Rhabdomyosarcoma, pediatric

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Intermediate Risk

COG ARST1431 Protocol A (VAC/VI Only)

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (COG ARST1431)	2016-2025	Phase 3 (C)	VAC/VI & Temsirolimus	TBD

Protocol, Cycles 1-4 (Weeks 1 through 12)

Chemotherapy

• Vincristine (Oncovin) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • 0.30 to 0.34 m²: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • 0.35 to 0.39 m²: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • 0.40 to 0.44 m²: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • 0.45 to 0.49 m²: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • 0.50 to 0.54 m²: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • 0.55 to 0.59 m²: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • 0.60 m² or more: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
• Dactinomycin (Cosmegen) by the following weight-based criteria:
  • 3.0 to 4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 4.6 to 6.0 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 6.1 to 7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 7.4 to 8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 8.7 to 9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 10.0 to 11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 11.3 to 12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 12.6 to 13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 14 kg or more: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
• Cyclophosphamide (Cytoxan) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 220 mg IV over 60 minutes on day 1 of weeks 1 and 7
  • 0.30 to 0.34 m²: 280 mg IV over 60 minutes on day 1 of weeks 1 and 7
  • 0.35 to 0.39 m²: 360 mg IV over 60 minutes on day 1 of weeks 1 and 7
  • 0.40 to 0.44 m²: 440 mg IV over 60 minutes on day 1 of weeks 1 and 7
  • 0.45 to 0.49 m²: 520 mg IV over 60 minutes on day 1 of weeks 1 and 7
  • 0.50 to 0.54 m²: 600 mg IV over 60 minutes on day 1 of weeks 1 and 7
  • 0.55 to 0.59 m²: 660 mg IV over 60 minutes on day 1 of weeks 1 and 7
  • 0.60 m² or more: 1200 mg/m² IV over 60 minutes on day 1 of weeks 1 and 7
• Irinotecan (Camptosar) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 8 mg IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10
  • 0.30 to 0.34 m²: 12 mg IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10
  • 0.35 to 0.39 m²: 15 mg IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10
  • 0.40 to 0.44 m²: 18 mg IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10
  • 0.45 to 0.49 m²: 22 mg IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10
  • 0.50 to 0.54 m²: 24 mg IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10
  • 0.55 to 0.59 m²: 28 mg IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10
  • 0.60 m² or more: 50 mg/m² IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10

Supportive therapy

• Mesna (Mesnex) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 176 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.30 to 0.34 m²: 224 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.35 to 0.39 m²: 288 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.40 to 0.44 m²: 352 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.45 to 0.49 m²: 416 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.50 to 0.54 m²: 480 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.55 to 0.59 m²: 528 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.60 m² or more: 960 mg/m² IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
    • Mesna (Mesnex) can also be given PO at twice the IV dose

Protocol, Cycles 5 to 10 (Weeks 13 through 30)

Chemotherapy

• Vincristine (Oncovin) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • 0.30 to 0.34 m²: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • 0.35 to 0.39 m²: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • 0.40 to 0.44 m²: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • 0.45 to 0.49 m²: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • 0.50 to 0.54 m²: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • 0.55 to 0.59 m²: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • 0.60 m² or more: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
• Dactinomycin (Cosmegen) by the following weight-based criteria:
  • 3.0 to 4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 4.6 to 6.0 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 6.1 to 7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 7.4 to 8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 8.7 to 9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 10.0 to 11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 11.3 to 12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 12.6 to 13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 14 kg or more: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
• Cyclophosphamide (Cytoxan) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 220 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
  • 0.30 to 0.34 m²: 280 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
  • 0.35 to 0.39 m²: 360 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
  • 0.40 to 0.44 m²: 440 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
  • 0.45 to 0.49 m²: 520 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
  • 0.50 to 0.54 m²: 600 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
  • 0.55 to 0.59 m²: 660 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
  • 0.60 m² or more: 1200 mg/m² IV over 60 minutes on day 1 of weeks 13, 22, 28
• Irinotecan (Camptosar) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 8 mg IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25
  • 0.30 to 0.34 m²: 12 mg IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25
  • 0.35 to 0.39 m²: 15 mg IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25
  • 0.40 to 0.44 m²: 18 mg IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25
  • 0.45 to 0.49 m²: 22 mg IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25
  • 0.50 to 0.54 m²: 24 mg IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25
  • 0.55 to 0.59 m²: 28 mg IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25
  • 0.60 m² or more: 50 mg/m² IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25

