Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
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</div>
 
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{{#lst:Section editor transclusions|sarcoma}}
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|-
 
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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|}
 
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''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Soft_tissue_sarcoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Soft tissue sarcoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''.
 
−
<br>Note: this page is for subtype-nonspecific soft tissue sarcoma regimens, some subtypes with very few subtype-specific regimens, as well as for sarcomas that are not readily categorized, e.g., alveolar soft part sarcoma. Please see the [[:Category:Soft tissue sarcomas|category page]] for links to other sarcoma types or use one of these links:
 
−
*[[Desmoid tumors]]
 
−
*[[Epithelioid sarcoma]]
 
−
*[[Gastrointestinal stromal tumor|Gastrointestinal stromal tumor (GIST)]]
 
−
*[[Leiomyosarcoma]]
 
−
*[[Liposarcoma]]
 
−
*[[PEComa]]
 
−
*[[Rhabdomyosarcoma]]
 
−
*[[Tenosynovial giant cell tumor|Tenosynovial giant cell tumor (TGCT)]]
 
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{{TOC limit|limit=3}}
 
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=Guidelines=
 
−
==ESMO/EURACAN/GENTURIS==
 
−
*'''2021:''' Gronchi et al. [https://doi.org/10.1016/j.annonc.2021.07.006 Soft tissue and visceral sarcomas: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
−
===Older===
 
−
*'''2018:''' Casali et al. [https://www.esmo.org/Guidelines/Sarcoma-and-GIST/Soft-Tissue-and-Visceral-Sarcomas Soft tissue and visceral sarcomas: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
−
*'''2014:''' [http://annonc.oxfordjournals.org/content/25/suppl_3/iii102.full.pdf+html Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/25210080 PubMed]
 
−
==[https://www.nccn.org/ NCCN]==
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf NCCN Guidelines - Soft Tissue Sarcoma]
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/dfsp.pdf NCCN Guidelines - Dermatofibrosarcoma Protuberans (DFSP)]
 
−
=Neoadjuvant therapy=
 
−
==Epirubicin & Ifosfamide {{#subobject:eeb76b|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:aea2c8|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.2011.37.7218 Gronchi et al. 2012]
 
−
|2002-2007
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(17)30334-0 Gronchi et al. 2017 (ISG-STS 1001)]
 
−
|2011-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|Histotype-tailored therapy
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for ISG-STS 1001 is based on the 2020 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] 1000 mg/m<sup>2</sup> IV every 3 hours to every 4 hours on days 1 to 3
 
−
'''21-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Gronchi et al. 2012: [[Surgery#Surgical_resection|Surgery]], then adjuvant [[#Epirubicin_.26_Ifosfamide|EI]] x 2 versus [[#Observation|no further treatment]]
 
−
*ISG-STS 1001: [[Surgery#Surgical_resection|Surgery]]
 
−
</div></div>
 
−
===References===
 
−
# Gronchi A, Frustaci S, Mercuri M, Martin J, Lopez-Pousa A, Verderio P, Mariani L, Valagussa P, Miceli R, Stacchiotti S, Dei Tos AP, De Paoli A, Longhi A, Poveda A, Quagliuolo V, Comandone A, Casali PG, Picci P; Italian Sarcoma Group; Spanish Sarcoma Group. Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. J Clin Oncol. 2012 Mar 10;30(8):850-6. Epub 2012 Feb 6. [https://doi.org/10.1200/JCO.2011.37.7218 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22312103 PubMed] EudraCT 2004-003979-36
 
−
# '''ISG-STS 1001:''' Gronchi A, Ferrari S, Quagliuolo V, Broto JM, Pousa AL, Grignani G, Basso U, Blay JY, Tendero O, Beveridge RD, Ferraresi V, Lugowska I, Merlo DF, Fontana V, Marchesi E, Donati DM, Palassini E, Palmerini E, De Sanctis R, Morosi C, Stacchiotti S, Bagué S, Coindre JM, Dei Tos AP, Picci P, Bruzzi P, Casali PG. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017 Jun;18(6):812-822. Epub 2017 May 9. [https://doi.org/10.1016/S1470-2045(17)30334-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28499583 PubMed] NCT01710176
 
−
##'''Update:''' Gronchi A, Palmerini E, Quagliuolo V, Martin Broto J, Lopez Pousa A, Grignani G, Brunello A, Blay JY, Tendero O, Diaz Beveridge R, Ferraresi V, Lugowska I, Merlo DF, Fontana V, Marchesi E, Braglia L, Donati DM, Palassini E, Bianchi G, Marrari A, Morosi C, Stacchiotti S, Bagué S, Coindre JM, Dei Tos AP, Picci P, Bruzzi P, Casali PG. Neoadjuvant Chemotherapy in High-Risk Soft Tissue Sarcomas: Final Results of a Randomized Trial From Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) Sarcoma Groups. J Clin Oncol. 2020 Jul 1;38(19):2178-2186. Epub 2020 May 18. [https://doi.org/10.1200/jco.19.03289 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32421444 PubMed]
 
−
==EIA {{#subobject:0608ad|Regimen=1}}==
 
−
EIA: '''<u>E</u>'''toposide, '''<u>I</u>'''fosfamide, '''<u>A</u>'''driamycin (Doxorubicin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:52e303|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://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517819/ Issels et al. 2010 (EORTC 62961/ESHO 95)]
 
−
|1997-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#EIA_.26_regional_hyperthemia_88|EIA & regional hyperthermia]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 1 & 4
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycle for 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Surgery#Surgical_resection|Surgery]], then [[Regimen_classes#Radiotherapy|RT]], then adjuvant [[#EIA_2|EIA]] x 4
 
−
</div></div>
 
−
===References===
 
−
# '''EORTC 62961/ESHO 95:''' Issels RD, Lindner LH, Verweij J, Wust P, Reichardt P, Schem BC, Abdel-Rahman S, Daugaard S, Salat C, Wendtner CM, Vujaskovic Z, Wessalowski R, Jauch KW, Dürr HR, Ploner F, Baur-Melnyk A, Mansmann U, Hiddemann W, Blay JY, Hohenberger P; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group; European Society for Hyperthermic Oncology. Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncol. 2010 Jun;11(6):561-70. Epub 2010 Apr 29. [https://doi.org/10.1016/S1470-2045(10)70071-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517819/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20434400 PubMed] NCT00003052
 
−
## '''Update:''' Issels RD, Lindner LH, Verweij J, Wessalowski R, Reichardt P, Wust P, Ghadjar P, Hohenberger P, Angele M, Salat C, Vujaskovic Z, Daugaard S, Mella O, Mansmann U, Dürr HR, Knösel T, Abdel-Rahman S, Schmidt M, Hiddemann W, Jauch KW, Belka C, Gronchi A; European Organization for the Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group; European Society for Hyperthermic Oncology. Effect of neoadjuvant chemotherapy plus regional hyperthermia on long-term outcomes among patients with localized high-risk soft tissue sarcoma: the EORTC 62961-ESHO 95 randomized clinical trial. JAMA Oncol. 2018 Apr 1;4(4):483-492. [https://jamanetwork.com/journals/jamaoncology/fullarticle/2672386 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885262/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29450452 PubMed]
 
