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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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

### Regimen

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

#### Chemotherapy, VDC portion

- Vincristine (Oncovin) as follows:
- Cycles 1 & 3: 2 mg/m
^{2}IV push once on day 1 (maximum dose of 2 mg)- 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

- Cycles 1 & 3: 2 mg/m
- Doxorubicin (Adriamycin) as follows:
- Cycles 1 & 3: 75 mg/m
^{2}IV infusion over 48 hours 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

- Cycles 1 & 3: 75 mg/m
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 & 3: 1200 mg/m
^{2}IV over 1 hour on Days 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

- Cycles 1 & 3: 1200 mg/m

#### Supportive therapy, VDC portion

- Mesna (Mesnex) as follows:
- Cycles 1 & 3: 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m
^{2} - Mesna (Mesnex) continuous infusion should be started at the same time as the Cyclophosphamide (Cytoxan) and remain until at least 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m

- Cycles 1 & 3: 720 mg/m
- 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

- Cycles 1 & 3: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2

**21-day cycle**

#### Chemotherapy, IE portion

- Ifosfamide (Ifex) as follows:
- Cycles 2 & 4: 1800 mg/m
^{2}IV infusion over 1 hour once on day 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

- Cycles 2 & 4: 1800 mg/m
- Etoposide (Vepesid) as follows:
- Cycles 2 & 4: 100 mg/m
^{2}IV infusion over 1 to 2 hours once 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

- Cycles 2 & 4: 100 mg/m

#### Supportive therapy, IE portion

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

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Ifosfamide (Ifex) m

- Cycles 2 & 4: 1080 mg/m
- 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

- Cycles 2 & 4: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6

**21-day cycle**

### 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. link to original article link to PMC article PubMed NCT00006734

## COG AEWS0031 Continuation A

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

### Regimen

#### Chemotherapy, VDC portion

Cycle 5 begins on week 15 in patients receiving surgery and on week 13 in Regimen A_{2}

- Vincristine (Oncovin) as follows:
- Cycle 5 & 9: 2 mg/m
^{2}IV push once on day 1 (maximum dose of 2 mg)- 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

- Cycle 5 & 9: 2 mg/m
- Doxorubicin (Adriamycin) as follows:
- Cycle 5 & 9: 75 mg/m
^{2}IV infusion over 48 hours 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

- Cycle 5 & 9: 75 mg/m
- Cyclophosphamide (Cytoxan) as follows:
- Cycle 5 & 9: 1200 mg/m
^{2}IV over 1 hour on Days 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

- Cycle 5 & 9: 1200 mg/m

#### Supportive medication, VDC portion

- Mesna (Mesnex) as follows:
- Cycle 5 & 9: 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m
^{2} - Mesna (Mesnex) continuous infusion should be started at the same time as the Cyclophosphamide (Cytoxan) and remain until at least 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m

- Cycle 5 & 9: 720 mg/m
- 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

- Cycle 5 & 9: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2

**21-day cycle**

#### Chemotherapy, IE portion

- Ifosfamide (Ifex) as follows:
- Cycle 6, 8, 10, 12, & 14: 1800 mg/m
^{2}IV infusion over 1 hour once on day 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

- Cycle 6, 8, 10, 12, & 14: 1800 mg/m
- Etoposide (Vepesid) as follows:
- Cycle 6, 8, 10, 12, & 14: 100 mg/m
^{2}IV infusion over 1 to 2 hours once 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

- Cycle 6, 8, 10, 12, & 14: 100 mg/m

#### Supportive therapy, IE portion

- Mesna (Mesnex) as follows:
- Cycle 6, 8, 10, 12, & 14: 1080 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Ifosfamide (Ifex) m
^{2} - Mesna (Mesnex) continuous infusion should be started at the same time as the Ifosfamide (Ifex) and remain until at least 8 hours after the end of the Ifosfamide (Ifex) infusion

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Ifosfamide (Ifex) m

- Cycle 6, 8, 10, 12, & 14: 1080 mg/m
- 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