Supportive therapy

• Mesna (Mesnex) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 176 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.30 to 0.34 m²: 224 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.35 to 0.39 m²: 288 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.40 to 0.44 m²: 352 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.45 to 0.49 m²: 416 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.50 to 0.54 m²: 480 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.55 to 0.59 m²: 528 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.60 m² or more: 960 mg/m² IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
    • Mesna (Mesnex) can also be given PO at twice the IV dose

Protocol, Cycles 11-14 (Weeks 31 through 42)

Chemotherapy

• Vincristine (Oncovin) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • 0.30 to 0.34 m²: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • 0.35 to 0.39 m²: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • 0.40 to 0.44 m²: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • 0.45 to 0.49 m²: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • 0.50 to 0.54 m²: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • 0.55 to 0.59 m²: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • 0.60 m² or more: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
• Dactinomycin (Cosmegen) by the following weight-based criteria:
  • 3.0 to 4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 4.6 to 6.0 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 6.1 to 7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 7.4 to 8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 8.7 to 9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 10.0 to 11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 11.3 to 12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 12.6 to 13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 14 kg or more: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
• Cyclophosphamide (Cytoxan) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 220 mg IV over 60 minutes on day 1 of weeks 34, 40
  • 0.30 to 0.34 m²: 280 mg IV over 60 minutes on day 1 of weeks 34, 40
  • 0.35 to 0.39 m²: 360 mg IV over 60 minutes on day 1 of weeks 34, 40
  • 0.40 to 0.44 m²: 440 mg IV over 60 minutes on day 1 of weeks 34, 40
  • 0.45 to 0.49 m²: 520 mg IV over 60 minutes on day 1 of weeks 34, 40
  • 0.50 to 0.54 m²: 600 mg IV over 60 minutes on day 1 of weeks 34, 40
  • 0.55 to 0.59 m²: 660 mg IV over 60 minutes on day 1 of weeks 34, 40
  • 0.60 m² or more: 1200 mg/m² IV over 60 minutes on day 1 of weeks 34, 40
• Irinotecan (Camptosar) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 8 mg IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37
  • 0.30 to 0.34 m²: 12 mg IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37
  • 0.35 to 0.39 m²: 15 mg IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37
  • 0.40 to 0.44 m²: 18 mg IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37
  • 0.45 to 0.49 m²: 22 mg IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37
  • 0.50 to 0.54 m²: 24 mg IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37
  • 0.55 to 0.59 m²: 28 mg IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37
  • 0.60 m² or more: 50 mg/m² IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37

Supportive therapy

• Mesna (Mesnex) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 176 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.30 to 0.34 m²: 224 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.35 to 0.39 m²: 288 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.40 to 0.44 m²: 352 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.45 to 0.49 m²: 416 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.50 to 0.54 m²: 480 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.55 to 0.59 m²: 528 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.60 m² or more: 960 mg/m² IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
    • Mesna (Mesnex) can also be given PO at twice the IV dose

Protocol, Maintenance Cycles 1-6

Chemotherapy

• Vinorelbine (Navelbine) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 4 mg IV push over 6 to 10 minutes on days 1, 8, and 15
  • 0.30 to 0.34 m²: 6 mg IV push over 6 to 10 minutes on days 1, 8, and 15
  • 0.35 to 0.39 m²: 7.5 mg IV push over 6 to 10 minutes on days 1, 8, and 15
  • 0.40 to 0.44 m²: 9 mg IV push over 6 to 10 minutes on days 1, 8, and 15
  • 0.45 to 0.49 m²: 11 mg IV push over 6 to 10 minutes on days 1, 8, and 15
  • 0.50 to 0.54 m²: 12 mg IV push over 6 to 10 minutes on days 1, 8, and 15
  • 0.55 to 0.59 m²: 14 mg IV push over 6 to 10 minutes on days 1, 8, and 15
  • 0.60 m² or more: 25 mg/m² IV push over 6 to 10 minutes on days 1, 8, and 15
• Cyclophosphamide (Cytoxan) 25 mg/m² PO once per day on days 1 through 28
  • Dose rounded to the nearest 25 mg capsule

28-day cycle

References

1. COG ARST1431: [https://clinicaltrials.gov/study/NCT02567435 NCT02567435]

COG ARST1431 Protocol B (VAC/VI & Temsirolimus)

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (COG ARST1431)	2016-2025	Phase 3 (E-esc)	VAC/VI	TBD if superior EFS (primary endpoint)

Protocol, Cycles 1-4 (Weeks 1 through 12)

