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Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial
R. Koch, L. Haveman, R. Ladenstein, B. Brichard, H. Jürgens, S. Cyprova, H. van den Berg, W. Hassenpflug, A. Raciborska, T. Ek, D. Baumhoer, G. Egerer, L. Kager, M. Renard, P. Hauser, S. Burdach, JVMG. Bovee, AM. Hong, P. Reichardt, J. Kruseova,...
Jazyk angličtina Země Spojené státy americké
Typ dokumentu randomizované kontrolované studie, multicentrická studie, klinické zkoušky, fáze III, časopisecké články
Grantová podpora
108128
Deutsche Krebshilfe (German Cancer Aid)
10112018
Deutsche Krebshilfe (German Cancer Aid)
01GM0869
Bundesministerium für Bildung und Forschung (BMBF)
01KD2207A
Bundesministerium für Bildung und Forschung (BMBF)
01KT1310
Bundesministerium für Bildung und Forschung (BMBF)
Freely Accessible Science Journals od 1995
Open Access Digital Library od 1995-01-01
Open Access Digital Library od 1995-01-01
Odkazy
PubMed
37843857
DOI
10.1158/1078-0432.ccr-23-1966
Knihovny.cz E-zdroje
- MeSH
- doba přežití bez progrese choroby MeSH
- Ewingův sarkom * patologie MeSH
- kyselina zoledronová terapeutické užití MeSH
- lidé MeSH
- nádory kostí * patologie MeSH
- prospektivní studie MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
PURPOSE: The phase III, open-label, prospective, multicenter, randomized Ewing 2008R1 trial (EudraCT2008-003658-13) was conducted in 12 countries to evaluate the effect of zoledronic acid (ZOL) maintenance therapy compared with no add-on regarding event-free survival (EFS, primary endpoint) and overall survival (OS) in standard-risk Ewing sarcoma (EWS). PATIENTS AND METHODS: Eligible patients had localized EWS with either good histologic response to induction chemotherapy and/or small tumors (<200 mL). Patients received six cycles of VIDE induction and eight cycles of VAI (male) or eight cycles of VAC (female) consolidation. ZOL treatment started parallel to the sixth consolidation cycle. Randomization was stratified by tumor site (pelvis/other). The two-sided adaptive inverse-normal four-stage design (planned sample size 448 patients, significance level 5%, power 80%) was changed after the first interim analysis using the Müller-Schäfer method. RESULTS: Between April 2010 and November 2018, 284 patients were randomized (142 ZOL/142 no add-on). With a median follow-up of 3.9 years, EFS was not significantly different between ZOL and no add-on group in the adaptive design (HR, 0.74; 95% CI, 0.43-1.28, P = 0.27, intention-to-treat). Three-year EFS rates were 84.0% (95% CI, 77.7%-90.8%) for ZOL vs. 81.7% (95% CI, 75.2%-88.8%) for no add-on. Results were similar in the per-protocol collective. OS was not different between groups. The 3-year OS was 92.8% (95% CI, 88.4%-97.5%) for ZOL and 94.6% (95% CI, 90.9%-98.6%) for no add-on. Noticeable more renal, neurologic, and gastrointestinal toxicities were observed for ZOL (P < 0.05). Severe renal toxicities occurred more often in the ZOL arm (P = 0.003). CONCLUSIONS: In patients with standard-risk localized EWS, there is no additional benefit from maintenance treatment with ZOL.
2nd Dept of Pediatrics Semmelweis University Budapest Hungary
Central Clinical School Faculty of Medicine and Health The University of Sydney Sydney Australia
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
Comprehensive Cancer Center Erlangen EMN Erlangen Germany
Department of Clinical Radiology Klinikum Ibbenbüren Ibbenburen Germany
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 Orthopedic Oncology University Hospital Essen Essen Germany
Department of Paediatrics Medical University of Vienna Vienna Austria
Department of Pathology Leiden University Medical Center Leiden the Netherlands
Department of Pediatric Hematology and Oncology University Children's Hospital Muenster Germany
Department of Pediatrics University Hospital Erlangen Erlangen Germany
Department of Radiation Oncology Chris O'Brien Lifehouse Camperdown Australia
Department of Solid tumors Princess Máxima Center for Pediatric Oncology Utrecht the Netherlands
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 Germany
Institute of Clinical Medicine Vilnius University Vilnius Lithuania
Lund University Skane University Hospital Department of Clinical Sciences Lund Neurology Lund Sweden
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
St Anna Children's Hospital and Children's Cancer Research Institute
West German Cancer Centre Network Essen and Muenster Germany
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