- Cycle 6, 8, 10, 12, & 14: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6

**21-day cycle**

#### Chemotherapy, VDC portion Regimen A_{1} (Surgery Only)

- Vincristine (Oncovin) as follows:
- Cycle 7: 2 mg/m
^{2}IV push once on day 1 (maximum dose of 2 mg)- 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

- Cycle 7: 2 mg/m
- Doxorubicin (Adriamycin) as follows:
- Cycle 7: 75 mg/m
^{2}IV infusion over 48 hours 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

- Cycle 7: 75 mg/m
- Cyclophosphamide (Cytoxan) as follows:
- Cycle 7: 1200 mg/m
^{2}IV over 1 hour on Days 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

- Cycle 7: 1200 mg/m

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

- Mesna (Mesnex) as follows:
- Cycle 7: 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m
^{2} - Mesna (Mesnex) continuous infusion should be started at the same time as the Cyclophosphamide (Cytoxan) and remain until at least 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m

- Cycle 7: 720 mg/m
- Filgrastim (Neupogen) as follows:
- Cycle 7: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
- ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

**21-day cycle**

#### Chemotherapy, VC portion Regimen A_{2} & A_{3} (Radiation w/ or w/o Surgery)

- Vincristine (Oncovin) as follows:
- Cycle 7: 2 mg/m
^{2}IV push once on day 1 (maximum dose of 2 mg)- 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

- Cycle 7: 2 mg/m
- Cyclophosphamide (Cytoxan) as follows:
- Cycle 7: 1200 mg/m
^{2}IV over 1 hour on Days 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

- Cycle 7: 1200 mg/m

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

- Mesna (Mesnex) as follows:
- Cycle 7: 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m
^{2}

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m

- Cycle 7: 720 mg/m
- Filgrastim (Neupogen) as follows:
- Cycle 7: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
- ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

**21-day cycle**

#### Chemotherapy, VC portion Regimen A_{1} (Surgery Only)

- Vincristine (Oncovin) as follows:
- Cycle 11: 2 mg/m
^{2}IV push once on day 1 (maximum dose of 2 mg)- 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

- Cycle 11: 2 mg/m
- Cyclophosphamide (Cytoxan) as follows:
- Cycle 11: 1200 mg/m
^{2}IV over 1 hour on Days 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

- Cycle 11: 1200 mg/m

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

- Mesna (Mesnex) as follows:
- Cycle 11: 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m
^{2}

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m

- Cycle 11: 720 mg/m
- 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

- Cycle 11: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2

**21-day cycle**

#### Chemotherapy, VDC portion Regimen A_{2} & A_{3} (Radiation w/ or w/o Surgery)

- Vincristine (Oncovin) as follows:
- Cycle 11: 2 mg/m
^{2}IV push once on day 1 (maximum dose of 2 mg)- 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

- Cycle 11: 2 mg/m
- Doxorubicin (Adriamycin) as follows:
- Cycle 11: 75 mg/m
^{2}IV infusion over 48 hours 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

- Cycle 11: 75 mg/m
- Cyclophosphamide (Cytoxan) as follows:
- Cycle 11: 1200 mg/m
^{2}IV over 1 hour on Days 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

- Cycle 11: 1200 mg/m

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

- Mesna (Mesnex) as follows:
- Cycle 11: 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m
^{2}

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m

- Cycle 11: 720 mg/m
- Filgrastim (Neupogen) as follows:
- Cycle 11: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2
- ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

**21-day cycle**

#### Chemotherapy, VC portion

- Vincristine (Oncovin) as follows:
- Cycle 13: 2 mg/m
^{2}IV push once on day 1 (maximum dose of 2 mg)- 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

- Cycle 13: 2 mg/m
- Cyclophosphamide (Cytoxan) as follows:
- Cycle 13: 1200 mg/m
^{2}IV over 1 hour on Days 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

- Cycle 13: 1200 mg/m

#### Supportive therapy, VC portion

- Mesna (Mesnex) as follows:
- Cycle 13: 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m
^{2}