Chemotherapy

• Temsirolimus (Torisel) by the following weight-based criteria:
  • Less than 10 kg: 0.5 mg/kg IV over 30 to 60 minutes once weekly on day 1 of weeks 1 through 12
  • More than 10 kg: 15 mg/m² (maximum dose of 25 mg) IV on day 1 of weeks 1 through 12
• Vincristine (Oncovin) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • 0.30 to 0.34 m²: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • 0.35 to 0.39 m²: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • 0.40 to 0.44 m²: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • 0.45 to 0.49 m²: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • 0.50 to 0.54 m²: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • 0.55 to 0.59 m²: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • 0.60 m² or more: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
• Dactinomycin (Cosmegen) by the following weight-based criteria:
  • 3.0 to 4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 4.6 to 6.0 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 6.1 to 7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 7.4 to 8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 8.7 to 9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 10.0 to 11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 11.3 to 12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 12.6 to 13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • 14 kg or more: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
• Cyclophosphamide (Cytoxan) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 220 mg IV over 60 minutes on day 1 of weeks 1 and 7
  • 0.30 to 0.34 m²: 280 mg IV over 60 minutes on day 1 of weeks 1 and 7
  • 0.35 to 0.39 m²: 360 mg IV over 60 minutes on day 1 of weeks 1 and 7
  • 0.40 to 0.44 m²: 440 mg IV over 60 minutes on day 1 of weeks 1 and 7
  • 0.45 to 0.49 m²: 520 mg IV over 60 minutes on day 1 of weeks 1 and 7
  • 0.50 to 0.54 m²: 600 mg IV over 60 minutes on day 1 of weeks 1 and 7
  • 0.55 to 0.59 m²: 660 mg IV over 60 minutes on day 1 of weeks 1 and 7
  • 0.60 m² or more: 1200 mg/m² IV over 60 minutes on day 1 of weeks 1 and 7
• Irinotecan (Camptosar) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 8 mg IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10
  • 0.30 to 0.34 m²: 12 mg IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10
  • 0.35 to 0.39 m²: 15 mg IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10
  • 0.40 to 0.44 m²: 18 mg IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10
  • 0.45 to 0.49 m²: 22 mg IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10
  • 0.50 to 0.54 m²: 24 mg IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10
  • 0.55 to 0.59 m²: 28 mg IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10
  • 0.60 m² or more: 50 mg/m² IV over 90 minutes once per day on days 1 through 5 of weeks 4 and 10

Supportive therapy

• Mesna (Mesnex) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 176 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.30 to 0.34 m²: 224 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.35 to 0.39 m²: 288 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.40 to 0.44 m²: 352 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.45 to 0.49 m²: 416 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.50 to 0.54 m²: 480 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.55 to 0.59 m²: 528 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.60 m² or more: 960 mg/m² IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
    • Mesna (Mesnex) can also be given PO at twice the IV dose

Protocol, Cycles 5-10 (Weeks 13 through 30)

Chemotherapy

• Temsirolimus (Torisel) by the following weight-based criteria:
  • Less than 10 kg: 0.5 mg/kg IV over 30 to 60 minutes once weekly on day 1 of weeks 21 through 30
  • More than 10 kg: 15 mg/m² (maximum dose of 25 mg) IV on day 1 of weeks 21 through 30
• Vincristine (Oncovin) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • 0.30 to 0.34 m²: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • 0.35 to 0.39 m²: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • 0.40 to 0.44 m²: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • 0.45 to 0.49 m²: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • 0.50 to 0.54 m²: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • 0.55 to 0.59 m²: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • 0.60 m² or more: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
• Dactinomycin (Cosmegen) by the following weight-based criteria:
  • 3.0 to 4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 4.6 to 6.0 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 6.1 to 7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 7.4 to 8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 8.7 to 9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 10.0 to 11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 11.3 to 12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 12.6 to 13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • 14 kg or more: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28

Give week 13 dose of Dactinomycin (Cosmegen) before beginning radiation therapy

• Cyclophosphamide (Cytoxan) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 220 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
  • 0.30 to 0.34 m²: 280 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
  • 0.35 to 0.39 m²: 360 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
  • 0.40 to 0.44 m²: 440 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
  • 0.45 to 0.49 m²: 520 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
  • 0.50 to 0.54 m²: 600 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
  • 0.55 to 0.59 m²: 660 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
  • 0.60 m² or more: 1200 mg/m² IV over 60 minutes on day 1 of weeks 13, 22, 28
• Irinotecan (Camptosar) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 8 mg IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25
  • 0.30 to 0.34 m²: 12 mg IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25
  • 0.35 to 0.39 m²: 15 mg IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25
  • 0.40 to 0.44 m²: 18 mg IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25
  • 0.45 to 0.49 m²: 22 mg IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25
  • 0.50 to 0.54 m²: 24 mg IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25
  • 0.55 to 0.59 m²: 28 mg IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25
  • 0.60 m² or more: 50 mg/m² IV over 90 minutes once per day on days 1 through 5 of weeks 16, 19, 25