−
=Adjuvant therapy=
 
−
==EIA {{#subobject:8d8ff1|Regimen=1}}==
 
−
EIA: '''<u>E</u>'''toposide, '''<u>I</u>'''fosfamide, '''<u>A</u>'''driamycin (Doxorubicin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6d8a81|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://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517819/ Issels et al. 2010 (EORTC 62961/ESHO 95)]
 
−
|1997-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#EIA_.26_regional_hyperthemia_88|EIA & regional hyperthermia]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Neoadjuvant [[#EIA|EIA]] x 4, then [[Surgery#Surgical_resection|surgery]], then adjuvant RT
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 1 & 4
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 4
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycle for 4 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''EORTC 62961/ESHO 95:''' Issels RD, Lindner LH, Verweij J, Wust P, Reichardt P, Schem BC, Abdel-Rahman S, Daugaard S, Salat C, Wendtner CM, Vujaskovic Z, Wessalowski R, Jauch KW, Dürr HR, Ploner F, Baur-Melnyk A, Mansmann U, Hiddemann W, Blay JY, Hohenberger P; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group; European Society for Hyperthermic Oncology. Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncol. 2010 Jun;11(6):561-70. Epub 2010 Apr 29. [https://doi.org/10.1016/S1470-2045(10)70071-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517819/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20434400 PubMed] NCT00003052
 
−
## '''Update:''' Issels RD, Lindner LH, Verweij J, Wessalowski R, Reichardt P, Wust P, Ghadjar P, Hohenberger P, Angele M, Salat C, Vujaskovic Z, Daugaard S, Mella O, Mansmann U, Dürr HR, Knösel T, Abdel-Rahman S, Schmidt M, Hiddemann W, Jauch KW, Belka C, Gronchi A; European Organization for the Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group; European Society for Hyperthermic Oncology. Effect of neoadjuvant chemotherapy plus regional hyperthermia on long-term outcomes among patients with localized high-risk soft tissue sarcoma: the EORTC 62961-ESHO 95 randomized clinical trial. JAMA Oncol. 2018 Apr 1;4(4):483-492. [https://jamanetwork.com/journals/jamaoncology/fullarticle/2672386 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885262/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29450452 PubMed]
 
−
=Locally advanced or metastatic disease, single-agent regimens=
 
−
==Cisplatin monotherapy {{#subobject:6e93fa|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:2ff0fe|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/S1470-2045(15)70102-6 Blay et al. 2015 (EFC10145)]
 
−
|2008-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cisplatin_.26_Ombrabulin_77|Cisplatin & Ombrabulin]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|-
 
−
|}
 
−
''Note: PFS was very poor in both groups (less than 2 months); the difference was not considered clinically meaningful.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''EFC10145:''' Blay JY, Pápai Z, Tolcher AW, Italiano A, Cupissol D, López-Pousa A, Chawla SP, Bompas E, Babovic N, Penel N, Isambert N, Staddon AP, Saâda-Bouzid E, Santoro A, Franke FA, Cohen P, Le-Guennec S, Demetri GD. Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015 May;16(5):531-40. Epub 2015 Apr 8. [https://doi.org/10.1016/S1470-2045(15)70102-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25864104 PubMed] NCT00699517
 
−
==Dacarbazine monotherapy {{#subobject:62426f|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:2c183b|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/10.1093/oxfordjournals.annonc.a057942 Buesa et al. 1991]
 
−
|1984-1986
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.33.6107 García-Del-Muro et al. 2011]
 
−
|2005-2008
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#Dacarbazine_.26_Gemcitabine|Dacarbazine & Gemcitabine]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Dacarbazine (DTIC)]] 1200 mg/m<sup>2</sup> IV over 20 minutes once on day 1
 
−
====Supportive therapy====
 
−
*'''Buesa et al. 1991:''' Calcium gluconate (10% solution) 5 mL IV every 10 minutes x 3 doses (total of 15 mL) after the start of dacarbazine; 2 additional doses of calcium gluconate (10% solution) 5 mL IV every 10 minutes were given to patients whose systolic blood pressure decreased below 80 mmHg or heart rate more than 160 bpm.
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Buesa JM, Mouridsen HT, van Oosterom AT, Verweij J, Wagener T, Steward W, Poveda A, Vestlev PM, Thomas D, Sylvester R; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. High-dose DTIC in advanced soft-tissue sarcomas in the adult: a phase II study of the EORTC Soft Tissue and Bone Sarcoma Group. Ann Oncol. 1991 Apr;2(4):307-9. [https://doi.org/10.1093/oxfordjournals.annonc.a057942 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1868027 PubMed]
 
−
# García-Del-Muro X, López-Pousa A, Maurel J, Martín J, Martínez-Trufero J, Casado A, Gómez-España A, Fra J, Cruz J, Poveda A, Meana A, Pericay C, Cubedo R, Rubió J, De Juan A, Laínez N, Carrasco JA, de Andrés R, Buesa JM; Spanish Group for Research on Sarcomas. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011 Jun 20;29(18):2528-33. Epub 2011 May 23. [https://doi.org/10.1200/JCO.2010.33.6107 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21606430 PubMed] EudraCT 2005-001709-24
 
−
==Doxorubicin monotherapy {{#subobject:826f82|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 75 mg/m<sup>2</sup> {{#subobject:62faa6|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/10.1002/jso.2930110406 Cruz et al. 1979 (COG 7231A)]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Actinomycin_.26_Melphalan_88|Actinomycin & Melphalan]]<br> 2. [[#Melphalan_.26_Vincristine_88|Melphalan & Vincristine]]<br> 3. [[#Melphalan_.26_1-aminocyclopentanecarboxylic_acid_77|Melphalan & NSC-1026]]
 
−
| style="background-color:#1a9850" |Superior ORR
 
−
|-
 
−
|[https://www.ejcancer.com/article/0277-5379(87)90089-7 Mouridsen et al. 1987 (EORTC 62801)]
 
−
|1980-1983
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Epirubicin_monotherapy|Epirubicin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1995.13.7.1537 Santoro et al. 1995]
 
−
|1985-1990
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Doxorubicin_.26_Ifosfamide|Doxorubicin & Ifosfamide]]<br> 2. [[Stub#CYVADIC|CYVADIC]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of ORR/DOR/OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063236/ Nielsen et al. 1998]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_monotherapy|Epirubicin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2006.09.7717 Lorigan et al. 2007 (EORTC 62971)]
 
