ann Oncol. 2014 Jan;25(1):143-8. link to original article contains dosing details in abstract PubMed ACTRN 12607000294459

Bleomycin & Vincristine (BO)

BO: Bleomycin & Oncovin (Vincristine)

Regimen

Study Evidence
Fosså et al. 2005 (EORTC 30948) Phase 2

Preceding treatment

Chemotherapy

14-day cycle for 1 cycle

Subsequent treatment

BEP; modified x 3

References

  1. EORTC 30948: Fosså SD, Paluchowska B, Horwich A, Kaiser G, de Mulder PH, Koriakine O, van Oosterom AT, de Prijck L, Collette L, de Wit R; EORTC GU Group. Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948). Br J Cancer. 2005 Nov 28;93(11):1209-14. link to original article contains dosing details in manuscript link to PMC article PubMed

C-BOP

C-BOP: Cisplatin, Bleomycin, Oncovin (Vincristine), Paraplatin (Carboplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Fosså et al. 2005 (EORTC 30948) 1996-1998 Phase 2
Huddart et al. 2014 (MRC TE23) 2005-2009 Randomized Phase 2 (E-esc) BEP Seems to have superior FRR

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

14-day cycle for 2 cycles

Subsequent treatment

  • BO x 1, then BEP; modified x 3

References

  1. EORTC 30948: Fosså SD, Paluchowska B, Horwich A, Kaiser G, de Mulder PH, Koriakine O, van Oosterom AT, de Prijck L, Collette L, de Wit R; EORTC GU Group. Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948). Br J Cancer. 2005 Nov 28;93(11):1209-14. link to original article contains dosing details in manuscript link to PMC article PubMed
  2. MRC TE23: Huddart RA, Gabe R, Cafferty FH, Pollock P, White JD, Shamash J, Cullen MH, Stenning SP; TE23 Trial Management Group and Collaborators; National Cancer Research Institute Testis Cancer Clinical Studies Group. A randomised phase 2 trial of intensive induction chemotherapy (CBOP/BEP) and standard BEP in poor-prognosis germ cell tumours (MRC TE23, CRUK 05/014, ISRCTN 53643604). Eur Urol. 2015 Mar;67(3):534-43. Epub 2014 Jul 4. link to original article link to PMC article PubMed ISRCTN53643604

Cisplatin & Etoposide (EP)

EP: Etoposide, Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Bosl et al. 1988 1982-1986 Phase 3 (E-de-esc) VAB-6 Did not meet efficacy endpoints
Bajorin et al. 1993 1986-1990 Phase 3 (C) CE Seems to have superior EFS

Chemotherapy

21-day cycle for 4 cycles

References

  1. Bosl GJ, Geller NL, Bajorin D, Leitner SP, Yagoda A, Golbey RB, Scher H, Vogelzang NJ, Auman J, Carey R, Fair WR, Herr H, Morse M, Sogani P, Whitmore W. A randomized trial of etoposide + cisplatin versus vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin in patients with good-prognosis germ cell tumors. J Clin Oncol. 1988 Aug;6(8):1231-8. link to original article PubMed
    1. Update: Xiao H, Mazumdar M, Bajorin DF, Sarosdy M, Vlamis V, Spicer J, Ferrara J, Bosl GJ, Motzer RJ. Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin. J Clin Oncol. 1997 Jul;15(7):2553-8. link to original article contains dosing details in manuscript PubMed
  2. Bajorin DF, Sarosdy MF, Pfister DG, Mazumdar M, Motzer RJ, Scher HI, Geller NL, Fair WR, Herr H, Sogani P, Sheinfeld J, Russo P, Vlamis V, Carey R, Vogelzang NJ, Crawford ED, Bosl GJ. Randomized trial of etoposide and cisplatin versus etoposide and carboplatin in patients with good-risk germ cell tumors: a multiinstitutional study. J Clin Oncol. 1993 Apr;11(4):598-606. link to original article PubMed
    1. Update: Xiao H, Mazumdar M, Bajorin DF, Sarosdy M, Vlamis V, Spicer J, Ferrara J, Bosl GJ, Motzer RJ. Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin. J Clin Oncol. 1997 Jul;15(7):2553-8. link to original article contains dosing details in manuscript PubMed
  3. Retrospective: Kondagunta GV, Bacik J, Bajorin D, Dobrzynski D, Sheinfeld J, Motzer RJ, Bosl GJ. Etoposide and cisplatin chemotherapy for metastatic good-risk germ cell tumors. J Clin Oncol. 2005 Dec 20;23(36):9290-4. link to original article contains dosing details in manuscript PubMed

