Ewing sarcoma, pediatric - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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

  • 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:
  • 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

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
  • 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:


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

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:
  • 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

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
  • 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

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:
  • 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

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:
  • 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

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:
  • 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, 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:
  • 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/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:
  • 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)

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 Clinical Trial Registry

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

  • 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:
  • 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

Chemotherapy, IE portion

  • Ifosfamide (Ifex) as follows:
    • Cycles 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:
    • Cycles 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:
    • Cycles 2, 4, 6: 1080 mg/m2 IV continuous infusion on day 1
  • 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:


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

  • 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:
  • 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

Chemotherapy, IE portion

  • Ifosfamide (Ifex) as follows:
    • Cycles 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:
    • Cycles 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:
    • Cycles 8, 10, 12, 14: 1080 mg/m2 IV continuous infusion on day 1
  • Filgrastim (Neupogen) as follows:
    • Cycles 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

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:
  • 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 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:
  • 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/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:
  • 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 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:
  • 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 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:
  • 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 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 Clinical Trial Registry
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