−
|rowspan=2|1998-2001
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Ifosfamide_monotherapy|Ifos 3]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|2. [[#Ifosfamide_monotherapy|Ifos 9]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70063-4 Judson et al. 2014 (EORTC 62012)]
 
−
|2003-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin_.26_Ifosfamide|Doxorubicin & Ifosfamide]]; intensified
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(14)00046-X Blay et al. 2014 (CR015769)]
 
−
|2008-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Trabectedin_monotherapy|Trabectedin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2016.67.6684 Ryan et al. 2016 (PICASSO III)]
 
−
|2010-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin_.26_Palifosfamide_77|Doxorubicin & Palifosfamide]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647653/ Tap et al. 2016 (CP15-0806)]
 
−
|2010-2013
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[Soft_tissue_sarcoma_-_historical#Doxorubicin_.26_Olaratumab|Doxorubicin & Olaratumab]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ Seddon et al. 2017 (GeDDiS)]
 
−
|2010-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_Gemcitabine|Docetaxel & Gemcitabine]]
 
−
| style="background-color:#d9ef8b" |Might have superior PFS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(17)30381-9 Tap et al. 2017 (TH CR-406/SARC021)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin_.26_Evofosfamide_77|Doxorubicin & Evofosfamide]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7139275/ Tap et al. 2020 (ANNOUNCE)]
 
−
|2015-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Soft_tissue_sarcoma_-_historical#Doxorubicin_.26_Olaratumab|Doxorubicin & Olaratumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: in EORTC 62801, treatment was given until progression of disease, unacceptable toxicity, or cumulative doxorubicin dosage of 550 mg/m<sup>2</sup>, though the ultimate decision to stop treatment based on cumulative doxorubicin dosage was at the discretion of the treating physician. Patients in CR015769 had translocation-related sarcomas.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV bolus once on day 1
 
−
====Supportive therapy====
 
−
*CP15-0806, optional: [[Dexrazoxane (Zinecard)]] (dose not specified) IV once on day 1
 
−
'''21-day cycle for up to 6 to 8 cycles (see note)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 80 mg/m<sup>2</sup> {{#subobject:fcfa1c|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.1993.11.7.1269 Edmonson et al. 1993]
 
−
|rowspan=2|1987-1990
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Doxorubicin_.26_Ifosfamide|Doxorubicin & Ifosfamide]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior ORR
 
−
|-
 
−
|2. [[#MAC_88|MAC]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 80 mg/m<sup>2</sup> IV bolus once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''COG 7231-A:''' Cruz AB Jr, Thames EA Jr, Aust JB, Metter G, Ramirez G, Fletcher WS, Altman SJ, Frelick RW, Hill GJ 2nd. Combination chemotherapy for soft-tissue sarcomas: a phase III study. J Surg Oncol. 1979;11(4):313-23. [https://doi.org/10.1002/jso.2930110406 link to original article] [https://pubmed.ncbi.nlm.nih.gov/376950 PubMed]
 
−
# '''EORTC 62801:''' Mouridsen HT, Bastholt L, Somers R, Santoro A, Bramwell V, Mulder JH, van Oosterom AT, Buesa J, Pinedo HM, Thomas D, Sylvester R; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. Adriamycin versus epirubicin in advanced soft tissue sarcomas: a randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol. 1987 Oct;23(10):1477-83. [https://www.ejcancer.com/article/0277-5379(87)90089-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3479329 PubMed]
 
−
# Edmonson JH, Ryan LM, Blum RH, Brooks JS, Shiraki M, Frytak S, Parkinson DR. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol. 1993 Jul;11(7):1269-75. [https://doi.org/10.1200/JCO.1993.11.7.1269 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8315424 PubMed]
 
−
# Santoro A, Tursz T, Mouridsen H, Verweij J, Steward W, Somers R, Buesa J, Casali P, Spooner D, Rankin E, Kirkpatrick A, van Glabbeke M, van Oosterom A; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 1995 Jul;13(7):1537-45. [https://doi.org/10.1200/JCO.1995.13.7.1537 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7602342 PubMed]
 
−
# Nielsen OS, Dombernowsky P, Mouridsen H, Crowther D, Verweij J, Buesa J, Steward W, Daugaard S, van Glabbeke M, Kirkpatrick A, Tursz T; [[Study_Groups#EORTC|EORTC]] soft tissue and bone sarcoma group. High-dose epirubicin is not an alternative to standard-dose doxorubicin in the treatment of advanced soft tissue sarcomas: a study of the EORTC soft tissue and bone sarcoma group. Br J Cancer. 1998 Dec;78(12):1634-9. [https://doi.org/10.1038/bjc.1998.735 linkt o original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063236/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/9862576 PubMed]
 
−
# '''Meta-analysis:''' Bramwell VH, Anderson D, Charette ML. Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft-tissue sarcoma: a meta-analysis and clinical practice guideline. Sarcoma. 2000;4(3):103-12. [http://www.hindawi.com/journals/srcm/2000/149793/abs/ link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2395439/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18521288 PubMed]
 
−
# '''EORTC 62971:''' Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, Blay JY; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007 Jul 20;25(21):3144-50. [https://doi.org/10.1200/jco.2006.09.7717 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17634494 PubMed] NCT00003212
 
−
# '''CR015769:''' Blay JY, Leahy MG, Nguyen BB, Patel SR, Hohenberger P, Santoro A, Staddon AP, Penel N, Piperno-Neumann S, Hendifar A, Lardelli P, Nieto A, Alfaro V, Chawla SP. Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas. Eur J Cancer. 2014 Apr;50(6):1137-47. Epub 2014 Feb 7. [https://www.ejcancer.com/article/S0959-8049(14)00046-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24512981 PubMed] NCT00796120
 
−
# '''EORTC 62012:''' Judson I, Verweij J, Gelderblom H, Hartmann JT, Schöffski P, Blay JY, Kerst JM, Sufliarsky J, Whelan J, Hohenberger P, Krarup-Hansen A, Alcindor T, Marreaud S, Litière S, Hermans C, Fisher C, Hogendoorn PC, dei Tos AP, van der Graaf WT; European Organisation and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014 Apr;15(4):415-23. Epub 2014 Mar 5. [https://doi.org/10.1016/S1470-2045(14)70063-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24618336 PubMed] NCT00061984
 
−
# '''CP15-0806:''' Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. Epub 2016 Jun 9. Erratum in: Lancet. 2016 Jul 30;388(10043):464. [https://doi.org/10.1016/S0140-6736(16)30587-6 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647653/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27291997 PubMed] NCT01185964
 