M-TIP

M-TIP: Methotrexate, Taxol (Paclitaxel), Ifosfamide, Platinol (Cisplatin)

Regimen

Study Evidence
Pectasides et al. 2008a Phase 2

Chemotherapy

Supportive therapy

4 cycles

References

  1. Pectasides D, Pectasides E, Papaxoinis G, Xiros N, Kamposioras K, Tountas N, Economopoulos T. Methotrexate, paclitaxel, ifosfamide, and cisplatin in poor-risk nonseminomatous germ cell tumors. Urol Oncol. 2010 Nov-Dec;28(6):617-23. Epub 2008 Dec 25. link to original article PubMed

PVeBV

PVeBV: Platinol (Cisplatin), Velban (Vinblastine), Bleomycin, Vepesid (Etoposide)
VBEP: Vinblastine, Bleomycin, Etoposide, Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Chevreau et al. 1993 NR in abstract Phase 3 (C) PVeBV, then PEC with auto HSCT Did not meet efficacy endpoints of CR rate/OS

Chemotherapy

References

  1. Chevreau C, Droz JP, Pico JL, Biron P, Kerbrat P, Cure H, Héron JF, Chevallier B, Fargeot P, Kramar A, Bouzy J. Early intensified chemotherapy with autologous bone marrow transplantation in first line treatment of poor risk non-seminomatous germ cell tumours: preliminary results of a French randomized trial. Eur Urol. 1993;23(1):213-7. link to original article PubMed
    1. Update: Droz JP, Kramar A, Biron P, Pico JL, Kerbrat P, Pény J, Curé H, Chevreau C, Théodore C, Bouzy J, Culine S; Genito-Urinary Group of the French Federation of Cancer Centers. Failure of high-dose cyclophosphamide and etoposide combined with double-dose cisplatin and bone marrow support in patients with high-volume metastatic nonseminomatous germ-cell tumours: mature results of a randomised trial. Eur Urol. 2007 Mar;51(3):739-46. Epub 2006 Oct 27. link to original article PubMed

VIP

VIP: Vepesid (Etoposide), Ifosfamide, Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Nichols et al. 1998 (ECOG E3887) 1987-1992 Phase 3 (E-switch-ic) BEP Did not meet efficacy endpoints

Chemotherapy

Supportive therapy

  • Mesna (Mesnex) 120 mg/m2 IV slow push once on day 1 given before Ifosfamide (Ifex), then 1200 mg/m2/day IV continuous infusion over 120 hours (though not clearly specified in Nichols et al. 1998, based on its use with ifosfamide, it is assumed that the mesna dose was 1200 mg/m2/day)
  • Normal saline 100 mL/hour IV over 12 hours once per day on days 1 to 5, prior to Cisplatin (Platinol)
  • Normal saline 100 mL/hour IV throughout the 5 day course of Cisplatin (Platinol), ending 6 hours after each cycle's last cisplatin dose
  • G-CSF (type not specified) 5 mcg/kg SC once per day on days 7 to 16

21-day cycle for 4 cycles

References

  1. ECOG E3887: Nichols CR, Catalano PJ, Crawford ED, Vogelzang NJ, Einhorn LH, Loehrer PJ. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol. 1998 Apr;16(4):1287-93. link to original article contains dosing details in manuscript PubMed
    1. Update: Hinton S, Catalano PJ, Einhorn LH, Nichols CR, David Crawford E, Vogelzang N, Trump D, Loehrer PJ Sr. Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors: final analysis of an intergroup trial. Cancer. 2003 Apr 15;97(8):1869-75. link to original article PubMed

Relapsed or refractory, salvage therapy

Carboplatin & Etoposide (CE), then auto HSCT

Regimen

Study Evidence
Nichols et al. 1989 Phase 1/2
Einhorn et al. 2007a Retrospective

Note: the doses here are the ones from the retrospective NEJM article, not from the prospective phase I/II trial. Some patients had salvage VeIP prior to high-dose therapy; others proceeded directly with this regimen as their first salvage treatment.

