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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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

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 link to PMC 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

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 link to PMC article PubMed

@@ Line 3: / Line 3: @@
 [[#top|Back to Top]]
 </div>
-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.
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
@@ Line 21: / Line 21: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494838/ Womer et al. 2012 (COG AEWS0031)]
-|5/2001-8/2005
+|2001-05 to 2005-08
 | style="background-color:#1a9851" |Phase 3 (C)
 |[[#COG_AEWS0031_Protocol_B|Intensified treatment]]
@@ Line 28: / Line 28: @@
 |}
 ''Protocol A is a standard protocol consisting of 14 21-day cycles''
-<div class="toccolours" style="background-color:#eeeeee">
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Induction===
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy, VDC portion====
+====Chemotherapy, VDC portion (cycles 1 & 3)====
-*[[Vincristine (Oncovin)]] as follows:
+*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
-**Cycles 1 & 3: 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
-**Cycles 1 & 3: 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, VDC portion (cycles 1 & 3)====
-**Cycles 1 & 3: 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====
+**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
-**Cycles 1 & 3: 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 m<sup>2</sup>
+====Chemotherapy, IE portion (cycles 2 & 4)====
-***[[Mesna (Mesnex)]] 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
+*[[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
-**Cycles 1 & 3: 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
-====Chemotherapy, IE portion====
+====Supportive therapy, IE portion (cycles 2 & 4)====
-*[[Ifosfamide (Ifex)]] as follows:
+*[[Mesna (Mesnex)]] 1080 mg/m<sup>2</sup> IV continuous infusion on day 1
-**Cycles 2 & 4: 1800 mg/m<sup>2</sup> IV infusion over 1 hour once on day 1 to 5
+**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide 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
+**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
-*[[Etoposide (Vepesid)]] 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 6
-**Cycles 2 & 4: 100 mg/m<sup>2</sup> IV infusion over 1 to 2 hours once on days 1 to 5
+**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
-====Supportive therapy, IE portion====
-*[[Mesna (Mesnex)]] as follows:
-**Cycles 2 & 4: 1080 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 ifosfamide m<sup>2</sup>
-***[[Mesna (Mesnex)]] 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)]] as follows:
-**Cycles 2 & 4: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6
-***ANC ≥ 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:#eeeeee">
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Continuation===
 *At week 13 patients either underwent surgery, received radiation, or both
@@ Line 72: / Line 63: @@
 ''Note: the cycle count for this phase starts at cycle 5.''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy, VDC portion====
+====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>
-*[[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 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 and remain until at least 8 hours after the end of the cyclophosphamide 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
-====Chemotherapy, IE portion====
+====Supportive therapy, IE portion (cycles 6, 8, 10, 12, 14)====
-*[[Ifosfamide (Ifex)]] as follows:
+*[[Mesna (Mesnex)]] 1080 mg/m<sup>2</sup> IV continuous infusion on day 1
-**Cycle 6, 8, 10, 12, & 14: 1800 mg/m<sup>2</sup> IV infusion over 1 hour once on day 1 to 5
+**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide 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 ifosfamide and remain until at least 8 hours after the end of the ifosfamide infusion
-*[[Etoposide (Vepesid)]] 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 6
-**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
+**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, VDC portion Regimen A<sub>1</sub> (cycle 7; Surgery Only)====
-====Supportive therapy, IE portion====
+*[[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 6, 8, 10, 12, & 14: 1080 mg/m<sup>2</sup> IV continuous infusion on day 1
+*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV continuous infusion over 48 hours, started on day 1
-***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of ifosfamide 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 ifosfamide and remain until at least 8 hours after the end of the ifosfamide infusion
+*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes 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 6, 8, 10, 12, & 14: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6
+====Supportive therapy, VDC portion Regimen A<sub>1</sub> (cycle 7; Surgery Only)====
-***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
-====Chemotherapy, VDC portion Regimen A<sub>1</sub> (Surgery Only)====
+**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
-*[[Vincristine (Oncovin)]] 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 7: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
+*[[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
-*[[Doxorubicin (Adriamycin)]] as follows:
+====Chemotherapy, VC portion Regimen A<sub>2</sub> & A<sub>3</sub> (cycle 7; Radiation w/ or w/o Surgery)====
-**Cycle 7: 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1
+*[[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
+**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:
+*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-**Cycle 7: 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
-***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 A<sub>2</sub> & A<sub>3</sub> (cycle 7; Radiation w/ or w/o Surgery)====
-====Supportive therapy, VDC portion Regimen A<sub>1</sub> (Surgery Only)====
+*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
-*[[Mesna (Mesnex)]] as follows:
+**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
-**Cycle 7: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
+**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
-***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
+*[[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)]] 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
+**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
-*[[Filgrastim (Neupogen)]] as follows:
+====Chemotherapy, VC portion Regimen A<sub>1</sub> (cycle 11; Surgery Only)====
-**Cycle 7: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
+*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push 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
-====Chemotherapy, VC portion Regimen A<sub>2</sub> & A<sub>3</sub> (Radiation w/ or w/o Surgery)====
+*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes 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)