−
# '''PICASSO III:''' Ryan CW, Merimsky O, Agulnik M, Blay JY, Schuetze SM, Van Tine BA, Jones RL, Elias AD, Choy E, Alcindor T, Keedy VL, Reed DR, Taub RN, Italiano A, Garcia Del Muro X, Judson IR, Buck JY, Lebel F, Lewis JJ, Maki RG, Schöffski P. PICASSO III: A Phase III, Placebo-Controlled Study of Doxorubicin With or Without Palifosfamide in Patients With Metastatic Soft Tissue Sarcoma. J Clin Oncol. 2016 Nov 10;34(32):3898-3905. Epub 2016 Sep 30. [https://doi.org/10.1200/JCO.2016.67.6684 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27621408 PubMed] NCT01168791
 
−
# '''TH CR-406/SARC021:''' Tap WD, Papai Z, Van Tine BA, Attia S, Ganjoo KN, Jones RL, Schuetze S, Reed D, Chawla SP, Riedel RF, Krarup-Hansen A, Toulmonde M, Ray-Coquard I, Hohenberger P, Grignani G, Cranmer LD, Okuno S, Agulnik M, Read W, Ryan CW, Alcindor T, Del Muro XFG, Budd GT, Tawbi H, Pearce T, Kroll S, Reinke DK, Schöffski P. Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1089-1103. Epub 2017 Jun 23. [https://doi.org/10.1016/S1470-2045(17)30381-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28651927 PubMed] NCT01440088
 
−
# '''GeDDiS:''' Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Küver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1397-1410. Epub 2017 Sep 4. [https://doi.org/10.1016/S1470-2045(17)30622-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28882536 PubMed] ISRCTN07742377
 
−
# '''ANNOUNCE:''' Tap WD, Wagner AJ, Schöffski P, Martin-Broto J, Krarup-Hansen A, Ganjoo KN, Yen CC, Abdul Razak AR, Spira A, Kawai A, Le Cesne A, Van Tine BA, Naito Y, Park SH, Fedenko A, Pápai Z, Soldatenkova V, Shahir A, Mo G, Wright J, Jones RL; ANNOUNCE Investigators. Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial. JAMA. 2020 Apr 7;323(13):1266-1276. [https://doi.org/10.1001/jama.2020.1707 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7139275/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32259228 PubMed] NCT02451943
 
−
==Epirubicin monotherapy {{#subobject:d976a5|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a1dd30|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://www.ejcancer.com/article/0277-5379(87)90089-7 Mouridsen et al. 1987 (EORTC 62801)]
 
−
|1980-1983
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Doxorubicin_monotherapy|Doxorubicin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV bolus once on day 1
 
−
'''21-day cycle for up to 7 cycles (cumulative epirubicin dosage of 550 mg/m<sup>2</sup>)''' (though the ultimate decision to stop treatment based on cumulative epirubicin dosage was at the discretion of the treating physician)
 
−
</div></div>
 
−
===References===
 
−
# '''EORTC 62801:''' Mouridsen HT, Bastholt L, Somers R, Santoro A, Bramwell V, Mulder JH, van Oosterom AT, Buesa J, Pinedo HM, Thomas D, Sylvester R. Adriamycin versus epirubicin in advanced soft tissue sarcomas: a randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol. 1987 Oct;23(10):1477-83. [https://www.ejcancer.com/article/0277-5379(87)90089-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3479329 PubMed]
 
−
==Ifosfamide monotherapy {{#subobject:88d059|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, short infusion (Ifos 3) {{#subobject:89c8f1|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.2006.09.7717 Lorigan et al. 2007 (EORTC 62971)]
 
−
|rowspan=2|1998-2001
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Doxorubicin_monotherapy|Doxorubicin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|2. [[#Ifosfamide_monotherapy|Ifosfamide]]; Ifos 9
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3, mixed with mesna in 1 liter of normal saline
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup> IV bolus once on day 1, '''given immediately prior to mesna/ifosfamide infusion''', then 1500 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3, given with [[Ifosfamide (Ifex)]], then 1200 mg/m<sup>2</sup> IV twice per day on days 1 to 3, given at 4 and 8 hours after completion of ifosfamide and mesna
 
−
**An alternative is to use oral mesna instead of intravenous: [[Mesna (Mesnex)]] 1200 mg/m<sup>2</sup> PO twice per day on days 1 to 3, given at 2 and 6 hours after completion of ifosfamide and mesna
 
−
*Sodium bicarbonate 150 mmol IV once per day on days 1 to 3
 
−
*Patient with somnolence or other signs of encephalopathy with ifosfamide received methylene blue 50 mg IV every 4 hours until resolution of symptoms. During cycles thereafter, patients would receive methylene blue 50 mg IV every 4 hours, starting 4 hours prior to ifosfamide on day 1, continuing until 72 hours after completion
 
−
'''21-day cycle for up to 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, continuous infusion (Ifos 9) {{#subobject:ad63a|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.2006.09.7717 Lorigan et al. 2007 (EORTC 62971)]
 
−
|rowspan=2|1998-2001
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Doxorubicin_monotherapy|Doxorubicin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|2. [[#Ifosfamide_monotherapy|Ifosfamide]]; Ifos 3
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1, '''given with mesna''' (total dose per cycle: 9000 mg/m<sup>2</sup>)
 
−
**Each day's dose is mixed with mesna in 3 liters of normal saline
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup> IV bolus once on day 1, '''immediately prior to mesna/ifosfamide infusion''', then 3000 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, starting on day 1, given with [[Ifosfamide (Ifex)]], then 1800 mg/m<sup>2</sup> IV over 12 hours once on day 4, starting after completion of ifosfamide and mesna
 
−
**An alternative is to use oral mesna instead of intravenous: [[Mesna (Mesnex)]] 1200 mg/m<sup>2</sup> PO three times on day 4, given 0, 2, and 6 hours after completion of ifosfamide and mesna
 
−
*Sodium bicarbonate 150 mmol IV once per day on days 1 to 3
 
−
*Patient with somnolence or other signs of encephalopathy with ifosfamide received methylene blue 50 mg IV every 4 hours until resolution of symptoms. During cycles thereafter, patients would receive methylene blue 50 mg IV every 4 hours, starting 4 hours prior to ifosfamide on day 1, continuing until 72 hours after completion
 
−
'''21-day cycle for up to 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3 {{#subobject:210d2d|Variant=1}}===
 
−
{| class="wikitable sortable" 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.ejcancer.com/article/S0959-8049(02)00491-4 van Oosterom et al. 2002]
 
−
|1992-1994
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 3, dissolved in 125 mL sterile water per 1000 mg of ifosfamide, mixed with mesna in an additional 1 liter of dextrose/saline
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup> IV bolus once on day 1, '''immediately prior to mesna/ifosfamide infusion''', then 1500 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3, '''given with [[Ifosfamide (Ifex)]]''', then 500 mg/m<sup>2</sup> IV twice per day on days 1 to 3, '''given at 4 and 8 hours after completion of ifosfamide and mesna'''
 