Chemotherapy

  • Carboplatin (Paraplatin) 700 mg/m2 IV once per day on days -5, -4, -3
  • Etoposide (Vepesid) 750 mg/m2 IV once per day on days -5, -4, -3
  • At least 1 million CD34+ cells per kilogram of body weight was needed for each cycle of chemotherapy.

2 cycles, with the second cycle starting after "recovery of granulocyte and platelet counts"

Subsequent treatment

  • "Most patients" who had CR/PR after two cycles of therapy received etoposide consolidation

References

  1. Nichols CR, Tricot G, Williams SD, van Besien K, Loehrer PJ, Roth BJ, Akard L, Hoffman R, Goulet R, Wolff SN, Giannone L, Greer J, Einhorn LH, Jansen J. Dose-intensive chemotherapy in refractory germ cell cancer--a phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation. J Clin Oncol. 1989 Jul;7(7):932-9. link to original article PubMed
  2. Retrospective: Einhorn LH, Williams SD, Chamness A, Brames MJ, Perkins SM, Abonour R. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med. 2007 Jul 26;357(4):340-8. link to original article contains dosing details in manuscript PubMed

Cisplatin & Epirubicin

CIS-EPI: CISplatin, EPIrubicin

Regimen

Study Evidence
Bedano et al. 2006 Phase 2

Chemotherapy

Supportive therapy

21-day cycle for up to 4 cycles

References

  1. Bedano PM, Brames MJ, Williams SD, Juliar BE, Einhorn LH. Phase II study of cisplatin plus epirubicin salvage chemotherapy in refractory germ cell tumors. J Clin Oncol. 2006 Dec 1;24(34):5403-7. link to original article contains dosing details in manuscript PubMed

GIP

GIP: Gemcitabine, Ifosfamide, Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence
Fizazi et al. 2014 (GIP-TG) 2004-2009 Phase 2

Chemotherapy

References

  1. GIP-TG: Fizazi K, Gravis G, Flechon A, Geoffrois L, Chevreau C, Laguerre B, Delva R, Eymard JC, Rolland F, Houede N, Laplanche A, Burcoveanu D, Culine S. Combining gemcitabine, cisplatin, and ifosfamide (GIP) is active in patients with relapsed metastatic germ-cell tumors (GCT): a prospective multicenter GETUG phase II trial. Ann Oncol. 2014 May;25(5):987-91. Epub 2014 Mar 4. link to original article PubMed NCT00127049

Ifosfamide & Paclitaxel

TI: Taxol (Paclitaxel) & Ifosfamide

Regimen

Study Evidence
Kondagunta et al. 2007 Phase 2

Chemotherapy

Supportive therapy

14-day cycle for 2 cycles; leukapheresis on days 11 to 13 (done on cycle 1, and then only if needed on cycle 2 to have at least 6 x 106 CD34+ cells/kg body weight in peripheral blood stem cells)

Subsequent treatment

References

  1. Kondagunta GV, Bacik J, Sheinfeld J, Bajorin D, Bains M, Reich L, Deluca J, Budnick A, Ishill N, Mazumdar M, Bosl GJ, Motzer RJ. Paclitaxel plus Ifosfamide followed by high-dose carboplatin plus etoposide in previously treated germ cell tumors. J Clin Oncol. 2007 Jan 1;25(1):85-90. Erratum in: J Clin Oncol. 2007 May 20;25(15):2149. link to original article contains dosing details in manuscript PubMed
    1. Update: Feldman DR, Sheinfeld J, Bajorin DF, Fischer P, Turkula S, Ishill N, Patil S, Bains M, Reich LM, Bosl GJ, Motzer RJ. TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis. J Clin Oncol. 2010 Apr 1;28(10):1706-13. Epub 2010 Mar 1. Erratum in: J Clin Oncol. 2010 Dec 1;28(34):5126. link to original article link to PMC article PubMed

TIP

TIP: Taxol (Paclitaxel), Ifosfamide, Platinol (Cisplatin)

