Difference between revisions of "Liposarcoma"

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<span id="BackToTop"></span>
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!colspan="2" align="center" style="color:white; font-size:125%; background-color:#08519c"|'''Section editor'''
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<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
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[[#top|Back to Top]]
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|style="background-color:#F0F0F0"|[[File:Elizabethdavis2.jpg|frameless|upright=0.3|center]]
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</div>
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|<big>[[User:Elizabethdavis|Elizabeth J. Davis, MD]]<br>Vanderbilt University<br>Nashville, TN</big><br>[[File:Social-twitter-icon.png|frameless|upright=0.1]] [https://twitter.com/ejdavis25 ejdavis25]
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{{#lst:Editorial board transclusions|sarcoma}}
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''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Liposarcoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''.<br>
−
|}
 
 
Note: these are regimens tested in subtype-specific populations, please see the '''[[Soft_tissue_sarcoma|main soft tissue sarcoma page]]''' for other regimens.
 
Note: these are regimens tested in subtype-specific populations, please see the '''[[Soft_tissue_sarcoma|main soft tissue sarcoma page]]''' for other regimens.
 
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{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
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=All lines of therapy=
+
=Guidelines=
 +
'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
 +
==NCCN==
 +
*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1464 NCCN Guidelines - Soft Tissue Sarcoma].''
 +
=Advanced or metastatic disease, subsequent lines of therapy=
 
==Dacarbazine monotherapy {{#subobject:62426f|Regimen=1}}==
 
==Dacarbazine monotherapy {{#subobject:62426f|Regimen=1}}==
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{| class="wikitable" style="float:right; margin-left: 5px;"
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<div class="toccolours" style="background-color:#eeeeee">
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
===Regimen variant #1, 850 mg/m<sup>2</sup> {{#subobject:f09c3f|Variant=1}}===
 
===Regimen variant #1, 850 mg/m<sup>2</sup> {{#subobject:f09c3f|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%"|Dates 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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016 (E7389-G000-309)]
+
|[https://doi.org/10.1016/S0140-6736(15)01283-0 Schöffski et al. 2016 (E7389-G000-309)]
 
|2011-2013
 
|2011-2013
−
| style="background-color:#1a9851" |Phase III (C)
+
| style="background-color:#1a9851" |Phase 3 (C)
 
|[[#Eribulin_monotherapy|Eribulin]]
 
|[[#Eribulin_monotherapy|Eribulin]]
−
| style="background-color:#fc8d59" |Seems to have inferior OS
+
| style="background-color:#d73027" |Inferior OS<sup>1</sup>
 
|-
 
|-
 
|}
 
|}
 +
''<sup>1</sup>Reported efficacy is based on the 2017 subgroup analysis.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Dacarbazine (DTIC)]] 850 mg/m<sup>2</sup> IV over 20 to 120 minutes once on day 1
 
*[[Dacarbazine (DTIC)]] 850 mg/m<sup>2</sup> IV over 20 to 120 minutes once on day 1
−
 
 
'''21-day cycles'''
 
'''21-day cycles'''
−
 
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #2, 1000 mg/m<sup>2</sup> {{#subobject:4b5552|Variant=1}}===
 
===Regimen variant #2, 1000 mg/m<sup>2</sup> {{#subobject:4b5552|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%"|Dates 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
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|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ Demetri et al. 2015 (ET743-SAR-3007)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ Demetri et al. 2015 (ET743-SAR-3007)]
−
|2011-2015
+
|2011-2013
−
| style="background-color:#1a9851" |Phase III (C)
+
| style="background-color:#1a9851" |Phase 3 (C)
 
|[[#Trabectedin_monotherapy|Trabectedin]]
 
|[[#Trabectedin_monotherapy|Trabectedin]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016 (E7389-G000-309)]
+
|[https://doi.org/10.1016/S0140-6736(15)01283-0 Schöffski et al. 2016 (E7389-G000-309)]
 
