http://www.jco.org/cgi/content/abstract/24/24/3997
Impact of High-Dose Busulfan Plus Melphalan As Consolidation in
Metastatic Ewing Tumors: A Study by the Société Française des Cancers
de l'Enfant
Journal of Clinical Oncology, Vol 24, No 24 (August 20), 2006: pp.
3997-4002
© 2006 American Society of Clinical Oncology
DOI: 10.1200/JCO.2006.05.7059
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@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.