Difference between revisions of "Ewing sarcoma, pediatric - historical"

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m (Text replacement - "As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. " to "")
 
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[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Ewing sarcoma, pediatric|main pediatric Ewing sarcoma page]] for current regimens.
+
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the [[Ewing sarcoma, pediatric|main pediatric Ewing sarcoma page]] for current regimens.
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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: #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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<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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{{TOC limit|limit=4}}
 
{{TOC limit|limit=4}}
−
 
 
=Upfront therapy, localized disease=
 
=Upfront therapy, localized disease=
−
==COG AEWS0031 Induction A==
+
==COG AEWS0031 Protocol A==
−
===Regimen===
+
<div class="toccolours" style="background-color:#c8a2c8">
−
*Regimen A is a standard regimen consisting of 21 day cycles
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
====Chemotherapy, VDC portion====
+
!style="width: 20%"|Study
−
*[[Vincristine (Oncovin)]] as follows:
+
!style="width: 20%"|Dates of enrollment
−
**Cycles 1 & 3: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
+
!style="width: 20%"|Comparator
−
*[[Doxorubicin (Adriamycin)]] as follows:
+
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
**Cycles 1 & 3: 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1
+
|-
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494838/ Womer et al. 2012 (COG AEWS0031)]
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
+
|2001-05 to 2005-08
−
**Cycles 1 & 3: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
+
| style="background-color:#1a9851" |Phase 3 (C)
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
|[[#COG_AEWS0031_Protocol_B|Intensified treatment]]
−
====Supportive medications, VDC portion====
+
| style="background-color:#fc8d59" |Seems to have inferior EFS
−
*[[Mesna (Mesnex)]] as follows:
+
|-
−
**Cycles 1 & 3: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
+
|}
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup>
+
''Protocol A is a standard protocol consisting of 14 21-day cycles''
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
+
<div class="toccolours" style="background-color:#ee6b6e">
−
*[[Filgrastim (Neupogen)]] as follows:
+
===Induction===
−
**Cycles 1 & 3: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
+
<div class="toccolours" style="background-color:#b3e2cd">
−
***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+
====Chemotherapy, VDC portion (cycles 1 & 3)====
−
'''21 day cycle'''
+
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
−
====Chemotherapy, IE portion====
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
−
*[[Ifosfamide (Ifex)]] as follows:
+
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV continuous infusion over 48 hours, started on day 1
−
**Cycles 2 & 4: 1800 mg/m<sup>2</sup> IV infusion over 1 hour once on day 1 to 5
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
*[[Etoposide (Vepesid)]] as follows:
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
**Cycles 2 & 4: 100 mg/m<sup>2</sup> IV infusion over 1 to 2 hours once on days 1 to 5
+
====Supportive therapy, VDC portion (cycles 1 & 3)====
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
−
====Supportive medications, IE portion====
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
−
*[[Mesna (Mesnex)]] as follows:
+
**Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
−
**Cycles 2 & 4: 1080 mg/m<sup>2</sup> IV continuous infusion on day 1
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Ifosfamide (Ifex)]] m<sup>2</sup>
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Ifosfamide (Ifex)]] and remain until at least 8 hours after the end of the [[Ifosfamide (Ifex)]] infusion
+
====Chemotherapy, IE portion (cycles 2 & 4)====
−
*[[Filgrastim (Neupogen)]] as follows:
+
*[[Ifosfamide (Ifex)]] 1800 mg/m<sup>2</sup> IV infusion over 1 hour once per day on days 1 to 5
−
**Cycles 2 & 4: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV infusion over 1 to 2 hours once per day on days 1 to 5
−
'''21 day cycle'''
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
 
+
====Supportive therapy, IE portion (cycles 2 & 4)====
−
====References====
+
*[[Mesna (Mesnex)]] 1080 mg/m<sup>2</sup> IV continuous infusion on day 1
−
#'''COG AEWS0031:''' Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, and Weiss AR. Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2012 Nov 20;30(33):4148-4154. [https://dx.doi.org/10.1200%2FJCO.2011.41.5703 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494838/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23091096/ PubMed] NCT00006734
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m<sup>2</sup>
−
 
+
**Ccontinuous infusion should be started at the same time as the ifosfamide and remain until at least 8 hours after the end of the ifosfamide infusion
−
==COG AEWS0031 Continuation A==
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 6
 +
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
 +
'''21-day cycle for 4 cycles, followed by:'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#ee6b6e">
 +
===Continuation===
 
*At week 13 patients either underwent surgery, received radiation, or both
 
*At week 13 patients either underwent surgery, received radiation, or both
 
*Radiation coincided with cycle 5
 
*Radiation coincided with cycle 5
−
===Regimen===
+
''Note: the cycle count for this phase starts at cycle 5.''
−
====Chemotherapy, VDC portion====
+
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy, VDC portion (cycles 5 & 9)====
 