Supportive therapy

• Mesna (Mesnex) by the following BSA-based criteria:

Mesna (Mesnex) can also be given PO at twice the IV dose

• • 0.25 to 0.29 m²: 176 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.30 to 0.34 m²: 224 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.35 to 0.39 m²: 288 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.40 to 0.44 m²: 352 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.45 to 0.49 m²: 416 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.50 to 0.54 m²: 480 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.55 to 0.59 m²: 528 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.60 m² or more: 960 mg/m² IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion

Protocol, Cycles 11-14 (Weeks 31 through 42)

Chemotherapy

• Temsirolimus (Torisel) by the following weight-based criteria:
  • Less than 10 kg: 0.5 mg/kg IV over 30 to 60 minutes once weekly on day 1 of weeks 31 through 42
  • More than 10 kg: 15 mg/m² (maximum dose of 25 mg) IV on day 1 of weeks 31 through 42
• Vincristine (Oncovin) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • 0.30 to 0.34 m²: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • 0.35 to 0.39 m²: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • 0.40 to 0.44 m²: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • 0.45 to 0.49 m²: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • 0.50 to 0.54 m²: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • 0.55 to 0.59 m²: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • 0.60 m² or more: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
• Dactinomycin (Cosmegen) by the following weight-based criteria:
  • 3.0 to 4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 4.6 to 6.0 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 6.1 to 7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 7.4 to 8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 8.7 to 9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 10.0 to 11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 11.3 to 12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 12.6 to 13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • 14 kg or more: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
• Cyclophosphamide (Cytoxan) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 220 mg IV over 60 minutes on day 1 of weeks 34, 40
  • 0.30 to 0.34 m²: 280 mg IV over 60 minutes on day 1 of weeks 34, 40
  • 0.35 to 0.39 m²: 360 mg IV over 60 minutes on day 1 of weeks 34, 40
  • 0.40 to 0.44 m²: 440 mg IV over 60 minutes on day 1 of weeks 34, 40
  • 0.45 to 0.49 m²: 520 mg IV over 60 minutes on day 1 of weeks 34, 40
  • 0.50 to 0.54 m²: 600 mg IV over 60 minutes on day 1 of weeks 34, 40
  • 0.55 to 0.59 m²: 660 mg IV over 60 minutes on day 1 of weeks 34, 40
  • 0.60 m² or more: 1200 mg/m² IV over 60 minutes on day 1 of weeks 34, 40
• Irinotecan (Camptosar) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 8 mg IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37
  • 0.30 to 0.34 m²: 12 mg IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37
  • 0.35 to 0.39 m²: 15 mg IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37
  • 0.40 to 0.44 m²: 18 mg IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37
  • 0.45 to 0.49 m²: 22 mg IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37
  • 0.50 to 0.54 m²: 24 mg IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37
  • 0.55 to 0.59 m²: 28 mg IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37
  • 0.60 m² or more: 50 mg/m² IV over 90 minutes once per day on days 1 through 5 of weeks 31, 37

Supportive therapy

• Mesna (Mesnex) by the following BSA-based criteria:

Mesna (Mesnex) can also be given PO at twice the IV dose

• • 0.25 to 0.29 m²: 176 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.30 to 0.34 m²: 224 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.35 to 0.39 m²: 288 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.40 to 0.44 m²: 352 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.45 to 0.49 m²: 416 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.50 to 0.54 m²: 480 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.55 to 0.59 m²: 528 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.60 m² or more: 960 mg/m² IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion

Protocol, Maintenance Cycles 1-6

Chemotherapy

• Vinorelbine (Navelbine) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 4 mg IV push over 6 to 10 minutes on days 1, 8, and 15
  • 0.30 to 0.34 m²: 6 mg IV push over 6 to 10 minutes on days 1, 8, and 15
  • 0.35 to 0.39 m²: 7.5 mg IV push over 6 to 10 minutes on days 1, 8, and 15
  • 0.40 to 0.44 m²: 9 mg IV push over 6 to 10 minutes on days 1, 8, and 15
  • 0.45 to 0.49 m²: 11 mg IV push over 6 to 10 minutes on days 1, 8, and 15
  • 0.50 to 0.54 m²: 12 mg IV push over 6 to 10 minutes on days 1, 8, and 15
  • 0.55 to 0.59 m²: 14 mg IV push over 6 to 10 minutes on days 1, 8, and 15
  • 0.60 m² or more: 25 mg/m² IV push over 6 to 10 minutes on days 1, 8, and 15
• Cyclophosphamide (Cytoxan) 25 mg/m² PO once per day on days 1 through 28
  • Dose rounded to the nearest 25 mg capsule

