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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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

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

## 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