  Cycle 5 begins on week 15 in patients receiving surgery and on week 13 in Regimen A<sub>2</sub>
 
  Cycle 5 begins on week 15 in patients receiving surgery and on week 13 in Regimen A<sub>2</sub>
−
*[[Vincristine (Oncovin)]] as follows:
+
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
−
**Cycle 5 & 9: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
+
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV continuous infusion over 48 hours, started on day 1
−
*[[Doxorubicin (Adriamycin)]] as follows:
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
**Cycle 5 & 9: 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
+
====Supportive medication, VDC portion (cycles 5 & 9)====
−
**Cycle 5 & 9: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
+
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
−
====Supportive medication, VDC portion====
+
**Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
−
*[[Mesna (Mesnex)]] as follows:
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
−
**Cycle 5 & 9: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup>
+
====Chemotherapy, IE portion (cycles 6, 8, 10, 12, 14)====
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
+
*[[Ifosfamide (Ifex)]] 1800 mg/m<sup>2</sup> IV infusion over 1 hour once per day on days 1 to 5
−
*[[Filgrastim (Neupogen)]] as follows:
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
**Cycle 5 & 9: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV infusion over 1 to 2 hours once per day on days 1 to 5
−
***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
'''21 day cycle'''
+
====Supportive therapy, IE portion (cycles 6, 8, 10, 12, 14)====
−
====Chemotherapy, IE portion====
+
*[[Mesna (Mesnex)]] 1080 mg/m<sup>2</sup> IV continuous infusion on day 1
−
*[[Ifosfamide (Ifex)]] as follows:
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m<sup>2</sup>
−
**Cycle 6, 8, 10, 12, & 14: 1800 mg/m<sup>2</sup> IV infusion over 1 hour once on day 1 to 5
+
**Continuous infusion should be started at the same time as the ifosfamide and remain until at least 8 hours after the end of the ifosfamide infusion
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 6
−
*[[Etoposide (Vepesid)]] as follows:
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
**Cycle 6, 8, 10, 12, & 14: 100 mg/m<sup>2</sup> IV infusion over 1 to 2 hours once on days 1 to 5
+
====Chemotherapy, VDC portion Regimen A<sub>1</sub> (cycle 7; Surgery Only)====
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
−
====Supportive medications, IE portion====
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
−
*[[Mesna (Mesnex)]] as follows:
+
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV continuous infusion over 48 hours, started on day 1
−
**Cycle 6, 8, 10, 12, & 14: 1080 mg/m<sup>2</sup> IV continuous infusion on day 1
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Ifosfamide (Ifex)]] m<sup>2</sup>
+
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Ifosfamide (Ifex)]] and remain until at least 8 hours after the end of the [[Ifosfamide (Ifex)]] infusion
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
*[[Filgrastim (Neupogen)]] as follows:
+
====Supportive therapy, VDC portion Regimen A<sub>1</sub> (cycle 7; Surgery Only)====
−
**Cycle 6, 8, 10, 12, & 14: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6
+
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
−
***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
−
'''21 day cycle'''
+
**Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
−
====Chemotherapy, VDC portion Regimen A<sub>1</sub> (Surgery Only)====
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
−
*[[Vincristine (Oncovin)]] as follows:
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
**Cycle 7: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
+
====Chemotherapy, VC portion Regimen A<sub>2</sub> & A<sub>3</sub> (cycle 7; Radiation w/ or w/o Surgery)====
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
+
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
−
*[[Doxorubicin (Adriamycin)]] as follows:
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
−
**Cycle 7: 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
+
====Supportive therapy, VC portion Regimen A<sub>2</sub> & A<sub>3</sub> (cycle 7; Radiation w/ or w/o Surgery)====
−
**Cycle 7: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
+
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
−
====Supportive therapy, VDC portion Regimen A<sub>1</sub> (Surgery Only)====
+
**Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
−
*[[Mesna (Mesnex)]] as follows:
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
−
**Cycle 7: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup>
+
====Chemotherapy, VC portion Regimen A<sub>1</sub> (cycle 11; Surgery Only)====
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
+
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
−
*[[Filgrastim (Neupogen)]] as follows:
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
−
**Cycle 7: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
+
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
'''21 day cycle'''
+
====Supportive therapy, VC portion Regimen A<sub>1</sub> (cycle 11; Surgery Only)====
−
====Chemotherapy, VC portion Regimen A<sub>2</sub> & A<sub>3</sub> (Radiation w/ or w/o Surgery)====
+
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
−
*[[Vincristine (Oncovin)]] as follows:
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
−
**Cycle 7: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
+
**Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
**Cycle 7: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
+
====Chemotherapy, VDC portion Regimen A<sub>2</sub> & A<sub>3</sub> (cycle 11; Radiation w/ or w/o Surgery)====
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
−
====Supportive medications, VC portion Regimen A<sub>2</sub> & A<sub>3</sub> (Radiation w/ or w/o Surgery)====
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
−
*[[Mesna (Mesnex)]] as follows:
+
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV continuous infusion over 48 hours, started on day 1
−
**Cycle 7: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup>
+
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
*[[Filgrastim (Neupogen)]] as follows:
+
====Supportive therapy, VDC portion Regimen A<sub>2</sub> & A<sub>3</sub> (cycle 11; Radiation w/ or w/o Surgery)====
−
**Cycle 7: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
+
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
−
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
−
'''21 day cycle'''
+
**Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
−
====Chemotherapy, VC portion Regimen A<sub>1</sub> (Surgery Only)====
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
−
*[[Vincristine (Oncovin)]] as follows:
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
**Cycle 11: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
+
====Chemotherapy, VC portion (cycle 13)====
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
+
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
−
**Cycle 11: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
+
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
====Supportive medications, VC portion Regimen A<sub>1</sub> (Surgery Only)====
+
====Supportive therapy, VC portion (cycle 13)====
−
*[[Mesna (Mesnex)]] as follows:
+
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
−
**Cycle 11: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup>
+
**Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
−
*[[Filgrastim (Neupogen)]] as follows:
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
**Cycle 11: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
+
'''21-day cycle for 9 cycles (13 cycles total)'''
−
***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+
</div></div></div>
−
'''21 day cycle'''
+
===References===
−
====Chemotherapy, VDC portion Regimen A<sub>2</sub> & A<sub>3</sub> (Radiation w/ or w/o Surgery)====
+
#'''COG AEWS0031:''' Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, and Weiss AR. Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2012 Nov 20;30(33):4148-4154. Epub 2012 Oct 22. [https://doi.org/10.1200/jco.2011.41.5703 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494838/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23091096/ PubMed] [https://clinicaltrials.gov/study/NCT00006734 NCT00006734]
−
*[[Vincristine (Oncovin)]] as follows:
+
##'''Update:''' Cash T, Krailo MD, Buxton AB, Pawel BR, Healey JH, Binitie O, Marcus KJ, Grier HE, Grohar PJ, Reed DR, Weiss AR, Gorlick R, Janeway KA, DuBois SG, Womer RB. Long-Term Outcomes in Patients With Localized Ewing Sarcoma Treated With Interval-Compressed Chemotherapy on Children's Oncology Group Study AEWS0031. J Clin Oncol. 2023 Oct 20;41(30):4724-4728. Epub 2023 Aug 31. [https://doi.org/10.1200/jco.23.00053 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37651654/ PubMed]
−
**Cycle 11: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
 