|2011-2013
 
|2011-2013
−
| style="background-color:#1a9851" |Phase III (C)
+
| style="background-color:#1a9851" |Phase 3 (C)
 
|[[#Eribulin_monotherapy|Eribulin]]
 
|[[#Eribulin_monotherapy|Eribulin]]
−
| style="background-color:#fc8d59" |Seems to have inferior OS
+
| style="background-color:#d73027" |Inferior OS<sup>1</sup>
 
|-
 
|-
 
|}
 
|}
 +
''<sup>1</sup>Reported efficacy is based on the 2017 subgroup analysis.''<br>
 
''Note: this is listed as a "starting dose" in Demetri et al. 2015, but no adjustment instructions were provided in the manuscript.''
 
''Note: this is listed as a "starting dose" in Demetri et al. 2015, but no adjustment instructions were provided in the manuscript.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Dacarbazine (DTIC)]] 1000 mg/m<sup>2</sup> IV over 20 to 120 minutes once on day 1
 
*[[Dacarbazine (DTIC)]] 1000 mg/m<sup>2</sup> IV over 20 to 120 minutes once on day 1
−
 
 
'''21-day cycles'''
 
'''21-day cycles'''
−
 
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #3, 1200 mg/m<sup>2</sup> {{#subobject:2c183b|Variant=1}}===
 
===Regimen variant #3, 1200 mg/m<sup>2</sup> {{#subobject:2c183b|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%"|Dates 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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016 (E7389-G000-309)]
+
|[https://doi.org/10.1016/S0140-6736(15)01283-0 Schöffski et al. 2016 (E7389-G000-309)]
 
|2011-2013
 
|2011-2013
−
| style="background-color:#1a9851" |Phase III (C)
+
| style="background-color:#1a9851" |Phase 3 (C)
 
|[[#Eribulin_monotherapy|Eribulin]]
 
|[[#Eribulin_monotherapy|Eribulin]]
−
| style="background-color:#fc8d59" |Seems to have inferior OS
+
| style="background-color:#d73027" |Inferior OS<sup>1</sup>
 
|-
 
|-
 
|}
 
|}
 +
''<sup>1</sup>Reported efficacy is based on the 2017 subgroup analysis.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Dacarbazine (DTIC)]] 1200 mg/m<sup>2</sup> IV over 20 minutes once on day 1
 
*[[Dacarbazine (DTIC)]] 1200 mg/m<sup>2</sup> IV over 20 minutes once on day 1
−
 
+
====Supportive therapy====
−
====Supportive medications====
 
 
*'''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.
 
*'''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'''
 
