Inclusion Criteria:

- Age greater than or equal to one year and less than or equal to 40 years at the time
of diagnosis

- Newly diagnosed, previously untreated patients with histologically or molecularly
confirmed Ewing sarcoma

- Adequate hematologic function:

- Absolute neutrophil count ≥ 1,000/μL

- Platelet count ≥ 100,000/μL

- Adequate renal function:

- Normal creatinine for age (See table below) OR

- Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 Age(Years) Maximum
Serum Creatinine (mg/dL) ≤ 5 0.8 6 to ≤ 10
1 11 to ≤ 15 1.2 ≥ 16 1.5

Adequate hepatic function:

- Total bilirubin ≤ 1.5 x the ULN for age

- AST ≤ 2.5 x the ULN for age [in the absence of hepatic involvement of tumor] Normal
cardiac function

- Shortening fraction greater than or equal to 28% by echocardiogram OR

- Left ventricular ejection fraction (LVEF) greater than or equal to 50% on technetium-
99m pertechnetate radionuclide cineangiography (MUGA) or echocardiogram

- Patients must consent to an indwelling central venous catheter.

- Sexually active patients of reproductive potential must be willing to use an
effective method of contraception.

Exclusion Criteria:

- Prior chemotherapy or radiotherapy (other than limited, emergent radiotherapy for
treatment of eg. spinal cord compromise or threatened airway)

- Pregnant or breastfeeding females