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycle 11: 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1
 
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycle 11: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
 
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
 
−
====Supportive medications, VDC portion Regimen A<sub>2</sub> & A<sub>3</sub> (Radiation w/ or w/o Surgery)====
 
−
*[[Mesna (Mesnex)]] as follows:
 
−
**Cycle 11: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
 
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup>
 
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
 
−
*[[Filgrastim (Neupogen)]] as follows:
 
−
**Cycle 11: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
 
−
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
 
−
'''21 day cycle'''
 
−
====Chemotherapy, VC portion====
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycle 13: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
 
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycle 13: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
 
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
 
−
====Supportive medications, VC portion====
 
−
*[[Mesna (Mesnex)]] as follows:
 
−
**Cycle 13: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
 
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup>
 
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
 
−
*[[Filgrastim (Neupogen)]] as follows:
 
−
**Cycle 13: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
 
−
***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
 
−
'''21 day cycle'''
 
  
−
====References====
+
==COG AEWS0031 Protocol B==
−
#'''COG AEWS0031:''' Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, and Weiss AR. Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2012 Nov 20;30(33):4148-4154. [https://dx.doi.org/10.1200%2FJCO.2011.41.5703 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494838/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23091096/ PubMed] NCT00006734
+
<div class="toccolours" style="background-color:#c8a2c8">
−
 
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
==COG AEWS0031 Induction B==
+
!style="width: 20%"|Study
−
*Regimen B is a consolidated regimen consisting of 14 day cycles
+
!style="width: 20%"|Dates of enrollment
−
===Regimen===
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
 