28-day cycle

References

1. COG ARST1431: [https://clinicaltrials.gov/study/NCT02567435 NCT02567435]

COG ARST0531 VAC Arm

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Hawkins et al. 2018 (COG ARST0531)	2006-2012	Phase 3 (C)	VAC/VI	Did not meet primary endpoint of EFS

Protocol, Weeks 1-15

Chemotherapy, Week 1

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 1

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 2

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 3

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 4

• Radiation therapy begins
• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 4

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 5

• Radiation therapy continues
• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 6

• Radiation therapy continues
• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 7

• Radiation therapy continues
• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 7

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 8

• Radiation therapy continues
• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 9

• Radiation therapy final week
• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 10

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 10

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 11

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 12

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 13

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 13

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Evaluation occurs during week 15

Protocol, Weeks 16-30

Chemotherapy, Week 16

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 16

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 17 Off Chemo

Chemotherapy, Week 18 Off Chemo

Chemotherapy, Week 19

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 19

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 20

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 21

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 22

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 22

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 23

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 24

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 25

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 25

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 26 Off Chemo

Chemotherapy, Week 27 Off Chemo

Chemotherapy, Week 28

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 28

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Evaluation occurs during week 30

Protocol, Weeks 31-43

Chemotherapy, Week 31

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 31

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 32

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 33

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 34

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 34

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 35

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 36

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 37

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 37

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 38 Off Chemo

Chemotherapy, Week 39 Off Chemo

Chemotherapy, Week 40

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 40

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Evaluation occurs during week 43

References

1. COG ARST0531: Hawkins DS, Chi Y, Anderson JR, Tian J, Arndt CAS, Bomgaars L, Donaldson SS, Hayes-Jordan A, Mascarenhas L, McCarville MB, McCune JS, McCowage G, Million L, Morris CD, Parham DM, Rodeberg DA, Rudzinski ER, Shnorhavorian M, Spunt SL, Skapek SX, Teot LA, Wolden S, Yock TI, Meyer WH. Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and Cyclophosphamide Does Not Improve Outcome for Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2018 Sep;36(27):2770-2777. Epub 2018 Aug 9. link to original article link to PMC article PubMed NCT00354835

COG ARST0531 VAC/VI Arm

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Hawkins et al. 2018 (COG ARST0531)	2006-2012	Phase 3 (E-switch-ic)	VAC	Did not meet primary endpoint of EFS EFS48: 59% vs 63%

Protocol, Weeks 1-15

Chemotherapy, Week 1

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 1

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 2

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 3

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 4

• Radiation therapy begins
• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
    • Administer Vincristine (Oncovin) prior to irinotecan
• Irinotecan (Camptosar) 50 mg/m² (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5

Chemotherapy, Week 5

• Radiation therapy continues
• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 6

• Radiation therapy continues
• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 7

• Radiation therapy continues
• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
    • Administer Vincristine (Oncovin) prior to irinotecan
• Irinotecan (Camptosar) 50 mg/m² (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5

Chemotherapy, Week 8

• Radiation therapy continues
• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 9

• Radiation therapy final week
• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 10

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 10

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 11

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 12

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 13

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 13

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Evaluation occurs during week 15

Protocol, Weeks 16-30

Chemotherapy, Week 16

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
    • Administer Vincristine (Oncovin) prior to irinotecan
• Irinotecan (Camptosar) 50 mg/m² (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5

Chemotherapy, Week 17

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 18 Off Chemo

Chemotherapy, Week 19

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
    • Administer Vincristine (Oncovin) prior to irinotecan
• Irinotecan (Camptosar) 50 mg/m² (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5

Chemotherapy, Week 20

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 21 Off Chemo

Chemotherapy, Week 22

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 22

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 23

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 24

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 25

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
    • Administer Vincristine (Oncovin) prior to irinotecan
• Irinotecan (Camptosar) 50 mg/m² (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5

Chemotherapy, Week 26

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 27 Off Chemo

Chemotherapy, Week 28

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 28

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Evaluation occurs during week 30

Protocol, Weeks 31-43

Chemotherapy, Week 31

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
    • Administer Vincristine (Oncovin) prior to irinotecan
• Irinotecan (Camptosar) 50 mg/m² (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5

Chemotherapy, Week 32

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 33

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 34

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 34

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 35 Off Chemo

Chemotherapy, Week 36 Off Chemo

Chemotherapy, Week 37

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
    • Administer Vincristine (Oncovin) prior to irinotecan
• Irinotecan (Camptosar) 50 mg/m² (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5

Chemotherapy, Week 38

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 39 Off Chemo

Chemotherapy, Week 40

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 40

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Evaluation occurs during week 43

