Ewing sarcoma, pediatric - historical

The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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 NCCN Guidelines. 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)	5/2001-8/2005	Phase 3 (C)	Intensified treatment	Seems to have inferior EFS

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

Induction

Chemotherapy, VDC portion (cycles 1 & 3)

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

Supportive therapy, VDC portion (cycles 1 & 3)

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

Chemotherapy, IE portion (cycles 2 & 4)

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

Supportive therapy, IE portion (cycles 2 & 4)

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

21-day cycle for 4 cycles, followed by:

Continuation

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

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

Chemotherapy, VDC portion (cycles 5 & 9)

Cycle 5 begins on week 15 in patients receiving surgery and on week 13 in Regimen A2

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

Supportive medication, VDC portion (cycles 5 & 9)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Chemotherapy, VC portion (cycle 13)

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

Supportive therapy, VC portion (cycle 13)

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

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

References

1. COG AEWS0031: Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, and Weiss AR. Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2012 Nov 20;30(33):4148-4154. Epub 2012 Oct 22. link to original article link to PMC article PubMed NCT00006734

COG AEWS0031 Protocol B

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Womer et al. 2012 (COG AEWS0031)	5/2001-8/2005	Phase 3 (E-esc)	Standard treatment	Seems to have superior EFS (primary endpoint) EFS60: 73% vs 65% (HR 0.74, 95% CI 0.54-0.99) Seems to have superior OS (secondary endpoint) OS60: 83% vs 77% (HR 0.69, 95% CI 0.47-1.00)

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

Induction

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

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

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

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

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

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

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

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

14-day cycle for 6 cycles, followed by:

Continuation

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

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

Chemotherapy, VDC portion (cycle 7)

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

Supportive therapy, VDC portion (cycle 7)

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

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

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

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

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

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

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

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

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

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

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

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

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

Chemotherapy, VC portion (cycle 11)

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

Supportive therapy, VC portion (cycle 11)

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

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

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

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

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

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

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

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

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

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

References

1. COG AEWS0031: Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, and Weiss AR. Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2012 Nov 20;30(33):4148-4154. Epub 2012 Oct 22. link to original article link to PMC article PubMed NCT00006734