+
!style="width: 20%"|Comparator
−
====Chemotherapy, VDC portion====
+
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
*[[Vincristine (Oncovin)]] as follows:
+
|-
−
**Cycles 1, 3, & 5: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494838/ Womer et al. 2012 (COG AEWS0031)]
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
+
|2001-05 to 2005-08
−
*[[Doxorubicin (Adriamycin)]] as follows:
+
| style="background-color:#1a9851" |Phase 3 (E-esc)
−
**Cycles 1, 3, & 5: 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1
+
|[[#COG_AEWS0031_Protocol_A|Standard treatment]]
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
| style="background-color:#91cf60" |Seems to have superior EFS (primary endpoint)<br>EFS60: 73% vs 65%<br>(HR 0.74, 95% CI 0.54-0.99)<br><br>Seems to have superior OS (secondary endpoint)<br>OS60: 83% vs 77%<br>(HR 0.69, 95% CI 0.47-1.00)
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
+
|-
−
**Cycles 1, 3, & 5: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
+
|}
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
''Note: Protocol B is a consolidated regimen consisting of 14-day cycles.''
−
====Supportive medications, VDC portion====
+
<div class="toccolours" style="background-color:#ee6b6e">
−
*[[Mesna (Mesnex)]] as follows:
+
===Induction===
−
**Cycles 1, 3, & 5: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
+
<div class="toccolours" style="background-color:#b3e2cd">
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup>
+
====Chemotherapy, VDC portion (cycles 1, 3, 5)====
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
+
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
−
*[[Filgrastim (Neupogen)]] as follows:
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
−
**Cycles 1, 3, & 5: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
+
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV continuous infusion over 48 hours, started on day 1
−
***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
'''14 day cycle'''
+
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
====Chemotherapy, IE portion====
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
*[[Ifosfamide (Ifex)]] as follows:
+
====Supportive therapy, VDC portion (cycles 1, 3, 5)====
−
**Cycle 2, 4, & 6: 1800 mg/m<sup>2</sup> IV infusion over 1 hour once on day 1 to 5
+
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
−
*[[Etoposide (Vepesid)]] as follows:
+
**Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
−
**Cycle 2, 4, & 6: 100 mg/m<sup>2</sup> IV infusion over 1 to 2 hours once on days 1 to 5
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
====Supportive medications, IE portion====
+
====Chemotherapy, IE portion (cycles 2, 4, 6)====
−
*[[Mesna (Mesnex)]] as follows:
+
*[[Ifosfamide (Ifex)]] 1800 mg/m<sup>2</sup> IV infusion over 1 hour once per day on days 1 to 5
−
**Cycle 2, 4, & 6: 1080 mg/m<sup>2</sup> IV continuous infusion on day 1
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Ifosfamide (Ifex)]] m<sup>2</sup>
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV infusion over 1 to 2 hours once per day on days 1 to 5
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Ifosfamide (Ifex)]] and remain until at least 8 hours after the end of the [[Ifosfamide (Ifex)]] infusion
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
*[[Filgrastim (Neupogen)]] as follows:
+
====Supportive therapy, IE portion (cycles 2, 4, 6)====
−
**Cycle 2, 4, & 6: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6
+
*[[Mesna (Mesnex)]] 1080 mg/m<sup>2</sup> IV continuous infusion on day 1
−
***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m<sup>2</sup>
−
'''14 day cycle'''
+
**Continuous infusion should be started at the same time as the ifosfamide and remain until at least 8 hours after the end of the ifosfamide infusion
−
 
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 6
−
====References====
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
#'''COG AEWS0031:''' Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, and Weiss AR. Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2012 Nov 20;30(33):4148-4154. [https://dx.doi.org/10.1200%2FJCO.2011.41.5703 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494838/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23091096/ PubMed] NCT00006734
+
'''14-day cycle for 6 cycles, followed by:'''
−
 
+
</div></div><br>
−
==COG AEWS0031 Continuation B==
+
<div class="toccolours" style="background-color:#ee6b6e">
 +
===Continuation===
 
*At week 13 patients either underwent surgery, received radiation, or both
 
*At week 13 patients either underwent surgery, received radiation, or both
 
*Radiation coincided with cycle 7
 
*Radiation coincided with cycle 7
−
===Regimen===
+
''Note: The counting starts at cycle 7, which begins on week 15 in patients receiving surgery and on week 13 in Regimen B<sub>2</sub>.''
−
 
