Ewing Sarcoma, pediatric

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Chandni Dargan, MD
Kansas City, MO
University of Missouri

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Upfront Therapy

COG AEWS0031

Regimen A Induction

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

Cycles 1 & 3 (VDC)

  • Vincristine (Oncovin) 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) 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) 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
  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Cycles 2 & 4 (IE)

  • Ifosfamide (Ifex) 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) 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
  • Mesna (Mesnex) 1080 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Regimen A Continuation

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

Cycle 5 & 9 (VDC)

Cycle 5 begins on week 15 in patients receiving surgery and on week 13 in Regimen A2
  • Vincristine (Oncovin) 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) 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) 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
  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Cycle 6, 8, 10, 12, & 14 (IE)

  • Ifosfamide (Ifex) 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) 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
  • Mesna (Mesnex) 1080 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Cycle 7 (VDC) Regimen A1 (Surgery Only)

  • Vincristine (Oncovin) 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) 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) 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
  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Cycle 7 (VC) Regimen A2 & A3 (Radiation w/ or w/o Surgery)

  • Vincristine (Oncovin) 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) 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
  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Cycle 11 (VC) Regimen A1 (Surgery Only)

  • Vincristine (Oncovin) 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) 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
  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Cycle 11 (VDC) Regimen A2 & A3 (Radiation w/ or w/o Surgery)

  • Vincristine (Oncovin) 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) 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) 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
  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Cycle 13 (VC)

  • Vincristine (Oncovin) 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) 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
  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Regimen B Induction

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

Cycles 1, 3, & 5 (VDC)

  • Vincristine (Oncovin) 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) 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) 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
  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Cycle 2, 4, & 6 (IE)

  • Ifosfamide (Ifex) 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) 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
  • Mesna (Mesnex) 1080 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Regimen B Continuation

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

Cycle 7 (VDC)

Cycle 7 begins on week 15 in patients receiving surgery and on week 13 in Regimen B2
  • Vincristine (Oncovin) 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) 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) 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
  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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


Cycle 8, 10, 12, & 14 (IE)

  • Ifosfamide (Ifex) 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) 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
  • Mesna (Mesnex) 1080 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Cycle 9 (VDC) Regimen B1 (Surgery Only)

  • Vincristine (Oncovin) 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) 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) 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
  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Cycle 9 (VC) Regimen B2 & B3 (Radiation w/ or w/o Surgery)

  • Vincristine (Oncovin) 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) 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
  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Cycle 11 (VC)

  • Vincristine (Oncovin) 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) 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
  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Cycle 13 (VC) Regimen B1 (Surgery Only)

  • Vincristine (Oncovin) 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) 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
  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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

Cycle 13 (VDC) Regimen B2 & B3 (Radiation w/ or w/o Surgery)

  • Vincristine (Oncovin) 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) 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) 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
  • Mesna (Mesnex) 720 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) 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. link to original article link to PMC article PubMed NCT00006734


COG AEWS1031

Regimen A Induction

  • Regimen A is a standard regimen consisting of 14 day cycles

Cycles 1, 3, & 5 (VDC)

  • Vincristine (Oncovin) 1.5 mg/m2/dose IV push once on day 1 of weeks 1, 2, 5, 6, 9 & 10 (maximum dose of 2 mg)
    • For children < 10 kg or < 1 year, the dose is 0.05 mg/kg/dose
  • Doxorubicin (Adriamycin) 37.5 mg/m2/dose IV push/infusion over 1-15 minutes on days 1 and 2 of weeks 1, 5 and 9.
    • For children < 10 kg or < 1 year, the dose is 1.25 mg/kg/dose
    • Administer at a concentration not to exceed 2 mg/mL. Doxorubicin (Adriamycin) should be administered through the tubing of rapidly infusing solution of D5W or 0.9% NaCl, and it should not be infused into a large vein
  • Cyclophosphamide (Cytoxan) 1200 mg/m2/dose IV over 30 to60 minutes on day 1 of weeks 1, 5 and 9
    • For children < 10 kg or < 1 year, the dose is 40 mg/kg/dose
    • May be administered as undiluted drug (20 mg/mL, reconstitute with 0.9% NaCl to avoid hypotonic solution) or further diluted
  • Mesna (Mesnex) 720 mg/m2/day by IV infusion or IV/PO with Cyclophosphamide (Cytoxan) on day 1 of weeks 1, 5 and 9
    • For children < 10 kg or < 1 year, the dose is 24 mg/kg/dose

14 day cycle

Cycles 2, 4, & 6 (IE)

  • Ifosfamide (Ifex) 1,800 mg/m2/dose IV infusion over 1 hour on days 1, 2, 3, 4, and 5 of Weeks 3, 7 and 11
    • For children < 10 kg or < 1 year, the dose is 60 mg/kg/dose
    • Achieve urine specific gravity ≤ 1.010 prior to start of Ifosfamide (Ifex).
  • Mesna (Mesnex) 1,080 mg/m2/day by IV infusion or IV/PO with Ifosfamide (Ifex) on days 1, 2, 3, 4, and 5 of Weeks 3, 7 and 11
    • For children < 10 kg or < 1 year, the dose is 36 mg/kg/dose
  • Etoposide (Vepesid) 100 mg/m2/dose IV infusion over 1 to 2 hours once on days 1, 2, 3, 4, and 5 of weeks 3, 7 and 11
    • For children < 10 kg or < 1 year, the dose is 3.3 mg/kg/dose

14 day cycle

Regimen A Consolidation

Regimen B Induction

Regimen B Consolidation