−
*"[[:Category:Emesis_prevention|Antiemetics]] were prescribed according to local conventions"
 
−
*1 liter of fluid PO twice per day on days 1 to 3, taken 4 and 8 hours after completion of ifosfamide and mesna
 
−
'''21-day cycle for at least 2 cycles, except in cases of rapid disease progression'''
 
−
</div></div>
 
−
===References===
 
−
# van Oosterom AT, Mouridsen HT, Nielsen OS, Dombernowsky P, Krzemieniecki K, Judson I, Svancarova L, Spooner D, Hermans C, Van Glabbeke M, Verweij J; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. Results of randomised studies of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) with two different ifosfamide regimens in first- and second-line chemotherapy in advanced soft tissue sarcoma patients. Eur J Cancer. 2002 Dec;38(18):2397-406 [https://www.ejcancer.com/article/S0959-8049(02)00491-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12460784 PubMed] content property of [http://hemonc.org HemOnc.org]
 
−
# '''EORTC 62971:''' Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, Blay JY; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007 Jul 20;25(21):3144-50. [https://doi.org/10.1200/jco.2006.09.7717 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17634494 PubMed] NCT00003212
 
−
==Pazopanib monotherapy {{#subobject:644c8f|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:332a64|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(12)60651-5 van der Graaf et al. 2012 (PALETTE)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Soft_tissue_sarcoma_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 4.6 vs 1.6 mo<br>(HR 0.31, 95% CI 0.24-0.40)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Pazopanib (Votrient)]] 800 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# '''PALETTE:''' van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Schöffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group; PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879-86. Epub 2012 May 16. [https://doi.org/10.1016/S0140-6736(12)60651-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22595799 PubMed] NCT00753688
 
−
## '''Subgroup analysis:''' Kawai A, Araki N, Hiraga H, Sugiura H, Matsumine A, Ozaki T, Ueda T, Ishii T, Esaki T, Machida M, Fukasawa N. A randomized, double-blind, placebo-controlled, phase III study of pazopanib in patients with soft tissue sarcoma: results from the Japanese subgroup. Jpn J Clin Oncol. 2016 Mar;46(3):248-53. Epub 2016 Feb 10. [https://academic.oup.com/jjco/article/46/3/248/2384950 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4777611/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26864131 PubMed]
 
−
==Regorafenib monotherapy {{#subobject:c9fc2c|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b5ff4e|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/S1470-2045(16)30507-1 Mir et al. 2016 (REGOSARC)]
 
−
|2013-2014
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|[[Soft_tissue_sarcoma_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#1a9850" |Superior PFS
 
−
|-
 
−
|}
 
−
''Note: reported efficacy is for the leiomyosarcoma, synovial sarcoma, and other sarcoma cohorts; there was no significant difference in outcome for the liposarcoma cohort.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''REGOSARC:''' Mir O, Brodowicz T, Italiano A, Wallet J, Blay JY, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, Perrin C, Delcambre C, Liegl-Atzwanger B, Toulmonde M, Dumont S, Ray-Coquard I, Clisant S, Taieb S, Guillemet C, Rios M, Collard O, Bozec L, Cupissol D, Saada-Bouzid E, Lemaignan C, Eisterer W, Isambert N, Chaigneau L, Cesne AL, Penel N. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1732-1742. Epub 2016 Oct 14.  [https://doi.org/10.1016/S1470-2045(16)30507-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27751846 PubMed] NCT01900743
 
−
==Temozolomide monotherapy {{#subobject:5929ed|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 5 out of 28 days {{#subobject:63d3d8|Variant=1}}===
 
−
{| class="wikitable sortable" 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/10.1002/cncr.11730 Talbot et al. 2003]
 
−
|1998-2000
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: patients on study could be reconsented to receive therapy beyond 1 year. Treatment given on an empty stomach, and doses rounded up if needed to next available dosage based on capsule doses.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once on day 1, then 12 hours later, 90 mg/m<sup>2</sup> PO every 12 hours on days 1 to 5 (total of 10 doses per cycle)
 
−
====Supportive therapy====
 
−
*[[:Category:Emesis_prevention|Antiemetics]] "prescribed as clinically indicated by the treating physician"
 
−
'''28-day cycle for up to 13 cycles (1 year)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 6 out of 9 weeks {{#subobject:892d65|Variant=1}}===
 
−
{| class="wikitable sortable" 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/10.1002/cncr.21384 Garcia del Muro et al. 2005]
 
−
|1999-2001
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: Initial dose used in the study was 75 mg/m<sup>2</sup>, but due to lack of toxicity, protocol was amended to use 100 mg/m<sup>2</sup> doses.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Temozolomide (Temodar)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 42, no food 1 hour before and after temozolomide doses
 
−
====Supportive therapy====
 
−
*"[[:Category:Emesis_prevention|Antiemetics]], mainly oral [[Metoclopramide (Reglan)]] and [[Ondansetron (Zofran)]], were prescribed as clinically indicated by the treating physician"
 
−
'''9-week cycle for up to 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Talbot SM, Keohan ML, Hesdorffer M, Orrico R, Bagiella E, Troxel AB, Taub RN. A phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma. Cancer. 2003 Nov 1;98(9):1942-6. [https://doi.org/10.1002/cncr.11730 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14584078 PubMed]
 
−
# Garcia del Muro X, Lopez-Pousa A, Martin J, Buesa JM, Martinez-Trufero J, Casado A, Poveda A, Cruz J, Bover I, Maurel J; Spanish Group for Research on Sarcomas. A phase II trial of temozolomide as a 6-week, continuous, oral schedule in patients with advanced soft tissue sarcoma: a study by the Spanish Group for Research on Sarcomas. Cancer. 2005 Oct 15;104(8):1706-12. [https://doi.org/10.1002/cncr.21384 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16134177 PubMed]
 
−
==Trabectedin monotherapy {{#subobject:cfc3ed|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 1.2 mg/m<sup>2</sup> {{#subobject:33de2b|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/S1470-2045(15)70098-7 Kawai et al. 2015]
 
−
|2012-2014
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|[[Soft_tissue_sarcoma_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#1a9850" |Superior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Trabectedin (Yondelis)]] 1.2 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 1.5 mg/m<sup>2</sup> {{#subobject:33523b|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/j.annonc.2021.04.014 Le Cesne et al. 2021 (T-SAR)]
 
−
|2015
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Soft_tissue_sarcoma_-_null_regimens#Best_supportive_care|Best supportive care]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 3.1 vs 1.5 mo<br>(HR 0.39, 95% CI 0.24-0.64)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Trabectedin (Yondelis)]] 1.5 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, Morioka H, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Tanase T, Hasegawa T, Takahashi S. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol. 2015 Apr;16(4):406-16. Epub 2015 Mar 18. [https://doi.org/10.1016/S1470-2045(15)70098-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25795406 PubMed] JapicCTI-121850
 
