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Impact of High-Dose Busulfan Plus Melphalan As Consolidation in Metastatic Ewing Tumors: A Study by the Société Française des Cancers de l'Enfant

Odile Oberlin, Annie Rey, Anne Sophie Desfachelles, Thierry Philip, Dominique Plantaz, Claudine Schmitt, Emmanuel Plouvier, Odile Lejars, Hervé Rubie, Philippe Terrier, Jean Michon

From the Departments of Paediatric Oncology, Biostatistics, and Pathology, Institut Gustave Roussy, Villejuif; Department of Paediatric Oncology, Centre Oscar Lambret, Lille; Department of Paediatric Oncology, Centre Léon Bérard, Lyon, France; Department of Paediatric Oncology, Hôpital Michalon, Grenoble; Department of Paediatric Oncology, Hôpital d'enfants, Nancy; Department of Paediatric Oncology, Centre hospitalo-universitaire, Besançon; Department of Paediatric Oncology, Hôpital Clocheville, Tours; Department of Paediatric Oncology, Hôpital Purpan, Toulouse; and the Department of Paediatric Oncology, Institut Curie, Paris, France

Address reprint requests to Odile Oberlin, MD, Department of Paediatric Oncology, Institut Gustave-Roussy, Rue Camille Desmoulins, 94805 Villejuif Cedex, France; e-mail: oberlin{at}igr.fr

PURPOSE: To improve the prognosis for patients with metastatic Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) using conventional chemotherapy and consolidation high-dose chemotherapy (HDCT) containing busulfan and melphalan.

PATIENTS AND METHODS: Ninety-seven unselected patients with newly diagnosed metastatic ES/PNET received induction chemotherapy that included five cycles of cyclophosphamide 150 mg/m²/d for 7 days, doxorubicin 35 mg/m²/d once, followed by two cycles of ifosfamide 1.8 g/m²/d for 5 days, and etoposide 100 mg/m²/d for 5 days. Patients in complete or very good partial remission received HDCT with busulfan total dose 600 mg/m² and melphalan 140 mg/m² followed by autologous blood stem cells. Local therapy (surgery and/or radiation therapy) was performed before or after HDCT.

RESULTS: Ninety-seven patients were enrolled from 1991 to 1999 (median age, 12.3 years; range, 0.2 to 25 years). Among them, 75 received HDCT. The 5-year event-free survival (EFS) rate for all 97 patients was 37% and the overall survival (OS) rate was 38%. The EFS after HDCT was 47%. The EFS for the 44 patients with lung-only metastases was 52%, whereas it was 36% for patients with bone metastases without bone marrow involvement. Among the 23 patients with bone marrow metastases, only one survived. The multivariate analysis for both EFS and for OS identified three independent prognostic factors: age, fever at diagnosis, and bone marrow involvement.

CONCLUSION: Compared with conventional chemotherapy, HDCT may yield benefits for patients with lung-only metastases or bone metastases. These results warrant confirmation in a randomized trial and provide part of the background data for the ongoing Euro-Ewing study.

Supported by Institut Gustave Roussy and by Société Française des Cancers de l'Enfant.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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