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m

- Cycle 13: 720 mg/m
- 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

- Cycle 13: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2

**21-day cycle**

### 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. link to original article link to PMC article PubMed NCT00006734

## COG AEWS0031 Induction B

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

### Regimen

#### Chemotherapy, VDC portion

- Vincristine (Oncovin) as follows:
- Cycles 1, 3, & 5: 2 mg/m
^{2}IV push once on day 1 (maximum dose of 2 mg)- 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

- Cycles 1, 3, & 5: 2 mg/m
- Doxorubicin (Adriamycin) as follows:
- Cycles 1, 3, & 5: 75 mg/m
^{2}IV infusion over 48 hours 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

- Cycles 1, 3, & 5: 75 mg/m
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 1, 3, & 5: 1200 mg/m
^{2}IV over 1 hour on Days 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

- Cycles 1, 3, & 5: 1200 mg/m

#### Supportive therapy, VDC portion

- Mesna (Mesnex) as follows:
- Cycles 1, 3, & 5: 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m
^{2}

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m

- Cycles 1, 3, & 5: 720 mg/m
- 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

- Cycles 1, 3, & 5: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2

**14-day cycle**

#### Chemotherapy, IE portion

- Ifosfamide (Ifex) as follows:
- Cycle 2, 4, & 6: 1800 mg/m
^{2}IV infusion over 1 hour once on day 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

- Cycle 2, 4, & 6: 1800 mg/m
- Etoposide (Vepesid) as follows:
- Cycle 2, 4, & 6: 100 mg/m
^{2}IV infusion over 1 to 2 hours once 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

- Cycle 2, 4, & 6: 100 mg/m

#### Supportive therapy, IE portion

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

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Ifosfamide (Ifex) m

- Cycle 2, 4, & 6: 1080 mg/m
- Filgrastim (Neupogen) as follows:
- Cycle 2, 4, & 6: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6
- ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

- Cycle 2, 4, & 6: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6

**14-day cycle**

### 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. link to original article link to PMC article PubMed NCT00006734

## COG AEWS0031 Continuation B

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

### Regimen

#### Chemotherapy, VDC portion

Cycle 7 begins on week 15 in patients receiving surgery and on week 13 in Regimen B_{2}

- Vincristine (Oncovin) as follows:
- Cycle 7: 2 mg/m
^{2}IV push once on day 1 (maximum dose of 2 mg)- 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

- Cycle 7: 2 mg/m
- Doxorubicin (Adriamycin) as follows:
- Cycle 7: 75 mg/m
^{2}IV infusion over 48 hours 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

- Cycle 7: 75 mg/m
- Cyclophosphamide (Cytoxan) as follows:
- Cycle 7: 1200 mg/m
^{2}IV over 1 hour on Days 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

- Cycle 7: 1200 mg/m

#### Supportive therapy, VDC portion

- Mesna (Mesnex) as follows:
- Cycle 7: 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m
^{2}

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m

- Cycle 7: 720 mg/m
- 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

- Cycle 7: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2

**14-day cycle**

#### Chemotherapy, IE portion

- Ifosfamide (Ifex) as follows:
- Cycle 8, 10, 12, & 14: 1800 mg/m
^{2}IV infusion over 1 hour once on day 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

- Cycle 8, 10, 12, & 14: 1800 mg/m
- Etoposide (Vepesid) as follows:
- Cycle 8, 10, 12, & 14: 100 mg/m
^{2}IV infusion over 1 to 2 hours once 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

- Cycle 8, 10, 12, & 14: 100 mg/m

#### Supportive therapy, IE portion

- Mesna (Mesnex) as follows:
- Cycle 8, 10, 12, & 14: 1080 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Ifosfamide (Ifex) m
^{2}

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Ifosfamide (Ifex) m

- Cycle 8, 10, 12, & 14: 1080 mg/m
- Filgrastim (Neupogen) as follows:
- Cycle 8, 10, 12, & 14: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6
- ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

