# Ewing sarcoma, pediatric - historical

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#### Chemotherapy, VDC portion Regimen A

#### Supportive therapy, VDC portion Regimen A

#### Chemotherapy, VC portion Regimen A

#### Supportive therapy, VC portion Regimen A

#### Chemotherapy, VC portion Regimen A

#### Supportive therapy, VC portion Regimen A

#### Chemotherapy, VDC portion Regimen A

#### Supportive therapy, VDC portion Regimen A

#### Chemotherapy, VDC portion Regimen B

#### Supportive therapy, VDC portion Regimen B

#### Chemotherapy, VC portion Regimen B

#### Supportive therapy, VC portion Regimen B

#### Chemotherapy, VC portion Regimen B

#### Supportive therapy, VC portion Regimen B

#### Chemotherapy, VDC portion Regimen B

#### Supportive therapy, VDC portion Regimen B

The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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

0 regimens on this page0 variants on this page |

# 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/m
^{2}(maximum dose of 2 mg) IV push once on day 1- Treat with 50% doses calculated on a m
^{2}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
- Doxorubicin (Adriamycin) 75 mg/m
^{2}IV continuous infusion over 48 hours, started on day 1- Treat with 50% doses calculated on a m
^{2}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
- Cyclophosphamide (Cytoxan) 1200 mg/m
^{2}IV over 60 minutes once on day 1- Treat with 50% doses calculated on a m
^{2}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

#### Supportive therapy, VDC portion (cycles 1 & 3)

- Mesna (Mesnex) 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
^{2} - 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 should be dosed as AT LEAST 60% of cyclophosphamide m
- 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/m
^{2}IV infusion over 1 hour once per day on days 1 to 5- Treat with 50% doses calculated on a m
^{2}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
- Etoposide (Vepesid) 100 mg/m
^{2}IV infusion over 1 to 2 hours once per day on days 1 to 5- Treat with 50% doses calculated on a m
^{2}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

#### Supportive therapy, IE portion (cycles 2 & 4)

- Mesna (Mesnex) 1080 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m
^{2} - 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

- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m
- 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 A_{2}

- Vincristine (Oncovin) 2 mg/m
^{2}(maximum dose of 2 mg) IV push once on day 1- Treat with 50% doses calculated on a m
^{2}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
- Doxorubicin (Adriamycin) 75 mg/m
^{2}IV continuous infusion over 48 hours, started on day 1- Treat with 50% doses calculated on a m
^{2}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
- Cyclophosphamide (Cytoxan) 1200 mg/m
^{2}IV over 60 minutes once on day 1- Treat with 50% doses calculated on a m
^{2}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

#### Supportive medication, VDC portion (cycles 5 & 9)

- Mesna (Mesnex) 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
^{2} - 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 should be dosed as AT LEAST 60% of cyclophosphamide m
- 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/m
^{2}IV infusion over 1 hour once per day on days 1 to 5- Treat with 50% doses calculated on a m
^{2}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
- Etoposide (Vepesid) 100 mg/m
^{2}IV infusion over 1 to 2 hours once per day on days 1 to 5- Treat with 50% doses calculated on a m
^{2}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

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

- Mesna (Mesnex) 1080 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m
^{2} - 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

- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m
- 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 A_{1} (cycle 7; Surgery Only)

- Vincristine (Oncovin) 2 mg/m
^{2}(maximum dose of 2 mg) IV push once on day 1- Treat with 50% doses calculated on a m
^{2}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
- Doxorubicin (Adriamycin) 75 mg/m
^{2}IV continuous infusion over 48 hours, started on day 1- Treat with 50% doses calculated on a m
^{2}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
- Cyclophosphamide (Cytoxan) 1200 mg/m
^{2}IV over 60 minutes once on day 1- Treat with 50% doses calculated on a m
^{2}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