−
# '''T-SAR:''' Le Cesne A, Blay JY, Cupissol D, Italiano A, Delcambre C, Penel N, Isambert N, Chevreau C, Bompas E, Bertucci F, Chaigneau L, Piperno-Neumann S, Salas S, Rios M, Guillemet C, Bay JO, Ray-Coquard I, Haddag L, Bonastre J, Kapso R, Fraslin A, Bouvet N, Mir O, Foulon S. A randomized phase III trial comparing trabectedin to best supportive care in patients with pre-treated soft tissue sarcoma: T-SAR, a French Sarcoma Group trial. Ann Oncol. 2021 Aug;32(8):1034-1044. Epub 2021 Apr 29. [https://doi.org/10.1016/j.annonc.2021.04.014 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33932507/ PubMed] NCT02672527
 
  
−
=Locally advanced or metastatic disease, combination regimens=
 
−
==Dacarbazine & Doxorubicin {{#subobject:9085a9|Regimen=1}}==
 
−
AD: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>D</u>'''acarbazine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a9a5c2|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.1987.5.6.851 Baker et al. 1987 (SWOG S7613)]
 
−
|1976-1979
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Cyclophosphamide.2C_Dacarbazine.2C_Doxorubicin_99|AD & Cyclophosphamide]]<br> 2. [[#Dacarbazine.2C_Dactinomycin.2C_Doxorubicin_99|AD & Dactinomycin]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of RR/OS
 
−
|-
 
−
|[https://academic.oup.com/jnci/article-abstract/83/13/926/988180 Zalupski et al. 1991]
 
−
|1980-1986
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Dacarbazine_.26_Doxorubicin|Dacarbazine & Doxorubicin]]; CI
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS50%
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1993.11.7.1276 Antman et al. 1993]
 
−
|1987-1989
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#MAID|MAID]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>In Antman et al. 1993, although the experimental arm seemed to have superior TTP, this arm seemed to have superior OS.''<br>
 
−
''Here for historic purposes.''
 
−
====Chemotherapy====
 
−
*[[Dacarbazine (DTIC)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''SWOG S7613:''' Baker LH, Frank J, Fine G, Balcerzak SP, Stephens RL, Stuckey WJ, Rivkin S, Saiki J, Ward JH. Combination chemotherapy using adriamycin, DTIC, cyclophosphamide, and actinomycin D for advanced soft tissue sarcomas: a randomized comparative trial: a phase III, Southwest Oncology Group Study (7613). J Clin Oncol. 1987 Jun;5(6):851-61. [https://doi.org/10.1200/JCO.1987.5.6.851 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3295129 PubMed]
 
−
# Zalupski M, Metch B, Balcerzak S, Fletcher WS, Chapman R, Bonnet JD, Weiss GR, Ryan J, Benjamin RS, Baker LH; [[Study_Groups#SWOG|SWOG]]. Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: a Southwest Oncology Group study. J Natl Cancer Inst. 1991 Jul 3;83(13):926-32. [https://academic.oup.com/jnci/article-abstract/83/13/926/988180 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2067035 PubMed]
 
−
# Antman K, Crowley J, Balcerzak SP, Rivkin SE, Weiss GR, Elias A, Natale RB, Cooper RM, Barlogie B, Trump DL, Doroshow JH, Aisner J, Pugh RP, Weiss RB, Cooper BA, Clamond GH, Baker LH. An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol. 1993 Jul;11(7):1276-85. [https://doi.org/10.1200/JCO.1993.11.7.1276 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8315425 PubMed]
 
−
==Dacarbazine & Gemcitabine {{#subobject:cd9068|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9aaddf|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.2010.33.6107 García-Del-Muro et al. 2011]
 
−
|2005-2008
 
−
| style="background-color:#ffffbe" |Randomized Phase 2, <20 pts in this subgroup (E-esc)
 
−
|[[#Dacarbazine_monotherapy|Dacarbazine]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Dacarbazine (DTIC)]] 500 mg/m<sup>2</sup> IV over 20 minutes once on day 1, '''given second'''
 
−
*[[Gemcitabine (Gemzar)]] 1800 mg/m<sup>2</sup> IV at fixed dosed rate over 3 hours once on day 1, '''given first'''
 
−
'''14-day cycle for at least 12 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# García-Del-Muro X, López-Pousa A, Maurel J, Martín J, Martínez-Trufero J, Casado A, Gómez-España A, Fra J, Cruz J, Poveda A, Meana A, Pericay C, Cubedo R, Rubió J, De Juan A, Laínez N, Carrasco JA, de Andrés R, Buesa JM; Spanish Group for Research on Sarcomas. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011 Jun 20;29(18):2528-33. Epub 2011 May 23. [https://doi.org/10.1200/JCO.2010.33.6107 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21606430 PubMed] EudraCT 2005-001709-24
 
−
==Docetaxel & Gemcitabine {{#subobject:1e718f|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:2898f9|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://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ Seddon et al. 2017 (GeDDiS)]
 
−
|2010-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Doxorubicin_monotherapy|Doxorubicin]]
 
−
| style="background-color:#fee08b" |Might have inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 8, '''given second'''
 
−
*[[Gemcitabine (Gemzar)]] 675 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8, '''given first'''
 
−
====Supportive therapy====
 
−
*[[Dexamethasone (Decadron)]] 8 mg PO twice per day on days 7 to 9 (the day before, the day of, and day after [[Docetaxel (Taxotere)]])
 
−
*Patients could receive diuretics at physician discretion for peripheral edema related to docetaxel
 
−
*One of the following growth factors (varies depending on reference):
 
−
**[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 150 mcg/m<sup>2</sup> (dose rounded to 300 or 480 mcg) SC once per day on days 9 to 15 as primary neutropenia prophylaxis; could be stopped before day 15 if ANC greater than 1200/uL on two separate measurements
 
−
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once on either day 9 or 10
 
−
'''21-day cycle for 6 to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''GeDDiS:''' Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Küver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1397-1410. Epub 2017 Sep 4. [https://doi.org/10.1016/S1470-2045(17)30622-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28882536 PubMed] ISRCTN07742377
 
−
==Doxorubicin & Ifosfamide {{#subobject:e28770|Regimen=1}}==
 
−
AIM: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>I</u>'''fosfamide, '''<u>M</u>'''esna
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 50/5000 {{#subobject:78d03a|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.2000.18.14.2676 Le Cesne et al. 2000 (EORTC 62903)]
 
−
|1992-1995
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin_.26_Ifosfamide|AIM]]; 75/5000
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 5-day course, lower dose doxorubicin - AI 75/10,000 {{#subobject:9c1374|Variant=1}}===
 