'''21-day cycles'''
−
 
+
</div></div>
 
===References===
 
===References===
−
# '''ET743-SAR-3007:''' Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. [http://jco.ascopubs.org/content/34/8/786.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26371143 PubMed]
+
# '''ET743-SAR-3007:''' Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. [https://doi.org/10.1200/jco.2015.62.4734 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26371143/ PubMed] [https://clinicaltrials.gov/study/NCT01343277 NCT01343277]
−
## '''Subgroup analysis:''' Hensley ML, Patel SR, von Mehren M, Ganjoo K, Jones RL, Staddon A, Rushing D, Milhem M, Monk B, Wang G, McCarthy S, Knoblauch RE, Parekh TV, Maki RG, Demetri GD. Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol. 2017 Sep;146(3):531-537. Epub 2017 Jun 24. [https://pubmed.ncbi.nlm.nih.gov/28651804 PubMed]
+
## '''Subgroup analysis:''' Hensley ML, Patel SR, von Mehren M, Ganjoo K, Jones RL, Staddon A, Rushing D, Milhem M, Monk B, Wang G, McCarthy S, Knoblauch RE, Parekh TV, Maki RG, Demetri GD. Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol. 2017 Sep;146(3):531-537. Epub 2017 Jun 24. [https://doi.org/10.1016/j.ygyno.2017.06.018 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5783302/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28651804/ PubMed]
−
## '''Update:''' Patel S, von Mehren M, Reed DR, Kaiser P, Charlson J, Ryan CW, Rushing D, Livingston M, Singh A, Seth R, Forscher C, D'Amato G, Chawla SP, McCarthy S, Wang G, Parekh T, Knoblauch R, Hensley ML, Maki RG, Demetri GD. Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. Cancer. 2019 Aug 1;125(15):2610-2620. Epub 2019 Jun 7. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.32117 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771856/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31173362 PubMed]
+
## '''Update:''' Patel S, von Mehren M, Reed DR, Kaiser P, Charlson J, Ryan CW, Rushing D, Livingston M, Singh A, Seth R, Forscher C, D'Amato G, Chawla SP, McCarthy S, Wang G, Parekh T, Knoblauch R, Hensley ML, Maki RG, Demetri GD. Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. Cancer. 2019 Aug 1;125(15):2610-2620. Epub 2019 Jun 7. [https://doi.org/10.1002/cncr.32117 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771856/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31173362/ PubMed]
−
# '''E7389-G000-309:''' Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/26874885 PubMed]
+
# '''E7389-G000-309:''' Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. [https://doi.org/10.1016/S0140-6736(15)01283-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26874885/ PubMed] [https://clinicaltrials.gov/study/NCT01327885 NCT01327885]
−
## '''Subgroup analysis:''' Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D'Adamo DR, Guo M, Chawla S. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017 Oct 20;35(30):3433-3439. Epub 2017 Aug 30. [https://doi.org/10.1200/JCO.2016.71.6605 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28854066 PubMed]
+
## '''Subgroup analysis:''' Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D'Adamo DR, Guo M, Chawla S. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017 Oct 20;35(30):3433-3439. Epub 2017 Aug 30. [https://doi.org/10.1200/JCO.2016.71.6605 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28854066/ PubMed]
−
 
 
 
==Eribulin monotherapy {{#subobject:427859|Regimen=1}}==
 
==Eribulin monotherapy {{#subobject:427859|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
===Regimen {{#subobject:2bcda0|Variant=1}}===
 
===Regimen {{#subobject:2bcda0|Variant=1}}===
 
{| class="wikitable" style="color:white; background-color:#404040"
 
{| class="wikitable" style="color:white; background-color:#404040"
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{| 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%"|Dates 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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016 (E7389-G000-309)]
+
|[https://doi.org/10.1016/S0140-6736(15)01283-0 Schöffski et al. 2016 (E7389-G000-309)]
 +
<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 +
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-202-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
 +
|-
 +
|} -->
 
|2011-2013
 
|2011-2013
−
| style="background-color:#1a9851" |Phase III (E-RT-switch-ic)
+
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
|[[#Dacarbazine_monotherapy|Dacarbazine]]
 
|[[#Dacarbazine_monotherapy|Dacarbazine]]
−
| style="background-color:#1a9850" |Superior OS (*)
+
| style="background-color:#1a9850" |Superior OS<sup>1</sup> (primary endpoint)<br>Median OS: 15.6 vs 8.4 mo<br>(HR 0.51, 95% CI 0.35-0.75)
 
|-
 
|-
 
|}
 
|}
−
''Note: Reported efficacy is based on the 2017 subgroup analysis.''
+
''<sup>1</sup>Reported efficacy is based on the 2017 subgroup analysis.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
*[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8
−
 
 
'''21-day cycles'''
 