#### Supportive therapy, VDC portion Regimen A_{1} (cycle 7; Surgery Only)

- Mesna (Mesnex) 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
^{2} - 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 should be dosed as AT LEAST 60% of cyclophosphamide m
- 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 A_{2} & A_{3} (cycle 7; Radiation w/ or w/o Surgery)

- Vincristine (Oncovin) 2 mg/m
^{2}(maximum dose of 2 mg) IV push once on day 1- Treat with 50% doses calculated on a m
^{2}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
- Cyclophosphamide (Cytoxan) 1200 mg/m
^{2}IV over 60 minutes once on day 1- Treat with 50% doses calculated on a m
^{2}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

#### Supportive therapy, VC portion Regimen A_{2} & A_{3} (cycle 7; Radiation w/ or w/o Surgery)

- Mesna (Mesnex) 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
^{2}

- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
- 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 A_{1} (cycle 11; Surgery Only)

- Vincristine (Oncovin) 2 mg/m
^{2}(maximum dose of 2 mg) IV push once on day 1- Treat with 50% doses calculated on a m
^{2}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
- Cyclophosphamide (Cytoxan) 1200 mg/m
^{2}IV over 60 minutes once on day 1- Treat with 50% doses calculated on a m
^{2}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

#### Supportive therapy, VC portion Regimen A_{1} (cycle 11; Surgery Only)

- Mesna (Mesnex) 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
^{2}

- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
- 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 A_{2} & A_{3} (cycle 11; Radiation w/ or w/o Surgery)

- Vincristine (Oncovin) 2 mg/m
^{2}(maximum dose of 2 mg) IV push once on day 1- Treat with 50% doses calculated on a m
^{2}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
- Doxorubicin (Adriamycin) 75 mg/m
^{2}IV continuous infusion over 48 hours, started on day 1- Treat with 50% doses calculated on a m
^{2}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
- Cyclophosphamide (Cytoxan) 1200 mg/m
^{2}IV over 60 minutes once on day 1- Treat with 50% doses calculated on a m
^{2}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

#### Supportive therapy, VDC portion Regimen A_{2} & A_{3} (cycle 11; Radiation w/ or w/o Surgery)

- Mesna (Mesnex) 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
^{2}

- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
- 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/m
^{2}(maximum dose of 2 mg) IV push once on day 1- Treat with 50% doses calculated on a m
^{2}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
- Cyclophosphamide (Cytoxan) 1200 mg/m
^{2}IV over 60 minutes once on day 1- Treat with 50% doses calculated on a m
^{2}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

#### Supportive therapy, VC portion (cycle 13)

- Mesna (Mesnex) 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
^{2}

- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
- 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**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 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/m
^{2}(maximum dose of 2 mg) IV push once on day 1- Treat with 50% doses calculated on a m
^{2}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
- Doxorubicin (Adriamycin) 75 mg/m
^{2}IV continuous infusion over 48 hours, started on day 1- Treat with 50% doses calculated on a m
^{2}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
- Cyclophosphamide (Cytoxan) 1200 mg/m
^{2}IV over 60 minutes once on day 1- Treat with 50% doses calculated on a m
^{2}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

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

- Mesna (Mesnex) 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
^{2}

- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
- 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/m
^{2}IV infusion over 1 hour once per day on days 1 to 5- Treat with 50% doses calculated on a m
^{2}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
- Etoposide (Vepesid) 100 mg/m
^{2}IV infusion over 1 to 2 hours once per day on days 1 to 5- Treat with 50% doses calculated on a m
^{2}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

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

- Mesna (Mesnex) 1080 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m
^{2} - 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

- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m
- 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 B _{2}.*

#### Chemotherapy, VDC portion (cycle 7)

- Vincristine (Oncovin) 2 mg/m
^{2}(maximum dose of 2 mg) IV push once on day 1- Treat with 50% doses calculated on a m
^{2}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
- Doxorubicin (Adriamycin) 75 mg/m
^{2}IV continuous infusion over 48 hours, started on day 1- Treat with 50% doses calculated on a m
^{2}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
- Cyclophosphamide (Cytoxan) 1200 mg/m
^{2}IV over 60 minutes once on day 1- Treat with 50% doses calculated on a m
^{2}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