−
{| class="wikitable sortable" 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/10.1097/00000421-199806000-00025 Patel et al. 1998]
 
−
|1995-1996
 
−
| style="background-color:#ffffbe" |Pilot, <20 patients reported
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 75 mg/m<sup>2</sup>)
 
−
*[[Ifosfamide (Ifex)]] 2000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] 400 mg/m<sup>2</sup> IV once on day 1, given simultaneously with the first dose of [[Ifosfamide (Ifex)]], then 1200 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours
 
−
**Each day's dose is given in 2 liters of D5W with 100 mEq/L sodium acetate, 20 mEq/L potassium acetate, and 4 mEq/L magnesium sulfate
 
−
*If febrile neutropenia occurs, [[:Category:Granulocyte colony-stimulating factors|G-CSF]] is used in subsequent cycles
 
−
'''21-day cycle for up to 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 4-day course, higher dose doxorubicin - AI 90/10,000 {{#subobject:2fd91c|Variant=1}}===
 
−
{| class="wikitable sortable" 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/10.1097/00000421-199806000-00025 Patel et al. 1998]
 
−
|1995-1996
 
−
| style="background-color:#ffffbe" |Pilot, <20 patients reported
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 90 mg/m<sup>2</sup>)
 
−
*[[Ifosfamide (Ifex)]] 2500 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 4
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] 500 mg/m<sup>2</sup> IV once on day 1, given simultaneously with the first dose of [[Ifosfamide (Ifex)]], then 1500 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours
 
−
***Each day's dose is given in 2 liters of D5W with 100 mEq/L sodium acetate, 20 mEq/L potassium acetate, and 4 mEq/L magnesium sulfate
 
−
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 5 mcg/kg (dose rounded to 300 or 480 mcg) SC once per day, starting on day 5, given until ANC is at least 10,000/uL
 
−
'''21-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Patel SR, Vadhan-Raj S, Burgess MA, Plager C, Papadopolous N, Jenkins J, Benjamin RS. Results of two consecutive trials of dose-intensive chemotherapy with doxorubicin and ifosfamide in patients with sarcomas. Am J Clin Oncol. 1998 Jun;21(3):317-21. [https://doi.org/10.1097/00000421-199806000-00025 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9626808 PubMed]
 
−
# '''EORTC 62903:''' Le Cesne A, Judson I, Crowther D, Rodenhuis S, Keizer HJ, Van Hoesel Q, Blay JY, Frisch J, Van Glabbeke M, Hermans C, Van Oosterom A, Tursz T, Verweij J. Randomized phase III study comparing conventional-dose doxorubicin plus ifosfamide versus high-dose doxorubicin plus ifosfamide plus recombinant human granulocyte-macrophage colony-stimulating factor in advanced soft tissue sarcomas: A trial of the European Organisation for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 2000 Jul;18(14):2676-84. [https://doi.org/10.1200/JCO.2000.18.14.2676 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10894866 PubMed]
 
−
==Doxorubicin, Ifosfamide, RT {{#subobject:e36470|Regimen=1}}==
 
−
AIM & RT: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>I</u>'''fosfamide, '''<u>M</u>'''esna, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:0acb5d|Variant=1}} ===
 
−
{| class="wikitable sortable" 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/pmc6946838/ Spunt et al. 2019 (COG ARST0332 Arm D)]
 
−
|2007-2012
 
−
| style="background-color:#91cf61" |Phase 3b
 
−
|-
 
−
|}
 
−
''Note: Regimen details are derived from ClinicalTrials.gov.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 5: 37.5 mg/m<sup>2</sup>/day (maximum dose of 75 mg/day) IV continuous infusion over 48 hours, started on day 1 (total dose per cycle: 75 mg/m<sup>2</sup>)
 
−
**Doses are held when patients are receiving concurrent radiation therapy (for example, held during cycles 2 and 3, if radiation therapy is initiated with cycle 2). The missed doses are then administered in a different cycle, to maintain a total regimen dose of 375 mg/m<sup>2</sup>. If doses are held in 2 of 6 cycles, a doxorubicin-only "Cycle 7" may be given 21 days following cycle 6. 
 
−
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 3
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup> IV over 15 minutes once per day on days 1 to 3, given 15 minutes prior to each dose of [[Ifosfamide (Ifex)]], then at 3 hours, 6 hours, and 9 hours after start of [[Ifosfamide (Ifex)]]
 
−
*Hydration:
 
−
**Before first [[Ifosfamide (Ifex)]] infusion: D5 1/2 NS IV at rate of 200 mL/m<sup>2</sup>/hr IV until urine output > 2 mL/kg/hr
 
−
**With [[Ifosfamide (Ifex)]] infusion: D5 1/2 NS with 10 mEq KCL/L IV at rate of 125 mL/m<sup>2</sup>/hr IV beginning immediately after ifosfamide infusion and continuing until next ifosfamide dose, or until 24 hours after last dose.
 
−
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 5 mcg/kg (max 480 mcg) SC once per day, starting on day 4, given until ANC is at least 2000/uL after nadir. Filgrastim should not be administered within 24 hours of chemotherapy.
 
−
'''21-day cycle for up to 6 cycles'''
 
−
====Radiotherapy====
 
−
*[[External beam radiotherapy]] beginning with cycle 2 (week 4)
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
* Definitive [[Surgery#Surgical_resection|resection]] of primary tumor after recovery from cycle 3 (week 13)
 
−
* Definitive [[Surgery#Surgical_resection|resection]] of residual metastasis after completion of chemotherapy
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Venkatramani R, Anderson JR, Million L, Coffin CM, McCarville B, Randall RL, et al. Risk-based treatment for synovial sarcoma in patients under 30 years of age: Children’s Oncology Group study ARST0332. J Clin Oncol [Internet]. 2015;33(15). [https://doi.org/10.1200/jco.2015.33.15_suppl.10012 link to original abstract] -->
 
−
#'''COG ARST0332:''' Spunt SL, Million L, Chi YY, Anderson J, Tian J, Hibbitts E, Coffin C, McCarville MB, Randall RL, Parham DM, Black JO, Kao SC, Hayes-Jordan A, Wolden S, Laurie F, Speights R, Kawashima E, Skapek SX, Meyer W, Pappo AS, Hawkins DS. A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study. Lancet Oncol. 2020 Jan;21(1):145-161. Epub 2019 Nov 27. [https://doi.org/10.1016/s1470-2045(19)30672-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6946838/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31786124/ PubMed] NCT00346164
 
−
==Epirubicin & Ifosfamide {{#subobject:820f20|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:55e5db|Variant=1}}===
 
−
{| class="wikitable sortable" 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/10.1200/jco.1998.16.4.1438 Reichardt et al. 1998]
 
