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Single Center Experience of a New Intensive Induction Therapy for Ewing’s Family of Tumors: Feasibility, Toxicity, and Stem Cell Mobilization Properties

From the Meyerstein Institute of Oncology, Middlesex Hospital, University College London Hospitals National Health Service Trust, London, United Kingdom; and Royal National Orthopaedic Hospital, Stanmore, London, United Kingdom.

Address reprint requests to J.S. Whelan, MD, Meyerstein Institute of Oncology, Middlesex Hospital, University College London Hospitals National Health Service Trust, Mortimer St, London W1T 3AA; email: jeremy.whelan{at}uclh.org.

Purpose: To examine the feasibility, tolerability, and toxicity of an intensified induction regimen (vincristine, ifosfamide, doxorubicin, and etoposide [VIDE]) in patients with newly diagnosed Ewing’s family of tumors (EFT); to assess ability to maintain dose-intensity, and predictability of peripheral-blood stem cell mobilization.

Patients and Methods: Thirty patients were treated with vincristine 1.4 mg/m² (maximum 2 mg) on day 1, doxorubicin 20 mg/m², ifosfamide 3 g/m² plus mesna and etoposide 150 mg/m² on days 1 to 3. Cycles were given every 21 days for up to six cycles.

Results: One-hundred and seventy cycles of VIDE were given. The median treatment interval was 21 days (21 to 42) and nadir count: hemoglobin 8.3 (6.3 to 11.9), neutrophils 0.045 (0.0 to 2.1), and platelets 45 (3 to 343). There were 96 episodes of infection requiring hospitalization (56%). Growth factor support reduced infectious complications by 34%. Etoposide dose was reduced, or omitted, in 24% of cycles. Four patients did not complete six cycles due to unacceptable toxicity and one patient progressed on treatment. Twenty patients underwent peripheral-blood stem cell harvesting, 15 after cycle 3, and five after cycle 4. Median CD34⁺ yield was 4.6 x 10⁶/kg per patient (1.8 to 14.5). Overall response to treatment, measured in 24 patients, was 88%. Seven of 11 patients undergoing surgery achieved greater than 90% necrosis of tumor (64%).

Conclusion: VIDE is an effective induction regimen with substantial but acceptable toxicity that allows predictable mobilization of stem cells. Maintenance of dose-intensity is feasible in the majority of patients. Growth factors play a role in maintaining dose-intensity and reduce infectious complications.

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