'''21-day cycles'''
−
 
+
</div></div>
 
===References===
 
===References===
−
# '''E7389-G000-309:''' Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/26874885 PubMed]
+
# '''E7389-G000-309:''' Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. [https://doi.org/10.1016/S0140-6736(15)01283-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26874885/ PubMed] [https://clinicaltrials.gov/study/NCT01327885 NCT01327885]
−
## '''Subgroup analysis:''' Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D'Adamo DR, Guo M, Chawla S. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017 Oct 20;35(30):3433-3439. Epub 2017 Aug 30. [https://doi.org/10.1200/JCO.2016.71.6605 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28854066 PubMed]
+
## '''Subgroup analysis:''' Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D'Adamo DR, Guo M, Chawla S. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017 Oct 20;35(30):3433-3439. Epub 2017 Aug 30. [https://doi.org/10.1200/JCO.2016.71.6605 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28854066/ PubMed]
−
 
 
 
==Trabectedin monotherapy {{#subobject:cfc3ed|Regimen=1}}==
 
==Trabectedin monotherapy {{#subobject:cfc3ed|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
===Regimen {{#subobject:05c55d|Variant=1}}===
 
===Regimen {{#subobject:05c55d|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%"|Dates 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
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|[https://doi.org/10.1200/JCO.2008.21.0088 Demetri et al. 2009]
 
|[https://doi.org/10.1200/JCO.2008.21.0088 Demetri et al. 2009]
 
|2003-NR
 
|2003-NR
−
| style="background-color:#1a9851" |Randomized Phase II (E-switch-ic)
+
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
 
|[[#Trabectedin_monotherapy|Trabectedin]]; alternate schedule
 
|[[#Trabectedin_monotherapy|Trabectedin]]; alternate schedule
−
| style="background-color:#91cf60" |Seems to have superior TTP
+
| style="background-color:#91cf60" |Seems to have superior TTP (primary endpoint)<br>Median TTP: 3.7 vs 2.3 mo<br>(HR 0.73, 95% CI 0.55-0.97)
 
|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ Demetri et al. 2015 (ET743-SAR-3007)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ Demetri et al. 2015 (ET743-SAR-3007)]
−
|2011-2015
+
<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
−
| style="background-color:#1a9851" |Phase III (E-RT-switch-ic)
+
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-244-1 <span style="color:white;">ESMO-MCBS (2)</span>]'''
 +
|-
 +
|} -->
 +
|2011-2013
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
|[[#Dacarbazine_monotherapy|Dacarbazine]]
 
|[[#Dacarbazine_monotherapy|Dacarbazine]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
Line 157: Line 161:
 
|}
 
|}
 
''Note: in Demetri et al. 2015, this is listed as a "starting dose," but no adjustment instructions were provided in the manuscript.''
 
''Note: in Demetri et al. 2015, this is listed as a "starting dose," but no adjustment instructions were provided in the manuscript.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Trabectedin (Yondelis)]] 1.5 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
*[[Trabectedin (Yondelis)]] 1.5 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
−
 
+
====Supportive therapy====
−
====Supportive medications====
+
*[[Dexamethasone (Decadron)]] 20 mg IV once on day 1, prior to trabectedin
−
*[[Dexamethasone (Decadron)]] 20 mg IV once on day 1, prior to [[Trabectedin (Yondelis)]]
 
−
 
 
 
'''21-day cycles'''
 