+====Supportive therapy, VC portion Regimen A<sub>1</sub> (cycle 11; 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
+*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
-*[[Cyclophosphamide (Cytoxan)]] as follows:
+**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
-**Cycle 7: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
+**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
-====Supportive therapy, VC portion Regimen A<sub>2</sub> & A<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
-*[[Mesna (Mesnex)]] as follows:
+====Chemotherapy, VDC portion Regimen A<sub>2</sub> & A<sub>3</sub> (cycle 11; Radiation w/ or w/o Surgery)====
-**Cycle 7: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
+*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
-***NOTE: Protocol states that [[Mesna (Mesnex)]] 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
-***[[Mesna (Mesnex)]] 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
+*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV continuous infusion over 48 hours, started 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
-====Chemotherapy, VC portion Regimen A<sub>1</sub> (Surgery Only)====
+====Supportive therapy, VDC portion Regimen A<sub>2</sub> & A<sub>3</sub> (cycle 11; Radiation w/ or w/o Surgery)====
-*[[Vincristine (Oncovin)]] as follows:
+*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
-**Cycle 11: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
+**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 11: 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 13)====
-====Supportive therapy, VC portion Regimen A<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 11: 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 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 and remain until at least 8 hours after the end of the cyclophosphamide infusion
+====Supportive therapy, VC portion (cycle 13)====
-*[[Filgrastim (Neupogen)]] as follows:
+*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
-**Cycle 11: 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
-====Chemotherapy, VDC portion Regimen A<sub>2</sub> & A<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
-*[[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)
-***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 therapy, 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 m<sup>2</sup>
-***[[Mesna (Mesnex)]] 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)]] 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
-====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 therapy, 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 m<sup>2</sup>
-***[[Mesna (Mesnex)]] 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)]] 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 for 9 cycles (13 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602538/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37651654/ PubMed]
 ==COG AEWS0031 Protocol B==
 <div class="toccolours" style="background-color:#c8a2c8">
@@ Line 201: / Line 163: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494838/ Womer et al. 2012 (COG AEWS0031)]
-|5/2001-8/2005
+|2001-05 to 2005-08
 | style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[#COG_AEWS0031_Protocol_A|Standard treatment]]
@@ Line 208: / Line 170: @@
 |}
 ''Note: Protocol B is a consolidated regimen consisting of 14-day cycles.''
-<div class="toccolours" style="background-color:#eeeeee">
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Induction===
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy, VDC portion====
+====Chemotherapy, VDC portion (cycles 1, 3, 5)====
-*[[Vincristine (Oncovin)]] as follows:
+*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
-**Cycles 1, 3, 5: 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
-**Cycles 1, 3, 5: 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, VDC portion (cycles 1, 3, 5)====
-**Cycles 1, 3, 5: 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====
+**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
-**Cycles 1, 3, 5: 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 m<sup>2</sup>
+====Chemotherapy, IE portion (cycles 2, 4, 6)====
-***[[Mesna (Mesnex)]] 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
+*[[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
-**Cycles 1, 3, 5: 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
-====Chemotherapy, IE portion====
+====Supportive therapy, IE portion (cycles 2, 4, 6)====
-*[[Ifosfamide (Ifex)]] as follows:
+*[[Mesna (Mesnex)]] 1080 mg/m<sup>2</sup> IV continuous infusion on day 1
-**Cycles 2, 4, 6: 1800 mg/m<sup>2</sup> IV infusion over 1 hour once on day 1 to 5
+**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide 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 ifosfamide and remain until at least 8 hours after the end of the ifosfamide infusion
-*[[Etoposide (Vepesid)]] 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 6
-**Cycles 2, 4, 6: 100 mg/m<sup>2</sup> IV infusion over 1 to 2 hours once on days 1 to 5
+**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
-====Supportive therapy, IE portion====
-*[[Mesna (Mesnex)]] as follows:
-**Cycles 2, 4, 6: 1080 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 ifosfamide m<sup>2</sup>
-***[[Mesna (Mesnex)]] 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)]] as follows:
-**Cycles 2, 4, 6: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6
-***ANC ≥ 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:'''
 </div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Continuation===
 *At week 13 patients either underwent surgery, received radiation, or both
@@ Line 252: / Line 205: @@
 ''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)====
-*[[Vincristine (Oncovin)]] as follows:
+*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
-**Cycle 7: 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 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, VDC portion (cycle 7)====
-**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====
+**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 m<sup>2</sup>
+====Chemotherapy, IE portion (cycles 8, 10, 12, 14)====
-***[[Mesna (Mesnex)]] 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
+*[[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 7: 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
-====Chemotherapy, IE portion====
+====Supportive therapy, IE portion (cycles 8, 10, 12, 14)====
-*[[Ifosfamide (Ifex)]] as follows:
+*[[Mesna (Mesnex)]] 1080 mg/m<sup>2</sup> IV continuous infusion on day 1
-**Cycles 8, 10, 12, 14: 1800 mg/m<sup>2</sup> IV infusion over 1 hour once on day 1 to 5
+**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide 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 ifosfamide and remain until at least 8 hours after the end of the ifosfamide infusion
-*[[Etoposide (Vepesid)]] 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 6
-**Cycles 8, 10, 12, 14: 100 mg/m<sup>2</sup> IV infusion over 1 to 2 hours once on days 1 to 5