References

1. COG ARST0531: Hawkins DS, Chi Y, Anderson JR, Tian J, Arndt CAS, Bomgaars L, Donaldson SS, Hayes-Jordan A, Mascarenhas L, McCarville MB, McCune JS, McCowage G, Million L, Morris CD, Parham DM, Rodeberg DA, Rudzinski ER, Shnorhavorian M, Spunt SL, Skapek SX, Teot LA, Wolden S, Yock TI, Meyer WH. Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and Cyclophosphamide Does Not Improve Outcome for Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2018 Sep;36(27):2770-2777. Epub 2018 Aug 9. link to original article link to PMC article PubMed NCT00354835

Low Risk

COG ARST1431 Protocol C (VAC/VA)

Study	Dates of enrollment	Evidence
Awaiting publication (COG ARST1431)	2016-2025	Non-randomized arm of phase 3 RCT

Protocol, Cycles 1-4 (Weeks 1 through 12)

Chemotherapy

• Vincristine (Oncovin) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
  • 0.30 to 0.34 m²: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
  • 0.35 to 0.39 m²: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
  • 0.40 to 0.44 m²: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
  • 0.45 to 0.49 m²: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
  • 0.50 to 0.54 m²: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
  • 0.55 to 0.59 m²: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
  • 0.60 m² or more: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
• Dactinomycin (Cosmegen) by the following weight-based criteria:
  • 3.0 to 4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
  • 4.6 to 6.0 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
  • 6.1 to 7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
  • 7.4 to 8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
  • 8.7 to 9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
  • 10.0 to 11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
  • 11.3 to 12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
  • 12.6 to 13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
  • 14 kg or more: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
• Cyclophosphamide (Cytoxan) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 220 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
  • 0.30 to 0.34 m²: 280 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
  • 0.35 to 0.39 m²: 360 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
  • 0.40 to 0.44 m²: 440 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
  • 0.45 to 0.49 m²: 520 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
  • 0.50 to 0.54 m²: 600 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
  • 0.55 to 0.59 m²: 660 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
  • 0.60 m² or more: 1200 mg/m² IV over 60 minutes on day 1 of weeks 1, 4, 7, 10

Supportive therapy

• Mesna (Mesnex) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 176 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.30 to 0.34 m²: 224 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.35 to 0.39 m²: 288 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.40 to 0.44 m²: 352 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.45 to 0.49 m²: 416 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.50 to 0.54 m²: 480 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.55 to 0.59 m²: 528 mg IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
  • 0.60 m² or more: 960 mg/m² IV over 15 to 30 minutes immediately prior to cyclophosphamide infusion, and again 4 and 8 hours after the start of cyclophosphamide infusion
    • Mesna (Mesnex) can also be given PO at twice the IV dose

Protocol, Cycles 5-8 (Weeks 13 through 24)

Chemotherapy

• Vincristine (Oncovin) by the following BSA-based criteria:
  • 0.25 to 0.29 m²: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
  • 0.30 to 0.34 m²: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
  • 0.35 to 0.39 m²: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
  • 0.40 to 0.44 m²: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
  • 0.45 to 0.49 m²: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
  • 0.50 to 0.54 m²: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
  • 0.55 to 0.59 m²: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
  • 0.60 m² or more: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
• Dactinomycin (Cosmegen) by the following weight-based criteria:
  • 3.0 to 4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
  • 4.6 to 6.0 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
  • 6.1 to 7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
  • 7.4 to 8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
  • 8.7 to 9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
  • 10.0 to 11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
  • 11.3 to 12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
  • 12.6 to 13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
  • 14 kg or more: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22

References

1. COG ARST1431: [https://clinicaltrials.gov/study/NCT02567435 NCT02567435]

COG ARST0331 protocol

In process

References

1. COG ARST0331: NCT00075582

High Risk

COG ARST0431 protocol

Study	Dates of enrollment	Evidence
Weigel et al. 2015 (COG ARST0431)	2006-07-17 to 2008-06-13	Non-randomized

Protocol, Weeks 1-6

Chemotherapy, Week 1 (IRIN-VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
    • Administer Vincristine (Oncovin) prior to irinotecan
• Irinotecan (Camptosar) 50 mg/m² (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5

Chemotherapy, Week 2 (VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 3 (VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 4 (IRIN-VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
    • Administer Vincristine (Oncovin) prior to irinotecan
• Irinotecan (Camptosar) 50 mg/m² (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5

Chemotherapy, Week 5 (VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Evaluation occurs in week 6, followed by:

Protocol, Weeks 7-19

Chemotherapy, Week 7 (VDC)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Doxorubicin (Adriamycin) by the following age-based criteria:
  • 1 year old or older: 37.5 mg/m² (Total dose per week of 75 mg/m²) IV over 24 hours once per day on days 1 through 2
  • Younger than 1 year old: 18.75 mg/m² IV over 24 hours once per day on days 1 through 2
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 7

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 8 (VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 9 (IE)

• Ifosfamide (Ifex) by the following age-based criteria:
  • 1 year old or older: 1800 mg/m² IV over 1 hour once per day on days 1 through 5
  • Younger than 1 year old: 900 mg/m² IV over 1 hour once per day on days 1 through 5
• Etoposide (Vepesid) by the following age-based criteria:
  • 1 year old or older: 100 mg/m² IV over 30 to 60 minutes once per day on days 1 through 5
  • Younger than 1 year old: 50 mg/m² IV over 30 to 60 minutes once per day on days 1 through 5

Supportive therapy, Week 9

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 360 mg/m² at hour 0, 4, and 8 from the start of each ifosfamide infusion on days 1 through 5
  • Younger than 3 years old: 180 mg/m² at hour 0, 4, and 8 from the start of each ifosfamide infusion on days 1 through 5

Chemotherapy, Week 10 Off Chemo

Chemotherapy, Week 11 (VDC)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Doxorubicin (Adriamycin) by the following age-based criteria:
  • 1 year old or older: 37.5 mg/m² (Total dose per week of 75 mg/m²) IV over 24 hours once per day on days 1 through 2
  • Younger than 1 year old: 18.75 mg/m² IV over 24 hours once per day on days 1 through 2
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 11

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 12 (VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 13 (IE)

• Ifosfamide (Ifex) by the following age-based criteria:
  • 1 year old or older: 1800 mg/m² IV over 1 hour once per day on days 1 through 5
  • Younger than 1 year old: 900 mg/m² IV over 1 hour once per day on days 1 through 5
• Etoposide (Vepesid) by the following age-based criteria:
  • 1 year old or older: 100 mg/m² IV over 30 to 60 minutes once per day on days 1 through 5
  • Younger than 1 year old: 50 mg/m² IV over 30 to 60 minutes once per day on days 1 through 5

Supportive therapy, Week 13

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 360 mg/m² at hour 0, 4, and 8 from the start of each ifosfamide infusion on days 1 through 5
  • Younger than 3 years old: 180 mg/m² at hour 0, 4, and 8 from the start of each ifosfamide infusion on days 1 through 5

Chemotherapy, Week 14 Off Chemo

Chemotherapy, Week 15 (VDC)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Doxorubicin (Adriamycin) by the following age-based criteria:
  • 1 year old or older: 37.5 mg/m² (Total dose per week of 75 mg/m²) IV over 24 hours once per day on days 1 through 2
  • Younger than 1 year old: 18.75 mg/m² IV over 24 hours once per day on days 1 through 2
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 15

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 16 (VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 17 (IE)

• Ifosfamide (Ifex) by the following age-based criteria:
  • 1 year old or older: 1800 mg/m² IV over 1 hour once per day on days 1 through 5
  • Younger than 1 year old: 900 mg/m² IV over 1 hour once per day on days 1 through 5
• Etoposide (Vepesid) by the following age-based criteria:
  • 1 year old or older: 100 mg/m² IV over 30 to 60 minutes once per day on days 1 through 5
  • Younger than 1 year old: 50 mg/m² IV over 30 to 60 minutes once per day on days 1 through 5

Supportive therapy, Week 17

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 360 mg/m² at hour 0, 4, and 8 from the start of each ifosfamide infusion on days 1 through 5
  • Younger than 3 years old: 180 mg/m² at hour 0, 4, and 8 from the start of each ifosfamide infusion on days 1 through 5

Evaluation occurs during week 19, followed by:

Protocol, Weeks 20-34

Chemotherapy, Week 20 (IRIN-VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
    • Administer Vincristine (Oncovin) prior to irinotecan
• Irinotecan (Camptosar) 50 mg/m² (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5

Chemotherapy, Week 21 (VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 22 (VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 23 (IRIN-VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
    • Administer Vincristine (Oncovin) prior to irinotecan
• Irinotecan (Camptosar) 50 mg/m² (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5

Chemotherapy, Week 24 (VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 25 Off Chemo

Chemotherapy, Week 26 (IE)

• Ifosfamide (Ifex) by the following age-based criteria:
  • 1 year old or older: 1800 mg/m² IV over 1 hour once per day on days 1 through 5
  • Younger than 1 year old: 900 mg/m² IV over 1 hour once per day on days 1 through 5
• Etoposide (Vepesid) by the following age-based criteria:
  • 1 year old or older: 100 mg/m² IV over 30 to 60 minutes once per day on days 1 through 5
  • Younger than 1 year old: 50 mg/m² IV over 30 to 60 minutes once per day on days 1 through 5