Regimen variant #1, 175/6000/100

Study Evidence
Kurobe et al. 2014 Phase 2

Chemotherapy

Supportive therapy

21-day cycle for 4 cycles


Regimen variant #2, 250/6000/100

Study Evidence
Kondagunta et al. 2005 Phase 2

Chemotherapy

Supportive therapy

21-day cycle for 4 cycles

References

  1. Kondagunta GV, Bacik J, Donadio A, Bajorin D, Marion S, Sheinfeld J, Bosl GJ, Motzer RJ. Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. J Clin Oncol. 2005 Sep 20;23(27):6549-55. link to original article contains dosing details in manuscript PubMed
  2. Kurobe M, Kawai K, Oikawa T, Ichioka D, Kandori S, Takaoka E, Kojima T, Joraku A, Suetomi T, Miyazaki J, Nishiyama H. Paclitaxel, ifosfamide, and cisplatin (TIP) as salvage and consolidation chemotherapy for advanced germ cell tumor. J Cancer Res Clin Oncol. 2015 Jan;141(1):127-33. Epub 2014 Jul 26. link to original article link to PMC article contains dosing details in manuscript PubMed
  3. Alliance A031102: NCT02375204

VeIP

VeIP: Velban (Vinblastine), Ifosfamide, Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence
Loehrer et al. 1988 1983-1986 Phase 2 (RT)
Loehrer et al. 1998 1984-1989 Phase 2

Patients in Loehrer et al. 1998 had previously received cisplatin & etoposide based combination chemotherapy.

Chemotherapy

Supportive therapy

  • Mesna (Mesnex) 400 mg/m2 IV bolus on day 1 prior to first dose of Ifosfamide (Ifex), then 1200 mg/m2/day IV continuous infusion over 120 hours (total dose per cycle: 6400 mg/m2)
  • Normal saline 100 mL/hour IV continuous infusion over 120 hours, started on day 1

21-day cycle for 4 cycles

References

  1. Loehrer PJ Sr, Lauer R, Roth BJ, Williams SD, Kalasinski LA, Einhorn LH. Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Intern Med. 1988 Oct 1;109(7):540-6. link to original article PubMed
  2. Loehrer PJ Sr, Gonin R, Nichols CR, Weathers T, Einhorn LH. Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor. J Clin Oncol. 1998 Jul;16(7):2500-4. link to original article contains dosing details in manuscript PubMed

VIP

VIP: Vepesid (Etoposide), Ifosfamide, Platinol (Cisplatin)
PEI: Platinol (Cisplatin), Etoposide, Ifosfamide

Regimen variant #1, 1 cycle

Study Years of enrollment Evidence Comparator Comparative Efficacy
Lorch et al. 2007 1999-2004 Phase 3 (C) VIP x 3, then CEC with auto HSCT Did not meet primary endpoint of EFS12

Chemotherapy

One course

Subsequent treatment


Regimen variant #2, 4 cycles

Study Years of enrollment Evidence Comparator Comparative Efficacy
Loehrer et al. 1986 1983-1984 Non-randomized (RT)
Pico et al. 2005 (IT 94) 1994-2001 Phase 3 (C) VIP x 3, then CarboPEC with auto HSCT Did not meet primary endpoint of EFS

Chemotherapy

4 cycles

References

  1. Loehrer PJ Sr, Einhorn LH, Williams SD. VP-16 plus ifosfamide plus cisplatin as salvage therapy in refractory germ cell cancer. J Clin Oncol. 1986 Apr;4(4):528-36. link to original article PubMed
  2. IT 94: Pico JL, Rosti G, Kramar A, Wandt H, Koza V, Salvioni R, Theodore C, Lelli G, Siegert W, Horwich A, Marangolo M, Linkesch W, Pizzocaro G, Schmoll HJ, Bouzy J, Droz JP, Biron P; Genito-Urinary Group of the French Federation of Cancer Centers; EBMT. A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours. Ann Oncol. 2005 Jul;16(7):1152-9. Epub 2005 May 31. link to original article PubMed
  3. Lorch A, Kollmannsberger C, Hartmann JT, Metzner B, Schmidt-Wolf IG, Berdel WE, Weissinger F, Schleicher J, Egerer G, Haas A, Schirren R, Beyer J, Bokemeyer C, Rick O; German Testicular Cancer Study Group. Single versus sequential high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: a prospective randomized multicenter trial of the German Testicular Cancer Study Group. J Clin Oncol. 2007 Jul 1;25(19):2778-84. link to original article PubMed
    1. Update: Lorch A, Kleinhans A, Kramar A, Kollmannsberger CK, Hartmann JT, Bokemeyer C, Rick O, Beyer J. Sequential versus single high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: long-term results of a prospective randomized trial. J Clin Oncol. 2012 Mar 10;30(8):800-5. Epub 2012 Jan 30. link to original article PubMed