+**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, VDC portion Regimen B<sub>1</sub> (cycle 9; Surgery Only)====
-====Supportive therapy, IE portion====
+*[[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
-**Cycles 8, 10, 12, 14: 1080 mg/m<sup>2</sup> IV continuous infusion on day 1
+*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV continuous infusion over 48 hours, started on day 1
-***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of ifosfamide 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 ifosfamide and remain until at least 8 hours after the end of the ifosfamide infusion
+*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes 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 8, 10, 12, 14: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6
+====Supportive therapy, VDC portion Regimen B<sub>1</sub> (cycle 9; Surgery Only)====
-***ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
-====Chemotherapy, VDC portion Regimen B<sub>1</sub> (Surgery Only)====
+**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
-*[[Vincristine (Oncovin)]] 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 9: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
+*[[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
-*[[Doxorubicin (Adriamycin)]] as follows:
+====Chemotherapy, VC portion Regimen B<sub>2</sub> & B<sub>3</sub> (cycle 9; Radiation w/ or w/o Surgery)====
-**Cycle 9: 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1
+*[[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
+**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:
+*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-**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
-***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)====
-====Supportive therapy, VDC portion Regimen B<sub>1</sub> (Surgery Only)====
+*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1
-*[[Mesna (Mesnex)]] as follows:
+**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
-**Cycle 9: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
+**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
-***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
+*[[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)]] 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
+**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
-*[[Filgrastim (Neupogen)]] as follows:
+====Chemotherapy, VC portion (cycle 11)====
-**Cycle 9: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
+*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push 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
-====Chemotherapy, VC portion Regimen B<sub>2</sub> & B<sub>3</sub> (Radiation w/ or w/o Surgery)====
+*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 60 minutes 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 9: 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)
+====Supportive therapy, VC portion (cycle 11)====
-***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
-*[[Cyclophosphamide (Cytoxan)]] as follows:
+**NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
-**Cycle 9: 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1
+**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
-====Supportive therapy, 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
-*[[Mesna (Mesnex)]] as follows:
+====Chemotherapy, VC portion Regimen B<sub>1</sub> (cycle 13; Surgery Only)====
-**Cycle 9: 720 mg/m<sup>2</sup> IV continuous infusion on day 1
+*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once on day 1
-***NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of cyclophosphamide m<sup>2</sup>
-***[[Mesna (Mesnex)]] 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)]] 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
-====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 therapy, 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 m<sup>2</sup>
-***[[Mesna (Mesnex)]] 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)]] 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
-====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 therapy, 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 m<sup>2</sup>
-***[[Mesna (Mesnex)]] 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)]] 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
-====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
-*[[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 therapy, 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 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 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)]] 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
+**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 Regimen B<sub>2</sub> & B<sub>3</sub> (cycle 13; Radiation w/ or w/o Surgery)====
+*[[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://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602538/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37651654/ PubMed]
 [[Category:Ewing sarcoma regimens]]
 [[Category:Historical regimens]]

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

Latest revision as of 23:15, 6 July 2024

Upfront therapy, localized disease

COG AEWS0031 Protocol A

Induction

Chemotherapy, VDC portion (cycles 1 & 3)

Supportive therapy, VDC portion (cycles 1 & 3)

Chemotherapy, IE portion (cycles 2 & 4)

Supportive therapy, IE portion (cycles 2 & 4)

Continuation

Chemotherapy, VDC portion (cycles 5 & 9)

Supportive medication, VDC portion (cycles 5 & 9)

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

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

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

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

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

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

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

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

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

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

Chemotherapy, VC portion (cycle 13)

Supportive therapy, VC portion (cycle 13)

References

COG AEWS0031 Protocol B

Induction

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

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

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

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

Continuation

Chemotherapy, VDC portion (cycle 7)

Supportive therapy, VDC portion (cycle 7)

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

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

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

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

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

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

Chemotherapy, VC portion (cycle 11)

Supportive therapy, VC portion (cycle 11)

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

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

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

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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