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High-Dose Treosulfan and Melphalan as Consolidation Therapy Versus Standard Therapy for High-Risk (Metastatic) Ewing Sarcoma
R. Koch, H. Gelderblom, L. Haveman, B. Brichard, H. Jürgens, S. Cyprova, H. van den Berg, W. Hassenpflug, A. Raciborska, T. Ek, D. Baumhoer, G. Egerer, HT. Eich, M. Renard, P. Hauser, S. Burdach, J. Bovee, F. Bonar, P. Reichardt, J. Kruseova, J....
Language English Country United States
Document type Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 2004 to 1 year ago
Open Access Digital Library
from 1999-01-01
PubMed
35427190
DOI
10.1200/jco.21.01942
Knihovny.cz E-resources
- MeSH
- Busulfan analogs & derivatives MeSH
- Cyclophosphamide MeSH
- Child MeSH
- Doxorubicin MeSH
- Etoposide MeSH
- Sarcoma, Ewing * drug therapy MeSH
- Consolidation Chemotherapy MeSH
- Humans MeSH
- Melphalan MeSH
- Adolescent MeSH
- Disease-Free Survival MeSH
- Prospective Studies MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects MeSH
- Vincristine MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
PURPOSE: Ewing 2008R3 was conducted in 12 countries and evaluated the effect of treosulfan and melphalan high-dose chemotherapy (TreoMel-HDT) followed by reinfusion of autologous hematopoietic stem cells on event-free survival (EFS) and overall survival in high-risk Ewing sarcoma (EWS). METHODS: Phase III, open-label, prospective, multicenter, randomized controlled clinical trial. Eligible patients had disseminated EWS with metastases to bone and/or other sites, excluding patients with only pulmonary metastases. Patients received six cycles of vincristine, ifosfamide, doxorubicin, and etoposide induction and eight cycles of vincristine, actinomycin D, and cyclophosphamide consolidation therapy. Patients were randomly assigned to receive additional TreoMel-HDT or no further treatment (control). The random assignment was stratified by number of bone metastases (1, 2-5, and > 5). The one-sided adaptive-inverse-normal-4-stage-design was changed after the first interim analysis via Müller-Schäfer method. RESULTS: Between 2009 and 2018, 109 patients were randomly assigned, and 55 received TreoMel-HDT. With a median follow-up of 3.3 years, there was no significant difference in EFS between TreoMel-HDT and control in the adaptive design (hazard ratio [HR] 0.85; 95% CI, 0.55 to 1.32, intention-to-treat). Three-year EFS was 20.9% (95% CI, 11.5 to 37.9) in TreoMel-HDT and 19.2% (95% CI, 10.8 to 34.4) in control patients. The results were similar in the per-protocol collective. Males treated with TreoMel-HDT had better EFS compared with controls: median 1.0 years (95% CI, 0.8 to 2.2) versus 0.6 years (95% CI, 0.5 to 0.9); P = .035; HR 0.52 (0.28 to 0.97). Patients age < 14 years benefited from TreoMel-HDT with a 3-years EFS of 39.3% (95% CI, 20.4 to 75.8%) versus 9% (95% CI, 2.4 to 34); P = .016; HR 0.40 (0.19 to 0.87). These effects were similar in the per-protocol collective. This observation is supported by comparable results from the nonrandomized trial EE99R3. CONCLUSION: In patients with very high-risk EWS, additional TreoMel-HDT was of no benefit for the entire cohort of patients. TreoMel-HDT may be of benefit for children age < 14 years.
2nd Department of Pediatrics Semmelweis University Budapest Hungary
British Columbia Cancer Research Centre Vancouver BC Canada
Centre for Clinical Trials Muenster University of Muenster Muenster Germany
Charles University Motol Children's Hospital Prague Czech Republic
Childhood Cancer Center Queen Silvia Children's Hospital Gothenburg Sweden
Chris O'Brien Lifehouse Camperdown Australia
Clinic of Orthopedics University Hospital Essen West German Cancer Centre Essen Germany
Department of Clinical Radiology Klinikum Ibbenbüren Ibbenbüren Germany
Department of Clinical Sciences Skåne University Hospital Lund Sweden
Department of Internal Medicine 5 Heidelberg University Hospital Heidelberg Germany
Department of Medical Oncology Chris O'Brien Lifehouse Sydney Australia
Department of Medical Oncology Leiden University Medical Center Leiden the Netherlands
Department of Medical Oncology Sarcoma Center University of Duisburg Essen Essen Germany
Department of Oncology and Hematology University Children's Hospital Basel Basel Switzerland
Department of Oncology and Palliative Care Helios Klinikum Berlin Buch Berlin Germany
Department of Orthopaedics Semmelweis University Budapest Hungary
Department of Pathology Leiden University Medical Center Leiden the Netherlands
Department of Pediatrics University Hospital Erlangen Erlangen Germany
Department of Radiation Oncology University Hospital Muenster Muenster Germany
Department of Solid Tumors Princess Máxima Center for Pediatric Oncology Utrecht the Netherlands
Department of Thoracic Surgery Ruhrlandklinik University Hospital Essen Essen Germany
Douglass Hanly Moir Pathology Macquarie Park Australia
Faculty of Medicine and Health University of Sydney Sydney Australia
German Consortium for Translational Cancer Research German Cancer Research Centre Essen Germany
Institute of Biostatistics and Clinical Research University of Muenster Muenster Germany
Institute of Clinical Medicine Vilnius University Vilnius Lithuania
Paediatrics 3 University Hospital Essen Essen Germany
Pediatric Hematology and Oncology University Hospital Eppendorf Hamburg Germany
Pediatric Hematology and Oncology University Hospital Leuven Gasthuisberg Leuven Belgium
Sydney Medical School University of Sydney Sydney Australia
West German Cancer Centre Network Essen and Muenster Germany
References provided by Crossref.org
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