'''21-day cycles'''
−
 
+
</div></div>
 
===References===
 
===References===
−
# Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, Lebedinsky C, Elsayed YA, Izquierdo MA, Gómez J, Park YC, Le Cesne A. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009 Sep 1;27(25):4188-96. Epub 2009 Aug 3. [https://doi.org/10.1200/JCO.2008.21.0088 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/19652065 PubMed]
+
# Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, Lebedinsky C, Elsayed YA, Izquierdo MA, Gómez J, Park YC, Le Cesne A. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009 Sep 1;27(25):4188-96. Epub 2009 Aug 3. [https://doi.org/10.1200/JCO.2008.21.0088 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19652065/ PubMed]
−
# '''ET743-SAR-3007:''' Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. [http://jco.ascopubs.org/content/34/8/786.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26371143 PubMed]
+
# '''ET743-SAR-3007:''' Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. [https://doi.org/10.1200/jco.2015.62.4734 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26371143/ PubMed] [https://clinicaltrials.gov/study/NCT01343277 NCT01343277]
−
## '''Subgroup analysis:''' Hensley ML, Patel SR, von Mehren M, Ganjoo K, Jones RL, Staddon A, Rushing D, Milhem M, Monk B, Wang G, McCarthy S, Knoblauch RE, Parekh TV, Maki RG, Demetri GD. Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol. 2017 Sep;146(3):531-537. Epub 2017 Jun 24. [https://pubmed.ncbi.nlm.nih.gov/28651804 PubMed]
+
## '''Subgroup analysis:''' Hensley ML, Patel SR, von Mehren M, Ganjoo K, Jones RL, Staddon A, Rushing D, Milhem M, Monk B, Wang G, McCarthy S, Knoblauch RE, Parekh TV, Maki RG, Demetri GD. Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol. 2017 Sep;146(3):531-537. Epub 2017 Jun 24. [https://doi.org/10.1016/j.ygyno.2017.06.018 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5783302/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28651804/ PubMed]
−
## '''Update:''' Patel S, von Mehren M, Reed DR, Kaiser P, Charlson J, Ryan CW, Rushing D, Livingston M, Singh A, Seth R, Forscher C, D'Amato G, Chawla SP, McCarthy S, Wang G, Parekh T, Knoblauch R, Hensley ML, Maki RG, Demetri GD. Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. Cancer. 2019 Aug 1;125(15):2610-2620. Epub 2019 Jun 7. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.32117 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771856/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31173362 PubMed]
+
## '''Update:''' Patel S, von Mehren M, Reed DR, Kaiser P, Charlson J, Ryan CW, Rushing D, Livingston M, Singh A, Seth R, Forscher C, D'Amato G, Chawla SP, McCarthy S, Wang G, Parekh T, Knoblauch R, Hensley ML, Maki RG, Demetri GD. Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. Cancer. 2019 Aug 1;125(15):2610-2620. Epub 2019 Jun 7. [https://doi.org/10.1002/cncr.32117 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771856/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31173362/ PubMed]
−
 
 
 
[[Category:Liposarcoma regimens]]
 
[[Category:Liposarcoma regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
 
[[Category:Soft tissue sarcomas]]
 
[[Category:Soft tissue sarcomas]]

Latest revision as of 02:18, 25 May 2024

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Section editor
Elizabethdavis2.jpg
 Elizabeth J. Davis, MD
Vanderbilt University
Nashville, TN, USA

Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!.
Note: these are regimens tested in subtype-specific populations, please see the main soft tissue sarcoma page for other regimens.

3 regimens on this page
5 variants on this page


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

NCCN

Advanced or metastatic disease, subsequent lines of therapy

Dacarbazine monotherapy

Regimen variant #1, 850 mg/m2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Schöffski et al. 2016 (E7389-G000-309) 2011-2013 Phase 3 (C) Eribulin Inferior OS1

1Reported efficacy is based on the 2017 subgroup analysis.

Chemotherapy

21-day cycles


Regimen variant #2, 1000 mg/m2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Demetri et al. 2015 (ET743-SAR-3007) 2011-2013 Phase 3 (C) Trabectedin Did not meet primary endpoint of OS
Schöffski et al. 2016 (E7389-G000-309) 2011-2013 Phase 3 (C) Eribulin Inferior OS1

1Reported efficacy is based on the 2017 subgroup analysis.
Note: this is listed as a "starting dose" in Demetri et al. 2015, but no adjustment instructions were provided in the manuscript.

Chemotherapy

21-day cycles


Regimen variant #3, 1200 mg/m2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Schöffski et al. 2016 (E7389-G000-309) 2011-2013 Phase 3 (C) Eribulin Inferior OS1

1Reported efficacy is based on the 2017 subgroup analysis.