+
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy, VDC portion====
+
====Chemotherapy, VDC portion (cycle 7)====
−
Cycle 7 begins on week 15 in patients receiving surgery and on week 13 in Regimen B<sub>2</sub>
+
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
−
*[[Vincristine (Oncovin)]] as follows:
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
−
**Cycle 7: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
+
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV continuous infusion over 48 hours, started on day 1
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
*[[Doxorubicin (Adriamycin)]] as follows:
+
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
**Cycle 7: 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
====Supportive therapy, VDC portion (cycle 7)====
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
+
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
−
**Cycle 7: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
**Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
−
====Supportive medications, VDC portion====
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
−
*[[Mesna (Mesnex)]] as follows:
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
**Cycle 7: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
+
====Chemotherapy, IE portion (cycles 8, 10, 12, 14)====
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup>
+
*[[Ifosfamide (Ifex)]] 1800 mg/m<sup>2</sup> IV infusion over 1 hour once per day on days 1 to 5
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
*[[Filgrastim (Neupogen)]] as follows:
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV infusion over 1 to 2 hours once per day on days 1 to 5
−
**Cycle 7: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+
====Supportive therapy, IE portion (cycles 8, 10, 12, 14)====
−
'''14 day cycle'''
+
*[[Mesna (Mesnex)]] 1080 mg/m<sup>2</sup> IV continuous infusion on day 1
−
 
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m<sup>2</sup>
−
 
+
**Continuous infusion should be started at the same time as the ifosfamide and remain until at least 8 hours after the end of the ifosfamide infusion
−
====Chemotherapy, IE portion====
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 6
−
*[[Ifosfamide (Ifex)]] as follows:
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
**Cycle 8, 10, 12, & 14: 1800 mg/m<sup>2</sup> IV infusion over 1 hour once on day 1 to 5
+
====Chemotherapy, VDC portion Regimen B<sub>1</sub> (cycle 9; Surgery Only)====
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
−
*[[Etoposide (Vepesid)]] as follows:
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
−
**Cycle 8, 10, 12, & 14: 100 mg/m<sup>2</sup> IV infusion over 1 to 2 hours once on days 1 to 5
+
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV continuous infusion over 48 hours, started on day 1
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
====Supportive medications, IE portion====
+
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
*[[Mesna (Mesnex)]] as follows:
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
**Cycle 8, 10, 12, & 14: 1080 mg/m<sup>2</sup> IV continuous infusion on day 1
+
====Supportive therapy, VDC portion Regimen B<sub>1</sub> (cycle 9; Surgery Only)====
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Ifosfamide (Ifex)]] m<sup>2</sup>
+
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Ifosfamide (Ifex)]] and remain until at least 8 hours after the end of the [[Ifosfamide (Ifex)]] infusion
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
−
*[[Filgrastim (Neupogen)]] as follows:
+
**Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
−
**Cycle 8, 10, 12, & 14: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
−
***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
'''14 day cycle'''
+
====Chemotherapy, VC portion Regimen B<sub>2</sub> & B<sub>3</sub> (cycle 9; Radiation w/ or w/o Surgery)====
−
 
+
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
−
====Chemotherapy, VDC portion Regimen B<sub>1</sub> (Surgery Only)====
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
−
*[[Vincristine (Oncovin)]] as follows:
+
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
**Cycle 9: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
+
====Supportive therapy, VC portion Regimen B<sub>2</sub> & B<sub>3</sub> (cycle 9; Radiation w/ or w/o Surgery)====
−
*[[Doxorubicin (Adriamycin)]] as follows:
+
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
−
**Cycle 9: 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
**Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
−
**Cycle 9: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
====Chemotherapy, VC portion (cycle 11)====
−
====Supportive medications, VDC portion Regimen B<sub>1</sub> (Surgery Only)====
+
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
−
*[[Mesna (Mesnex)]] as follows:
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
−
**Cycle 9: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup>
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
+
====Supportive therapy, VC portion (cycle 11)====
−
*[[Filgrastim (Neupogen)]] as follows:
+
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
−
**Cycle 9: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
−
***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+
**Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
−
'''14 day cycle'''
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
−
====Chemotherapy, VC portion Regimen B<sub>2</sub> & B<sub>3</sub> (Radiation w/ or w/o Surgery)====
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
*[[Vincristine (Oncovin)]] as follows:
+
====Chemotherapy, VC portion Regimen B<sub>1</sub> (cycle 13; Surgery Only)====
−
**Cycle 9: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
+
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycle 9: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
 
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
 
−
====Supportive medications, VC portion Regimen B<sub>2</sub> & B<sub>3</sub> (Radiation w/ or w/o Surgery)====
 
−
*[[Mesna (Mesnex)]] as follows:
 
−
**Cycle 9: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
 
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup>
 
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
 
−
*[[Filgrastim (Neupogen)]] as follows:
 
−
**Cycle 9: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
 
−
***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
 
−
'''14 day cycle'''
 
−
====Chemotherapy, VC portion====
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycle 11: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
 
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycle 11: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
 
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
 
−
====Supportive medications, VC portion====
 
−
*[[Mesna (Mesnex)]] as follows:
 
−
**Cycle 11: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
 
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup>
 
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
 
−
*[[Filgrastim (Neupogen)]] as follows:
 