Supportive therapy, Week 26

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 360 mg/m² at hour 0, 4, and 8 from the start of each ifosfamide infusion on days 1 through 5
  • Younger than 3 years old: 180 mg/m² at hour 0, 4, and 8 from the start of each ifosfamide infusion on days 1 through 5

Chemotherapy, Week 27 Off Chemo

Chemotherapy, Week 28 (VDC)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Doxorubicin (Adriamycin) by the following age-based criteria:
  • 1 year old or older: 37.5 mg/m² (Total dose per week of 75 mg/m²) IV over 24 hours once per day on days 1 through 2
  • Younger than 1 year old: 18.75 mg/m² IV over 24 hours once per day on days 1 through 2
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 28

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 29 (VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 30 (IE)

• Ifosfamide (Ifex) by the following age-based criteria:
  • 1 year old or older: 1800 mg/m² IV over 1 hour once per day on days 1 through 5
  • Younger than 1 year old: 900 mg/m² IV over 1 hour once per day on days 1 through 5
• Etoposide (Vepesid) by the following age-based criteria:
  • 1 year old or older: 100 mg/m² IV over 30 to 60 minutes once per day on days 1 through 5
  • Younger than 1 year old: 50 mg/m² IV over 30 to 60 minutes once per day on days 1 through 5

Supportive therapy, Week 30

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 360 mg/m² at hour 0, 4, and 8 from the start of each ifosfamide infusion on days 1 through 5
  • Younger than 3 years old: 180 mg/m² at hour 0, 4, and 8 from the start of each ifosfamide infusion on days 1 through 5

Chemotherapy, Week 31 Off Chemo

Chemotherapy, Week 32 (VDC)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Doxorubicin (Adriamycin) by the following age-based criteria:
  • 1 year old or older: 37.5 mg/m² (Total dose per week of 75 mg/m²) IV over 24 hours once per day on days 1 through 2
  • Younger than 1 year old: 18.75 mg/m² IV over 24 hours once per day on days 1 through 2
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 32

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 33 (VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Evaluation occurs during week 34, followed by:

Protocol, Weeks 35-54

Chemotherapy, Week 35 (VAC)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 35

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 36 Off Chemo

Chemotherapy, Week 37 Off Chemo

Chemotherapy, Week 38 (VAC)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 38

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 39 Off Chemo

Chemotherapy, Week 40 Off Chemo

Chemotherapy, Week 41 (VAC)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 41

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 42 (VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 43 (VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 44 (VAC)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
• Dactinomycin (Cosmegen) by the following age-based criteria:
  • 1 year old or older: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
  • Younger than 1 year old: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
• Cyclophosphamide (Cytoxan) by the following age-based criteria:
  • 3 years old or older: 1200 mg/m² IV over 1 hour once per day on day 1
  • Younger than 3 years old: 40 mg/kg IV over 1 hour once per day on day 1

Supportive therapy, Week 44

• Mesna (Mesnex) by the following age-based criteria:
  • 3 years old or older: 240 mg/m² at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1
  • Younger than 3 years old: 8 mg/kg at hour 0, 4, and 8 from the start of each cyclophosphamide infusion on days 1

Chemotherapy, Week 45 Off Chemo

Chemotherapy, Week 46 Off Chemo

Chemotherapy, Week 47 (IRIN-VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
    • Administer Vincristine (Oncovin) prior to irinotecan
• Irinotecan (Camptosar) 50 mg/m² (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5

Chemotherapy, Week 48 (VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 49 Off Chemo

Chemotherapy, Week 50 (IRIN-VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1
    • Administer Vincristine (Oncovin) prior to irinotecan
• Irinotecan (Camptosar) 50 mg/m² (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5

Chemotherapy, Week 51 (VCR)

• Vincristine (Oncovin) by the following age-based criteria:
  • 3 years old or older: 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • 1 up to 3 years old: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
  • Younger than 1 year old: 0.025 mg/kg IV push over 1 minute once on day 1

Evaluation occurs during week 54

References

1. COG ARST0431: Weigel BJ, Lyden E, Anderson JR, Meyer WH, Parham DM, Rodeberg DA, Michalski JM, Hawkins DS, Arndt CAS. Intensive Multiagent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide and Vincristine/Doxorubicin/Cyclophosphamide, Irinotecan, and Radiation, in Patients with High-Risk Rhabdomyosarcoma: A Report from the Children's Oncology Group. J Clin Oncol. 2016 Oct;34(2):117-122. Epub 2015 Oct 26. link to original article link to PMC article PubMed NCT00354744