#### Supportive therapy, VDC portion (cycle 7)

- Mesna (Mesnex) 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
^{2}

- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
- 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/m
^{2}IV infusion over 1 hour once per day on days 1 to 5- Treat with 50% doses calculated on a m
^{2}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
- Etoposide (Vepesid) 100 mg/m
^{2}IV infusion over 1 to 2 hours once per day on days 1 to 5- Treat with 50% doses calculated on a m
^{2}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

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

- Mesna (Mesnex) 1080 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m
^{2} - 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

- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of ifosfamide m
- 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 B_{1} (cycle 9; Surgery Only)

- Vincristine (Oncovin) 2 mg/m
^{2}(maximum dose of 2 mg) IV push once on day 1- Treat with 50% doses calculated on a m
^{2}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
- Doxorubicin (Adriamycin) 75 mg/m
^{2}IV continuous infusion over 48 hours, started on day 1- Treat with 50% doses calculated on a m
^{2}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
- Cyclophosphamide (Cytoxan) 1200 mg/m
^{2}IV over 60 minutes once on day 1- Treat with 50% doses calculated on a m
^{2}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

#### Supportive therapy, VDC portion Regimen B_{1} (cycle 9; Surgery Only)

- Mesna (Mesnex) 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
^{2}

- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
- 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 B_{2} & B_{3} (cycle 9; Radiation w/ or w/o Surgery)

- Vincristine (Oncovin) 2 mg/m
^{2}(maximum dose of 2 mg) IV push once on day 1- Treat with 50% doses calculated on a m
^{2}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
- Cyclophosphamide (Cytoxan) 1200 mg/m
^{2}IV over 60 minutes once on day 1- Treat with 50% doses calculated on a m
^{2}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

#### Supportive therapy, VC portion Regimen B_{2} & B_{3} (cycle 9; Radiation w/ or w/o Surgery)

- Mesna (Mesnex) 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
^{2}

- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
- 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/m
^{2}(maximum dose of 2 mg) IV push once on day 1- Treat with 50% doses calculated on a m
^{2}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
- Cyclophosphamide (Cytoxan) 1200 mg/m
^{2}IV over 60 minutes once on day 1- Treat with 50% doses calculated on a m
^{2}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

#### Supportive therapy, VC portion (cycle 11)

- Mesna (Mesnex) 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
^{2}

- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
- 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 B_{1} (cycle 13; Surgery Only)

- Vincristine (Oncovin) 2 mg/m
^{2}(maximum dose of 2 mg) IV push once on day 1- Treat with 50% doses calculated on a m
^{2}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

- Cyclophosphamide (Cytoxan) 1200 mg/m
^{2}IV over 60 minutes once on day 1- Treat with 50% doses calculated on a m
^{2}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

#### Supportive therapy, VC portion Regimen B_{1} (cycle 13; Surgery Only)

- Mesna (Mesnex) 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
^{2}

- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
- 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 B_{2} & B_{3} (cycle 13; Radiation w/ or w/o Surgery)

- Vincristine (Oncovin) 2 mg/m
^{2}(maximum dose of 2 mg) IV push once on day 1- Treat with 50% doses calculated on a m
^{2}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
- Doxorubicin (Adriamycin) 75 mg/m
^{2}IV continuous infusion over 48 hours, started on day 1- Treat with 50% doses calculated on a m
^{2}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
- Cyclophosphamide (Cytoxan) 1200 mg/m
^{2}IV over 60 minutes once on day 1- Treat with 50% doses calculated on a m
^{2}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

#### Supportive therapy, VDC portion Regimen B_{2} & B_{3} (cycle 13; Radiation w/ or w/o Surgery)

- Mesna (Mesnex) 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
^{2}

- NOTE: Protocol states that mesna should be dosed as AT LEAST 60% of cyclophosphamide m
- 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**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 PubMed