Chemotherapy

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

References

  1. ET743-SAR-3007: Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01343277
    1. Subgroup analysis: Hensley ML, Patel SR, von Mehren M, Ganjoo K, Jones RL, Staddon A, Rushing D, Milhem M, Monk B, Wang G, McCarthy S, Knoblauch RE, Parekh TV, Maki RG, Demetri GD. Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol. 2017 Sep;146(3):531-537. Epub 2017 Jun 24. link to original article link to PMC article PubMed
    2. Update: Patel S, von Mehren M, Reed DR, Kaiser P, Charlson J, Ryan CW, Rushing D, Livingston M, Singh A, Seth R, Forscher C, D'Amato G, Chawla SP, McCarthy S, Wang G, Parekh T, Knoblauch R, Hensley ML, Maki RG, Demetri GD. Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. Cancer. 2019 Aug 1;125(15):2610-2620. Epub 2019 Jun 7. link to original article link to PMC article PubMed
  2. E7389-G000-309: Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. link to original article PubMed NCT01327885
    1. Subgroup analysis: Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D'Adamo DR, Guo M, Chawla S. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017 Oct 20;35(30):3433-3439. Epub 2017 Aug 30. link to original article contains dosing details in manuscript PubMed

Eribulin monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Comparator Comparative Efficacy
Schöffski et al. 2016 (E7389-G000-309) 2011-2013 Phase 3 (E-RT-switch-ic) Dacarbazine Superior OS1 (primary endpoint)
Median OS: 15.6 vs 8.4 mo
(HR 0.51, 95% CI 0.35-0.75)

1Reported efficacy is based on the 2017 subgroup analysis.

Chemotherapy

21-day cycles

References

  1. E7389-G000-309: Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. link to original article contains dosing details in abstract PubMed NCT01327885
    1. Subgroup analysis: Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D'Adamo DR, Guo M, Chawla S. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017 Oct 20;35(30):3433-3439. Epub 2017 Aug 30. link to original article contains dosing details in manuscript PubMed

Trabectedin monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Demetri et al. 2009 2003-NR Randomized Phase 2 (E-switch-ic) Trabectedin; alternate schedule Seems to have superior TTP (primary endpoint)
Median TTP: 3.7 vs 2.3 mo
(HR 0.73, 95% CI 0.55-0.97)
Demetri et al. 2015 (ET743-SAR-3007) 2011-2013 Phase 3 (E-RT-switch-ic) Dacarbazine Did not meet primary endpoint of OS

Note: in Demetri et al. 2015, this is listed as a "starting dose," but no adjustment instructions were provided in the manuscript.

Chemotherapy

Supportive therapy

21-day cycles

References

  1. Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, Lebedinsky C, Elsayed YA, Izquierdo MA, Gómez J, Park YC, Le Cesne A. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009 Sep 1;27(25):4188-96. Epub 2009 Aug 3. link to original article contains dosing details in abstract PubMed
  2. ET743-SAR-3007: Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01343277
    1. Subgroup analysis: Hensley ML, Patel SR, von Mehren M, Ganjoo K, Jones RL, Staddon A, Rushing D, Milhem M, Monk B, Wang G, McCarthy S, Knoblauch RE, Parekh TV, Maki RG, Demetri GD. Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol. 2017 Sep;146(3):531-537. Epub 2017 Jun 24. link to original article link to PMC article PubMed
    2. Update: Patel S, von Mehren M, Reed DR, Kaiser P, Charlson J, Ryan CW, Rushing D, Livingston M, Singh A, Seth R, Forscher C, D'Amato G, Chawla SP, McCarthy S, Wang G, Parekh T, Knoblauch R, Hensley ML, Maki RG, Demetri GD. Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. Cancer. 2019 Aug 1;125(15):2610-2620. Epub 2019 Jun 7. link to original article link to PMC article PubMed
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