Consolidation after salvage therapy

Carboplatin & Etoposide (CE), then auto HSCT

TI-CE: Taxol (Paclitaxel), Ifosfamide, Carboplatin, Etoposide

Regimen

Study Evidence
Kondagunta et al. 2007 Phase 2

Preceding treatment

Chemotherapy

Supportive therapy

  • Peripheral blood stem cell support (at least 2 x 106 CD34+ cells/kg body weight per infusion) on day 5, 48 hours after carboplatin & etoposide (stem cells were infused each cycle)

14- to 21-day cycle for 3 cycles

References

  1. Kondagunta GV, Bacik J, Sheinfeld J, Bajorin D, Bains M, Reich L, Deluca J, Budnick A, Ishill N, Mazumdar M, Bosl GJ, Motzer RJ. Paclitaxel plus Ifosfamide followed by high-dose carboplatin plus etoposide in previously treated germ cell tumors. J Clin Oncol. 2007 Jan 1;25(1):85-90. Erratum in: J Clin Oncol. 2007 May 20;25(15):2149. link to original article contains dosing details in manuscript PubMed

Etoposide monotherapy

Regimen

Study Evidence
Nichols et al. 1989 Phase 1/2
Einhorn et al. 2007a Retrospective

Preceding treatment

Chemotherapy

28-day cycle for 3 cycles

References

  1. Nichols CR, Tricot G, Williams SD, van Besien K, Loehrer PJ, Roth BJ, Akard L, Hoffman R, Goulet R, Wolff SN, Giannone L, Greer J, Einhorn LH, Jansen J. Dose-intensive chemotherapy in refractory germ cell cancer--a phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation. J Clin Oncol. 1989 Jul;7(7):932-9. link to original article PubMed
  2. Retrospective: Einhorn LH, Williams SD, Chamness A, Brames MJ, Perkins SM, Abonour R. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med. 2007 Jul 26;357(4):340-8. link to original article contains dosing details in manuscript PubMed

Subsequent lines of therapy

Etoposide monotherapy

Regimen

Study Evidence
Miller & Einhorn 1990 Phase 2

Chemotherapy

Continued indefinitely

References

  1. Miller JC, Einhorn LH. Phase II study of daily oral etoposide in refractory germ cell tumors. Semin Oncol. 1990 Feb;17(1 Suppl 2):36-9. PubMed

GemOx

GemOx: GEMcitabine & OXaliplatin

Regimen variant #1, 2000/130

Study Years of enrollment Evidence
Pectasides et al. 2004 1999-2002 Phase 2
Kollmannsberger et al. 2004 2001-2003 Phase 2

Chemotherapy

Supportive therapy

21-day cycle for up to 6 cycles


Regimen variant #2, 2500/130

Study Evidence
De Giorgi et al. 2006 Phase 2, <20 pts

Chemotherapy

21-day cycles

References

  1. Kollmannsberger C, Beyer J, Liersch R, Schoeffski P, Metzner B, Hartmann JT, Rick O, Stengele K, Hohloch K, Spott C, Kanz L, Bokemeyer C; German Testicular Cancer Study Group. Combination chemotherapy with gemcitabine plus oxaliplatin in patients with intensively pretreated or refractory germ cell cancer: a study of the German Testicular Cancer Study Group. J Clin Oncol. 2004 Jan 1;22(1):108-14. link to original article PubMed
  2. Pectasides D, Pectasides M, Farmakis D, Aravantinos G, Nikolaou M, Koumpou M, Gaglia A, Kostopoulou V, Mylonakis N, Skarlos D. Gemcitabine and oxaliplatin (GEMOX) in patients with cisplatin-refractory germ cell tumors: a phase II study. Ann Oncol. 2004 Mar;15(3):493-7. link to original article contains dosing details in manuscript PubMed
  3. De Giorgi U, Rosti G, Aieta M, Testore F, Burattini L, Fornarini G, Naglieri E, Lo Re G, Zumaglini F, Marangolo M. Phase II study of oxaliplatin and gemcitabine salvage chemotherapy in patients with cisplatin-refractory nonseminomatous germ cell tumor. Eur Urol. 2006 Nov;50(5):1032-8. Epub 2006 May 23. link to original article contains dosing details in abstract PubMed