−
**Cycle 11: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
 
−
***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
 
−
'''14 day cycle'''
 
−
====Chemotherapy, VC portion Regimen B<sub>1</sub> (Surgery Only)====
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycle 13: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
 
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycle 13: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
 
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
 
−
====Supportive medications, VC portion Regimen B<sub>1</sub> (Surgery Only)====
 
−
*[[Mesna (Mesnex)]] as follows:
 
−
**Cycle 13: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
 
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup>
 
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
 
−
*[[Filgrastim (Neupogen)]] as follows:
 
−
**Cycle 13: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
 
−
***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
 
−
'''14 day cycle'''
 
−
====Chemotherapy, VDC portion Regimen B<sub>2</sub> & B<sub>3</sub> (Radiation w/ or w/o Surgery)====
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycle 13: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
 
 
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
 
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated  
−
*[[Doxorubicin (Adriamycin)]] as follows:
+
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
**Cycle 13: 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
====Supportive therapy, VC portion Regimen B<sub>1</sub> (cycle 13; Surgery Only)====
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
+
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
−
**Cycle 13: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
−
***Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
+
**Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
−
====Supportive medications, VDC portion Regimen B<sub>2</sub> & B<sub>3</sub> (Radiation w/ or w/o Surgery)====
+
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
−
*[[Mesna (Mesnex)]] as follows:
+
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
−
**Cycle 13: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
+
====Chemotherapy, VDC portion Regimen B<sub>2</sub> & B<sub>3</sub> (cycle 13; Radiation w/ or w/o Surgery)====
−
***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup>
+
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
−
***[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
*[[Filgrastim (Neupogen)]] as follows:
+
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV continuous infusion over 48 hours, started on day 1
−
**Cycle 13: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
'''14 day cycle'''
+
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
−
====References====
+
====Supportive therapy, VDC portion Regimen B<sub>2</sub> & B<sub>3</sub> (cycle 13; Radiation w/ or w/o Surgery)====
−
#'''COG AEWS0031:''' Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, and Weiss AR. Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2012 Nov 20;30(33):4148-4154. [https://dx.doi.org/10.1200%2FJCO.2011.41.5703 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494838/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23091096/ PubMed] NCT00006734
+
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
−
 
+
**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
 +
**Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
 +
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
 +
**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
 +
'''14-day cycle for 8 cycles (14 cycles total)'''
 +
</div></div></div>
 +
===References===
 +
#'''COG AEWS0031:''' Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, and Weiss AR. Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2012 Nov 20;30(33):4148-4154. Epub 2012 Oct 22. [https://doi.org/10.1200/jco.2011.41.5703 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494838/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23091096/ PubMed] [https://clinicaltrials.gov/study/NCT00006734 NCT00006734]
 +
##'''Update:''' Cash T, Krailo MD, Buxton AB, Pawel BR, Healey JH, Binitie O, Marcus KJ, Grier HE, Grohar PJ, Reed DR, Weiss AR, Gorlick R, Janeway KA, DuBois SG, Womer RB. Long-Term Outcomes in Patients With Localized Ewing Sarcoma Treated With Interval-Compressed Chemotherapy on Children's Oncology Group Study AEWS0031. J Clin Oncol. 2023 Oct 20;41(30):4724-4728. Epub 2023 Aug 31. [https://doi.org/10.1200/jco.23.00053 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37651654/ PubMed]
 
[[Category:Ewing sarcoma regimens]]
 
[[Category:Ewing sarcoma regimens]]
 
[[Category:Historical regimens]]
 
[[Category:Historical regimens]]

Latest revision as of 11:21, 13 May 2024

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main pediatric Ewing sarcoma page for current regimens.

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Upfront therapy, localized disease

COG AEWS0031 Protocol A

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Womer et al. 2012 (COG AEWS0031) 2001-05 to 2005-08 Phase 3 (C) Intensified treatment Seems to have inferior EFS

Protocol A is a standard protocol consisting of 14 21-day cycles

Induction

Chemotherapy, VDC portion (cycles 1 & 3)

  • Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV push once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Doxorubicin (Adriamycin) 75 mg/m2 IV continuous infusion over 48 hours, started on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Cyclophosphamide (Cytoxan) 1200 mg/m2 IV over 60 minutes once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, VDC portion (cycles 1 & 3)

  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m2
    • Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

Chemotherapy, IE portion (cycles 2 & 4)

  • Ifosfamide (Ifex) 1800 mg/m2 IV infusion over 1 hour once per day on days 1 to 5
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Etoposide (Vepesid) 100 mg/m2 IV infusion over 1 to 2 hours once per day on days 1 to 5
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, IE portion (cycles 2 & 4)

  • Mesna (Mesnex) 1080 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m2
    • Ccontinuous infusion should be started at the same time as the ifosfamide and remain until at least 8 hours after the end of the ifosfamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 6
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

21-day cycle for 4 cycles, followed by:


Continuation

  • At week 13 patients either underwent surgery, received radiation, or both
  • Radiation coincided with cycle 5

Note: the cycle count for this phase starts at cycle 5.