- Cycle 8, 10, 12, & 14: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6

**14-day cycle**

#### Chemotherapy, VDC portion Regimen B_{1} (Surgery Only)

- Vincristine (Oncovin) as follows:
- Cycle 9: 2 mg/m
^{2}IV push once on day 1 (maximum dose of 2 mg)- 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

- Cycle 9: 2 mg/m
- Doxorubicin (Adriamycin) as follows:
- Cycle 9: 75 mg/m
^{2}IV infusion over 48 hours 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

- Cycle 9: 75 mg/m
- Cyclophosphamide (Cytoxan) as follows:
- Cycle 9: 1200 mg/m
^{2}IV over 1 hour on Days 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

- Cycle 9: 1200 mg/m

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

- Mesna (Mesnex) as follows:
- Cycle 9: 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m
^{2}

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m

- Cycle 9: 720 mg/m
- 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

- Cycle 9: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2

**14-day cycle**

#### Chemotherapy, VC portion Regimen B_{2} & B_{3} (Radiation w/ or w/o Surgery)

- Vincristine (Oncovin) as follows:
- Cycle 9: 2 mg/m
^{2}IV push once on day 1 (maximum dose of 2 mg)- 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

- Cycle 9: 2 mg/m
- Cyclophosphamide (Cytoxan) as follows:
- Cycle 9: 1200 mg/m
^{2}IV over 1 hour on Days 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

- Cycle 9: 1200 mg/m

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

- Mesna (Mesnex) as follows:
- Cycle 9: 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m
^{2}

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m

- Cycle 9: 720 mg/m
- 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

- Cycle 9: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2

**14-day cycle**

#### Chemotherapy, VC portion

- Vincristine (Oncovin) as follows:
- Cycle 11: 2 mg/m
^{2}IV push once on day 1 (maximum dose of 2 mg)- 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

- Cycle 11: 2 mg/m
- Cyclophosphamide (Cytoxan) as follows:
- Cycle 11: 1200 mg/m
^{2}IV over 1 hour on Days 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

- Cycle 11: 1200 mg/m

#### Supportive therapy, VC portion

- Mesna (Mesnex) as follows:
- Cycle 11: 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m
^{2}

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m

- Cycle 11: 720 mg/m
- 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

- Cycle 11: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2

**14-day cycle**

#### Chemotherapy, VC portion Regimen B_{1} (Surgery Only)

- Vincristine (Oncovin) as follows:
- Cycle 13: 2 mg/m
^{2}IV push once on day 1 (maximum dose of 2 mg)- 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

- Cycle 13: 2 mg/m
- Cyclophosphamide (Cytoxan) as follows:
- Cycle 13: 1200 mg/m
^{2}IV over 1 hour on Days 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

- Cycle 13: 1200 mg/m

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

- Mesna (Mesnex) as follows:
- Cycle 13: 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m
^{2}

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m

- Cycle 13: 720 mg/m
- 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

- Cycle 13: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2

**14-day cycle**

#### Chemotherapy, VDC portion Regimen B_{2} & B_{3} (Radiation w/ or w/o Surgery)

- Vincristine (Oncovin) as follows:
- Cycle 13: 2 mg/m
^{2}IV push once on day 1 (maximum dose of 2 mg)- 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

- Cycle 13: 2 mg/m
- Doxorubicin (Adriamycin) as follows:
- Cycle 13: 75 mg/m
^{2}IV infusion over 48 hours 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

- Cycle 13: 75 mg/m
- Cyclophosphamide (Cytoxan) as follows:
- Cycle 13: 1200 mg/m
^{2}IV over 1 hour on Days 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

- Cycle 13: 1200 mg/m

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

- Mesna (Mesnex) as follows:
- Cycle 13: 720 mg/m
^{2}IV continuous infusion on day 1- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m
^{2}

- NOTE: Protocol states that Mesna (Mesnex) should be dosed as AT LEAST 60% of Cyclophosphamide (Cytoxan) m

- Cycle 13: 720 mg/m
- 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

- Cycle 13: 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2

**14-day cycle**

### 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. link to original article link to PMC article PubMed NCT00006734