Gemcitabine, Oxaliplatin, Paclitaxel

GOP: Gemcitabine, Oxaliplatin, Paclitaxel

Regimen

Study Years of enrollment Evidence
Bokemeyer et al. 2007 2003-2006 Phase 2

Chemotherapy

Supportive therapy

21-day cycles, given for 2 cycles beyond the best response, up to a maximum of 8 cycles

References

  1. Bokemeyer C, Oechsle K, Honecker F, Mayer F, Hartmann JT, Waller CF, Böhlke I, Kollmannsberger C; German Testicular Cancer Study Group. Combination chemotherapy with gemcitabine, oxaliplatin, and paclitaxel in patients with cisplatin-refractory or multiply relapsed germ-cell tumors: a study of the German Testicular Cancer Study Group. Ann Oncol. 2008 Mar;19(3):448-53. Epub 2007 Nov 15. link to original article contains dosing details in manuscript PubMed

Gemcitabine & Paclitaxel

Regimen variant #1

Study Evidence
Hinton et al. 2002 (ECOG E9897) Phase 2

Chemotherapy

Supportive therapy

28-day cycle for up to 6 cycles


Regimen variant #2

Study Evidence
Einhorn et al. 2007b Phase 2

Chemotherapy

Supportive therapy

28-day cycle for up to 6 cycles

References

  1. ECOG E9897: Hinton S, Catalano P, Einhorn LH, Loehrer PJ Sr, Kuzel T, Vaughn D, Wilding G. Phase II study of paclitaxel plus gemcitabine in refractory germ cell tumors (E9897): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2002 Apr 1;20(7):1859-63. link to original article contains dosing details in manuscript PubMed
  2. Einhorn LH, Brames MJ, Juliar B, Williams SD. Phase II study of paclitaxel plus gemcitabine salvage chemotherapy for germ cell tumors after progression following high-dose chemotherapy with tandem transplant. J Clin Oncol. 2007 Feb 10;25(5):513-6. link to original article contains dosing details in manuscript PubMed

Oxaliplatin & Bevacizumab

Regimen

Study Evidence
Jain et al. 2014 Phase 2

Chemotherapy

Targeted therapy

14-day cycle for a maximum of 14 cycles

References

  1. Jain A, Brames MJ, Vaughn DJ, Einhorn LH. Phase II clinical trial of oxaliplatin and bevacizumab in refractory germ cell tumors. Am J Clin Oncol. 2014 Oct;37(5):450-3. link to original article PubMed

Sunitinib monotherapy

Regimen variant #1

Study Years of enrollment Evidence
Feldman et al. 2010 NR Phase 2, <20 pts

Targeted therapy

42-day cycles


Regimen variant #2

Study Years of enrollment Evidence
Oechsle et al. 2011 2007-2010 Phase 2

Targeted therapy

42-day cycles

References

  1. Feldman DR, Turkula S, Ginsberg MS, Ishill N, Patil S, Carousso M, Bosl GJ, Motzer RJ. Phase II trial of sunitinib in patients with relapsed or refractory germ cell tumors. Invest New Drugs. 2010 Aug;28(4):523-8. link to original article contains dosing details in manuscript PubMed
  2. Oechsle K, Honecker F, Cheng T, Mayer F, Czaykowski P, Winquist E, Wood L, Fenner M, Glaesener S, Hartmann JT, Chi K, Bokemeyer C, Kollmannsberger C; Canadian Urologic Oncology Group; German Testicular Cancer Study Group. Preclinical and clinical activity of sunitinib in patients with cisplatin-refractory or multiply relapsed germ cell tumors: a Canadian Urologic Oncology Group/German Testicular Cancer Study Group cooperative study. Ann Oncol. 2011 Dec;22(12):2654-60. Epub 2011 Mar 17. link to original article PubMed

Statistics

  • Stage I seminoma surveillance relapse - Warde P, Specht L, Horwich A, Oliver T, Panzarella T, Gospodarowicz M, von der Maase H. Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis. J Clin Oncol. 2002 Nov 15;20(22):4448-52. link to original article PubMed

Patient information

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