Chemotherapy, VDC portion (cycles 5 & 9)

Cycle 5 begins on week 15 in patients receiving surgery and on week 13 in Regimen A2
  • Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV push once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Doxorubicin (Adriamycin) 75 mg/m2 IV continuous infusion over 48 hours, started on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Cyclophosphamide (Cytoxan) 1200 mg/m2 IV over 60 minutes once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive medication, VDC portion (cycles 5 & 9)

  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m2
    • Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

Chemotherapy, IE portion (cycles 6, 8, 10, 12, 14)

  • Ifosfamide (Ifex) 1800 mg/m2 IV infusion over 1 hour once per day on days 1 to 5
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Etoposide (Vepesid) 100 mg/m2 IV infusion over 1 to 2 hours once per day on days 1 to 5
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, IE portion (cycles 6, 8, 10, 12, 14)

  • Mesna (Mesnex) 1080 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m2
    • Continuous infusion should be started at the same time as the ifosfamide and remain until at least 8 hours after the end of the ifosfamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 6
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

Chemotherapy, VDC portion Regimen A1 (cycle 7; Surgery Only)

  • Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV push once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Doxorubicin (Adriamycin) 75 mg/m2 IV continuous infusion over 48 hours, started on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Cyclophosphamide (Cytoxan) 1200 mg/m2 IV over 60 minutes once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, VDC portion Regimen A1 (cycle 7; Surgery Only)

  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m2
    • Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

Chemotherapy, VC portion Regimen A2 & A3 (cycle 7; Radiation w/ or w/o Surgery)

  • Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV push once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Cyclophosphamide (Cytoxan) 1200 mg/m2 IV over 60 minutes once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, VC portion Regimen A2 & A3 (cycle 7; Radiation w/ or w/o Surgery)

  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m2
    • Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

Chemotherapy, VC portion Regimen A1 (cycle 11; Surgery Only)

  • Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV push once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Cyclophosphamide (Cytoxan) 1200 mg/m2 IV over 60 minutes once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, VC portion Regimen A1 (cycle 11; Surgery Only)

  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m2
    • Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

Chemotherapy, VDC portion Regimen A2 & A3 (cycle 11; Radiation w/ or w/o Surgery)

  • Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV push once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Doxorubicin (Adriamycin) 75 mg/m2 IV continuous infusion over 48 hours, started on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Cyclophosphamide (Cytoxan) 1200 mg/m2 IV over 60 minutes once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, VDC portion Regimen A2 & A3 (cycle 11; Radiation w/ or w/o Surgery)

  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m2
    • Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

Chemotherapy, VC portion (cycle 13)

  • Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV push once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Cyclophosphamide (Cytoxan) 1200 mg/m2 IV over 60 minutes once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, VC portion (cycle 13)

  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m2
    • Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

21-day cycle for 9 cycles (13 cycles total)

References

  1. COG AEWS0031: Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, and Weiss AR. Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2012 Nov 20;30(33):4148-4154. Epub 2012 Oct 22. link to original article link to PMC article PubMed NCT00006734
    1. Update: Cash T, Krailo MD, Buxton AB, Pawel BR, Healey JH, Binitie O, Marcus KJ, Grier HE, Grohar PJ, Reed DR, Weiss AR, Gorlick R, Janeway KA, DuBois SG, Womer RB. Long-Term Outcomes in Patients With Localized Ewing Sarcoma Treated With Interval-Compressed Chemotherapy on Children's Oncology Group Study AEWS0031. J Clin Oncol. 2023 Oct 20;41(30):4724-4728. Epub 2023 Aug 31. link to original article PubMed

COG AEWS0031 Protocol B

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Womer et al. 2012 (COG AEWS0031) 2001-05 to 2005-08 Phase 3 (E-esc) Standard treatment Seems to have superior EFS (primary endpoint)
EFS60: 73% vs 65%
(HR 0.74, 95% CI 0.54-0.99)

Seems to have superior OS (secondary endpoint)
OS60: 83% vs 77%
(HR 0.69, 95% CI 0.47-1.00)

Note: Protocol B is a consolidated regimen consisting of 14-day cycles.

