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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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

Induction

• Regimen A is a standard regimen consisting of 21-day cycles

Chemotherapy, VDC portion

• Vincristine (Oncovin) as follows:
  • Cycles 1 & 3: 2 mg/m² IV push once on day 1 (maximum dose of 2 mg)
    • 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) as follows:
  • Cycles 1 & 3: 75 mg/m² IV infusion over 48 hours 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) as follows:
  • Cycles 1 & 3: 1200 mg/m² IV over 1 hour on Days 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

• Mesna (Mesnex) as follows:
  • Cycles 1 & 3: 720 mg/m² IV continuous infusion on day 1
    • NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m²
    • Mesna (Mesnex) continuous infusion should be started at the same time as the Cyclophosphamide (Cytoxan) and remain until at least 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion
• Filgrastim (Neupogen) as follows:
  • Cycles 1 & 3: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
    • ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

21-day cycle

Chemotherapy, IE portion

• Ifosfamide (Ifex) as follows:
  • Cycles 2 & 4: 1800 mg/m² IV infusion over 1 hour once on day 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) as follows:
  • Cycles 2 & 4: 100 mg/m² IV infusion over 1 to 2 hours once 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

• Mesna (Mesnex) as follows:
  • Cycles 2 & 4: 1080 mg/m² IV continuous infusion on day 1
    • NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Ifosfamide (Ifex) m²
    • Mesna (Mesnex) continuous infusion should be started at the same time as the Ifosfamide (Ifex) and remain until at least 8 hours after the end of the Ifosfamide (Ifex) infusion
• 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

Continuation

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

Chemotherapy, VDC portion

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

• Vincristine (Oncovin) as follows:
  • Cycle 5 & 9: 2 mg/m² IV push once on day 1 (maximum dose of 2 mg)
    • 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) as follows:
  • Cycle 5 & 9: 75 mg/m² IV infusion over 48 hours 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) as follows:
  • Cycle 5 & 9: 1200 mg/m² IV over 1 hour on Days 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

• Mesna (Mesnex) as follows:
  • Cycle 5 & 9: 720 mg/m² IV continuous infusion on day 1
    • NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m²
    • Mesna (Mesnex) continuous infusion should be started at the same time as the Cyclophosphamide (Cytoxan) and remain until at least 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion
• Filgrastim (Neupogen) as follows:
  • Cycle 5 & 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

21-day cycle

Chemotherapy, IE portion

• Ifosfamide (Ifex) as follows:
  • Cycle 6, 8, 10, 12, & 14: 1800 mg/m² IV infusion over 1 hour once on day 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) as follows:
  • Cycle 6, 8, 10, 12, & 14: 100 mg/m² IV infusion over 1 to 2 hours once 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

• Mesna (Mesnex) as follows:
  • Cycle 6, 8, 10, 12, & 14: 1080 mg/m² IV continuous infusion on day 1
    • NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Ifosfamide (Ifex) m²
    • Mesna (Mesnex) continuous infusion should be started at the same time as the Ifosfamide (Ifex) and remain until at least 8 hours after the end of the Ifosfamide (Ifex) infusion
• Filgrastim (Neupogen) as follows:
  • Cycle 6, 8, 10, 12, & 14: 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

Chemotherapy, VDC portion Regimen A₁ (Surgery Only)

• Vincristine (Oncovin) as follows:
  • Cycle 7: 2 mg/m² IV push once on day 1 (maximum dose of 2 mg)
    • 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) as follows:
  • Cycle 7: 75 mg/m² IV infusion over 48 hours 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) as follows:
  • Cycle 7: 1200 mg/m² IV over 1 hour on Days 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 (Surgery Only)

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

21-day cycle

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

• Vincristine (Oncovin) as follows:
  • Cycle 7: 2 mg/m² IV push once on day 1 (maximum dose of 2 mg)
    • 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) as follows:
  • Cycle 7: 1200 mg/m² IV over 1 hour on Days 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 (Radiation w/ or w/o Surgery)

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

21-day cycle

Chemotherapy, VC portion Regimen A₁ (Surgery Only)

• Vincristine (Oncovin) as follows:
  • Cycle 11: 2 mg/m² IV push once on day 1 (maximum dose of 2 mg)
    • 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) as follows:
  • Cycle 11: 1200 mg/m² IV over 1 hour on Days 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 (Surgery Only)

