VDC/IE

Ewing sarcoma and primitive neuroectodermal tumor (PNET) — first-line treatment in combination with local therapy (surgery and/or radiation).

VDC/IE (alternating every 2–3 weeks):
VDC cycles: Vincristine 2 mg IV Day 1, Doxorubicin 75 mg/m² IV over 24–48 hours Day 1, Cyclophosphamide 1200 mg/m² IV Day 1.
IE cycles: Ifosfamide 1800 mg/m² IV Days 1–5 (with mesna uroprotection), Etoposide 100 mg/m² IV Days 1–5.
Total: 14 cycles over ~28 weeks (COG AEWS0031 regimen). G-CSF support required.

• Cardiotoxicity (Doxorubicin): Cumulative cardiomyopathy. Monitor LVEF.
• Myelosuppression: Severe neutropenia. All agents are myelosuppressive. G-CSF support standard.
• Hemorrhagic Cystitis (Ifosfamide/Cyclophosphamide): Mesna uroprotection required with ifosfamide. Vigorous hydration needed.
• Peripheral Neuropathy (Vincristine): Cumulative; severe cases may require dose reduction.
• Neurotoxicity (Ifosfamide): Ifosfamide encephalopathy may occur; managed with methylene blue.
• SIADH (Vincristine/Cyclophosphamide): Monitor sodium.
• Embryo-Fetal Toxicity: All agents are teratogenic.

Myelosuppression (95%), Nausea/Vomiting (80%), Alopecia (90%), Fatigue (75%), Mucositis (35%), Peripheral neuropathy (40%), Constipation (25%), Cardiotoxicity (10%)

Adverse reaction frequencies reflect combination regimen data. Consult individual prescribing information for complete details.

VDC/IE uses five agents across two alternating regimens: Vincristine inhibits microtubule polymerization, causing mitotic arrest. Doxorubicin intercalates DNA and inhibits topoisomerase II. Cyclophosphamide and Ifosfamide are alkylating agents that cross-link DNA. Etoposide inhibits topoisomerase II, causing strand breaks. Alternating non-cross-resistant regimens maximizes tumor kill and limits cumulative organ toxicity.

• COG AEWS0031 — Compressed VDC/IE (every 2 weeks with G-CSF) vs standard VDC/IE (every 3 weeks) in Ewing sarcoma. Phase III, n=568. Interval-compressed therapy improved EFS.
  🔬 NCT00004024 ↗📄 Primary Publication ↗