Induction

Chemotherapy, VDC portion (cycles 1, 3, 5)

  • Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV push once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Doxorubicin (Adriamycin) 75 mg/m2 IV continuous infusion over 48 hours, started on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Cyclophosphamide (Cytoxan) 1200 mg/m2 IV over 60 minutes once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, VDC portion (cycles 1, 3, 5)

  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m2
    • Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

Chemotherapy, IE portion (cycles 2, 4, 6)

  • Ifosfamide (Ifex) 1800 mg/m2 IV infusion over 1 hour once per day on days 1 to 5
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Etoposide (Vepesid) 100 mg/m2 IV infusion over 1 to 2 hours once per day on days 1 to 5
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, IE portion (cycles 2, 4, 6)

  • Mesna (Mesnex) 1080 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m2
    • Continuous infusion should be started at the same time as the ifosfamide and remain until at least 8 hours after the end of the ifosfamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 6
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

14-day cycle for 6 cycles, followed by:


Continuation

  • At week 13 patients either underwent surgery, received radiation, or both
  • Radiation coincided with cycle 7

Note: The counting starts at cycle 7, which begins on week 15 in patients receiving surgery and on week 13 in Regimen B2.

Chemotherapy, VDC portion (cycle 7)

  • Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV push once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Doxorubicin (Adriamycin) 75 mg/m2 IV continuous infusion over 48 hours, started on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Cyclophosphamide (Cytoxan) 1200 mg/m2 IV over 60 minutes once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, VDC portion (cycle 7)

  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m2
    • Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

Chemotherapy, IE portion (cycles 8, 10, 12, 14)

  • Ifosfamide (Ifex) 1800 mg/m2 IV infusion over 1 hour once per day on days 1 to 5
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Etoposide (Vepesid) 100 mg/m2 IV infusion over 1 to 2 hours once per day on days 1 to 5
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, IE portion (cycles 8, 10, 12, 14)

  • Mesna (Mesnex) 1080 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m2
    • Continuous infusion should be started at the same time as the ifosfamide and remain until at least 8 hours after the end of the ifosfamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 6
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

Chemotherapy, VDC portion Regimen B1 (cycle 9; Surgery Only)

  • Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV push once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Doxorubicin (Adriamycin) 75 mg/m2 IV continuous infusion over 48 hours, started on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Cyclophosphamide (Cytoxan) 1200 mg/m2 IV over 60 minutes once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, VDC portion Regimen B1 (cycle 9; Surgery Only)

  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m2
    • Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

Chemotherapy, VC portion Regimen B2 & B3 (cycle 9; Radiation w/ or w/o Surgery)

  • Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV push once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Cyclophosphamide (Cytoxan) 1200 mg/m2 IV over 60 minutes once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, VC portion Regimen B2 & B3 (cycle 9; Radiation w/ or w/o Surgery)

  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m2
    • Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

Chemotherapy, VC portion (cycle 11)

  • Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV push once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Cyclophosphamide (Cytoxan) 1200 mg/m2 IV over 60 minutes once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, VC portion (cycle 11)

  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m2
    • Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

Chemotherapy, VC portion Regimen B1 (cycle 13; Surgery Only)

  • Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV push once on day 1
      • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Cyclophosphamide (Cytoxan) 1200 mg/m2 IV over 60 minutes once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, VC portion Regimen B1 (cycle 13; Surgery Only)

  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m2
    • Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

Chemotherapy, VDC portion Regimen B2 & B3 (cycle 13; Radiation w/ or w/o Surgery)

  • Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV push once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Doxorubicin (Adriamycin) 75 mg/m2 IV continuous infusion over 48 hours, started on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated
  • Cyclophosphamide (Cytoxan) 1200 mg/m2 IV over 60 minutes once on day 1
    • Treat with 50% doses calculated on a m2 basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated

Supportive therapy, VDC portion Regimen B2 & B3 (cycle 13; Radiation w/ or w/o Surgery)

  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
    • NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m2
    • Continuous infusion should be started at the same time as the cyclophosphamide and remain until at least 8 hours after the end of the cyclophosphamide infusion
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 7 days, or until ANC at least 750/μl, beginning on day 2
    • ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

14-day cycle for 8 cycles (14 cycles total)

References

  1. COG AEWS0031: Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, and Weiss AR. Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2012 Nov 20;30(33):4148-4154. Epub 2012 Oct 22. link to original article link to PMC article PubMed NCT00006734
    1. Update: Cash T, Krailo MD, Buxton AB, Pawel BR, Healey JH, Binitie O, Marcus KJ, Grier HE, Grohar PJ, Reed DR, Weiss AR, Gorlick R, Janeway KA, DuBois SG, Womer RB. Long-Term Outcomes in Patients With Localized Ewing Sarcoma Treated With Interval-Compressed Chemotherapy on Children's Oncology Group Study AEWS0031. J Clin Oncol. 2023 Oct 20;41(30):4724-4728. Epub 2023 Aug 31. link to original article PubMed
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