• Mesna (Mesnex) as follows:
  • Cycle 11: 720 mg/m² IV continuous infusion on day 1
    • NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m²
    • Mesna (Mesnex) continuous infusion should be started at the same time as the Cyclophosphamide (Cytoxan) and remain until at least 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion
• Filgrastim (Neupogen) as follows:
  • Cycle 11: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
    • ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

21-day cycle

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

• Vincristine (Oncovin) as follows:
  • Cycle 11: 2 mg/m² IV push once on day 1 (maximum dose of 2 mg)
    • 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) as follows:
  • Cycle 11: 75 mg/m² IV infusion over 48 hours 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) as follows:
  • Cycle 11: 1200 mg/m² IV over 1 hour on Days 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 (Radiation w/ or w/o Surgery)

• Mesna (Mesnex) as follows:
  • Cycle 11: 720 mg/m² IV continuous infusion on day 1
    • NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m²
    • Mesna (Mesnex) continuous infusion should be started at the same time as the Cyclophosphamide (Cytoxan) and remain until at least 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion
• Filgrastim (Neupogen) as follows:
  • Cycle 11: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
  • ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

21-day cycle

Chemotherapy, VC portion

• Vincristine (Oncovin) as follows:
  • Cycle 13: 2 mg/m² IV push once on day 1 (maximum dose of 2 mg)
    • 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) as follows:
  • Cycle 13: 1200 mg/m² IV over 1 hour on Days 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

• Mesna (Mesnex) as follows:
  • Cycle 13: 720 mg/m² IV continuous infusion on day 1
    • NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m²
    • Mesna (Mesnex) continuous infusion should be started at the same time as the Cyclophosphamide (Cytoxan) and remain until at least 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion
• Filgrastim (Neupogen) as follows:
  • Cycle 13: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
    • ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

21-day cycle

References

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	Years 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)

Induction

• Regimen B is a consolidated regimen consisting of 14-day cycles

Chemotherapy, VDC portion

• Vincristine (Oncovin) as follows:
  • Cycles 1, 3, & 5: 2 mg/m² IV push once on day 1 (maximum dose of 2 mg)
    • 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) as follows:
  • Cycles 1, 3, & 5: 75 mg/m² IV infusion over 48 hours 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) as follows:
  • Cycles 1, 3, & 5: 1200 mg/m² IV over 1 hour on Days 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

• Mesna (Mesnex) as follows:
  • Cycles 1, 3, & 5: 720 mg/m² IV continuous infusion on day 1
    • NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m²
    • Mesna (Mesnex) continuous infusion should be started at the same time as the Cyclophosphamide (Cytoxan) and remain until at least 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion
• Filgrastim (Neupogen) as follows:
  • Cycles 1, 3, & 5: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
    • ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

14-day cycle

Chemotherapy, IE portion

• Ifosfamide (Ifex) as follows:
  • Cycle 2, 4, & 6: 1800 mg/m² IV infusion over 1 hour once on day 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) as follows:
  • Cycle 2, 4, & 6: 100 mg/m² IV infusion over 1 to 2 hours once 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

• Mesna (Mesnex) as follows:
  • Cycle 2, 4, & 6: 1080 mg/m² IV continuous infusion on day 1
    • NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Ifosfamide (Ifex) m²
    • Mesna (Mesnex) continuous infusion should be started at the same time as the Ifosfamide (Ifex) and remain until at least 8 hours after the end of the Ifosfamide (Ifex) infusion
• Filgrastim (Neupogen) as follows:
  • Cycle 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

Continuation

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

Chemotherapy, VDC portion

Cycle 7 begins on week 15 in patients receiving surgery and on week 13 in Regimen B2

• Vincristine (Oncovin) as follows:
  • Cycle 7: 2 mg/m² IV push once on day 1 (maximum dose of 2 mg)
    • 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) as follows:
  • Cycle 7: 75 mg/m² IV infusion over 48 hours 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) as follows:
  • Cycle 7: 1200 mg/m² IV over 1 hour on Days 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

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

14-day cycle

Chemotherapy, IE portion

• Ifosfamide (Ifex) as follows:
  • Cycle 8, 10, 12, & 14: 1800 mg/m² IV infusion over 1 hour once on day 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) as follows:
  • Cycle 8, 10, 12, & 14: 100 mg/m² IV infusion over 1 to 2 hours once 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

