Ewing sarcoma, pediatric - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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.
Last updated on 2024-07-23:2 regimens on this page
2 variants on this page
=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 shorter 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===
#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 EuroPMC 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. link to original article link to PMC article EuroPMC
==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 longer EFS (primary endpoint)EFS60: 73% vs 65%(HR 0.74, 95% CI 0.54-0.99)Seems to have longer 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===
#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 EuroPMC 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. link to original article link to PMC article EuroPMC
Category:Ewing sarcoma regimens
Category:Historical regimens
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Category:Bone sarcomas
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