−
|1993-1996
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 45 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours, started on day 2 (total dose per cycle: 90 mg/m<sup>2</sup>)
 
−
*[[Ifosfamide (Ifex)]] 2500 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 12,500 mg/m<sup>2</sup>)
 
−
**Each day's dose is mixed with mesna in 3 liters of "fluids with electrolytes"
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] 1500 mg/m<sup>2</sup> IV continuous infusion over 120 hours, started on day 1, '''given with [[Ifosfamide (Ifex)]]''' (total dose per cycle: 7500 mg/m<sup>2</sup>)
 
−
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 5 mcg/kg SC once per day on days 6 to 15 or "until recovery of leukocytes"
 
−
*[[Ondansetron (Zofran)]] 8 to 24 mg/day (route not specified) prn nausea
 
−
*[[Dexamethasone (Decadron)]] (dose/schedule not specified) for antiemesis if necessary
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Reichardt P, Tilgner J, Hohenberger P, Dörken B. Dose-intensive chemotherapy with ifosfamide, epirubicin, and filgrastim for adult patients with metastatic or locally advanced soft tissue sarcoma: a phase II study. J Clin Oncol. 1998 Apr;16(4):1438-43. [https://doi.org/10.1200/jco.1998.16.4.1438 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9552049 PubMed]
 
−
==Gemcitabine & Vinorelbine {{#subobject:4dd538|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b605f7|Variant=1}}===
 
−
{| class="wikitable sortable" 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/10.1002/cncr.22609 Dileo et al. 2007]
 
−
|2003-2005
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8
 
−
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV over 10 minutes once per day on days 1 & 8
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Dileo P, Morgan JA, Zahrieh D, Desai J, Salesi JM, Harmon DC, Quigley MT, Polson K, Demetri GD, George S. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: results of a phase II trial. Cancer. 2007 May 1;109(9):1863-9. [https://doi.org/10.1002/cncr.22609 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17385194 PubMed]
 
−
==MAID {{#subobject:71cfab|Regimen=1}}==
 
−
MAID: '''<u>M</u>'''esna, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>I</u>'''fosfamide, '''<u>D</u>'''acarbazine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:156439|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.1993.11.7.1276 Antman et al. 1993]
 
−
|1987-1989
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Dacarbazine_.26_Doxorubicin|AD]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1007/s10637-008-9217-1 Fayette et al. 2009]
 
−
|1994-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[#MAID|MAID]; higher-intensity
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdr282 Bui-Nguyen et al. 2011]
 
−
|2000-2008
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
''<sup>1</sup>In Antman et al. 1993, although this arm seemed to have superior TTP, the control arm seemed to have superior OS.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Ifosfamide (Ifex)]]
 
−
*[[Dacarbazine (DTIC)]]
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]]
 
−
</div></div>
 
−
===References===
 
−
# Antman K, Crowley J, Balcerzak SP, Rivkin SE, Weiss GR, Elias A, Natale RB, Cooper RM, Barlogie B, Trump DL, Doroshow JH, Aisner J, Pugh RP, Weiss RB, Cooper BA, Clamond GH, Baker LH. An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol. 1993 Jul;11(7):1276-85. [https://doi.org/10.1200/JCO.1993.11.7.1276 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8315425 PubMed]
 
−
# Fayette J, Penel N, Chevreau C, Blay JY, Cupissol D, Thyss A, Guillemet C, Rios M, Rolland F, Fargeot P, Bay JO, Mathoulin-Pelissier S, Coindre JM, Bui-Nguyen B. Phase III trial of standard versus dose-intensified doxorubicin, ifosfamide and dacarbazine (MAID) in the first-line treatment of metastatic and locally advanced soft tissue sarcoma. Invest New Drugs. 2009 Oct;27(5):482-9. Epub 2009 Jan 16. [https://doi.org/10.1007/s10637-008-9217-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19148579 PubMed]
 
−
# Bui-Nguyen B, Ray-Coquard I, Chevreau C, Penel N, Bay JO, Coindre JM, Cupissol D, Italiano A, Bonichon F, Lotz JP, Thyss A, Jimenez M, Mathoulin-Pélissier S, Blay JY; GSF-GETO. High-dose chemotherapy consolidation for chemosensitive advanced soft tissue sarcoma patients: an open-label, randomized controlled trial. Ann Oncol. 2012 Mar;23(3):777-84. Epub 2011 Jun 7. [https://doi.org/10.1093/annonc/mdr282 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21652583 PubMed]
 
−
=Dermatofibrosarcoma protuberans, all lines of therapy=
 
−
==Imatinib monotherapy {{#subobject:d700c4|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 400 mg/day {{#subobject:966ba9|Variant=1}}===
 
−
{| class="wikitable sortable" 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/PMC3040044/ Rutkowski et al. 2010 (SWOG S0345)]
 
−
|2005-2006
 
−
| style="background-color:#ffffbe" |Phase 2, <20 pts
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Imatinib (Gleevec)]] 400 mg PO once per day
 
−
'''48-week course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 800 mg/day {{#subobject:7389b7|Variant=1}}===
 
−
{| class="wikitable sortable" 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/PMC3040044/ Rutkowski et al. 2010 (EORTC 62027)]
 
−
|2004-2007
 
−
| style="background-color:#ffffbe" |Phase 2, <20 pts (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Imatinib (Gleevec)]] 400 mg PO twice per day
 
−
'''Continued indefinitely, unless complete (R0) surgical resection became possible'''
 
−
</div></div>
 
−
===References===
 
−
# '''EORTC 62027:''' Rutkowski P, Van Glabbeke M, Rankin CJ, Ruka W, Rubin BP, Debiec-Rychter M, Lazar A, Gelderblom H, Sciot R, Lopez-Terrada D, Hohenberger P, van Oosterom AT, Schuetze SM; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group; [[Study_Groups#SWOG|SWOG]]. Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol. 2010 Apr 1;28(10):1772-9. Epub 2010 Mar 1. [https://doi.org/10.1200/JCO.2009.25.7899 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20194851 PubMed] NCT00085475
 
−
# '''SWOG S0345:''' Rutkowski P, Van Glabbeke M, Rankin CJ, Ruka W, Rubin BP, Debiec-Rychter M, Lazar A, Gelderblom H, Sciot R, Lopez-Terrada D, Hohenberger P, van Oosterom AT, Schuetze SM; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group; [[Study_Groups#SWOG|SWOG]]. Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol. 2010 Apr 1;28(10):1772-9. Epub 2010 Mar 1. [https://doi.org/10.1200/JCO.2009.25.7899 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20194851 PubMed] NCT00084630
 
−
[[Category:Soft tissue sarcoma regimens]]
 
−
[[Category:Disease-specific pages]]
 
−
[[Category:Soft tissue sarcomas]]
 

Latest revision as of 00:13, 18 June 2023

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