• Mesna (Mesnex) as follows:
  • Cycle 8, 10, 12, & 14: 1080 mg/m² IV continuous infusion on day 1
    • NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Ifosfamide (Ifex) m²
    • Mesna (Mesnex) continuous infusion should be started at the same time as the Ifosfamide (Ifex) and remain until at least 8 hours after the end of the Ifosfamide (Ifex) infusion
• Filgrastim (Neupogen) as follows:
  • Cycle 8, 10, 12, & 14: 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

Chemotherapy, VDC portion Regimen B₁ (Surgery Only)

• Vincristine (Oncovin) as follows:
  • Cycle 9: 2 mg/m² IV push once on day 1 (maximum dose of 2 mg)
    • 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) as follows:
  • Cycle 9: 75 mg/m² IV infusion over 48 hours 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) as follows:
  • Cycle 9: 1200 mg/m² IV over 1 hour on Days 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 (Surgery Only)

• Mesna (Mesnex) as follows:
  • Cycle 9: 720 mg/m² IV continuous infusion on day 1
    • NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m²
    • Mesna (Mesnex) continuous infusion should be started at the same time as the Cyclophosphamide (Cytoxan) and remain until at least 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion
• Filgrastim (Neupogen) as follows:
  • Cycle 9: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
    • ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

14-day cycle

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

• Vincristine (Oncovin) as follows:
  • Cycle 9: 2 mg/m² IV push once on day 1 (maximum dose of 2 mg)
    • 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) as follows:
  • Cycle 9: 1200 mg/m² IV over 1 hour on Days 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 (Radiation w/ or w/o Surgery)

• Mesna (Mesnex) as follows:
  • Cycle 9: 720 mg/m² IV continuous infusion on day 1
    • NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m²
    • Mesna (Mesnex) continuous infusion should be started at the same time as the Cyclophosphamide (Cytoxan) and remain until at least 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion
• Filgrastim (Neupogen) as follows:
  • Cycle 9: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
    • ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

14-day cycle

Chemotherapy, VC portion

• Vincristine (Oncovin) as follows:
  • Cycle 11: 2 mg/m² IV push once on day 1 (maximum dose of 2 mg)
    • 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) as follows:
  • Cycle 11: 1200 mg/m² IV over 1 hour on Days 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

• Mesna (Mesnex) as follows:
  • Cycle 11: 720 mg/m² IV continuous infusion on day 1
    • NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m²
    • Mesna (Mesnex) continuous infusion should be started at the same time as the Cyclophosphamide (Cytoxan) and remain until at least 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion
• Filgrastim (Neupogen) as follows:
  • Cycle 11: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
    • ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

14-day cycle

Chemotherapy, VC portion Regimen B₁ (Surgery Only)

• Vincristine (Oncovin) as follows:
  • Cycle 13: 2 mg/m² IV push once on day 1 (maximum dose of 2 mg)
    • 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) as follows:
  • Cycle 13: 1200 mg/m² IV over 1 hour on Days 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 (Surgery Only)

• Mesna (Mesnex) as follows:
  • Cycle 13: 720 mg/m² IV continuous infusion on day 1
    • NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m²
    • Mesna (Mesnex) continuous infusion should be started at the same time as the Cyclophosphamide (Cytoxan) and remain until at least 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion
• Filgrastim (Neupogen) as follows:
  • Cycle 13: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
    • ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

14-day cycle

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

• Vincristine (Oncovin) as follows:
  • Cycle 13: 2 mg/m² IV push once on day 1 (maximum dose of 2 mg)
    • 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) as follows:
  • Cycle 13: 75 mg/m² IV infusion over 48 hours 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) as follows:
  • Cycle 13: 1200 mg/m² IV over 1 hour on Days 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 (Radiation w/ or w/o Surgery)

• Mesna (Mesnex) as follows:
  • Cycle 13: 720 mg/m² IV continuous infusion on day 1
    • NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m²
    • Mesna (Mesnex) continuous infusion should be started at the same time as the Cyclophosphamide (Cytoxan) and remain until at least 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion
• Filgrastim (Neupogen) as follows:
  • Cycle 13: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
    • ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

14-day cycle

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