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High-dose chemother...
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Whelan, JeremyUniversity College London
(author)
High-dose chemotherapy and blood autologous stem-cell rescue compared with standard chemotherapy in localized high-risk ewing sarcoma : Results of Euro-E.W.I.N.G.99 and Ewing-2008
- Article/chapterEnglish2018
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LIBRIS-ID:oai:lup.lub.lu.se:0dc80c90-3f1f-4bd6-976c-001246b60220
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https://lup.lub.lu.se/record/0dc80c90-3f1f-4bd6-976c-001246b60220URI
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https://doi.org/10.1200/JCO.2018.78.2516DOI
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Language:English
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Summary in:English
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Purpose For over 30 years, the place of consolidation high-dose chemotherapy in Ewing sarcoma (ES) has been controversial. A randomized study was conducted to determine whether consolidation high-dose chemotherapy improved survival in patients with localized ES at high risk for relapse. Methods Randomization between busulfan and melphalan (BuMel) or standard chemotherapy (vincristine, dactinomycin, and ifosfamide [VAI], seven courses) was offered to patients if they were younger than 50 years of age with poor histologic response (≥ 10% viable cells) after receiving vincristine, ifosfamide, doxorubicin, and etoposide (six courses); or had a tumor volume at diagnosis >200 mL if unresected, or initially resected, or resected after radiotherapy. A 15% improvement in 3-year eventfree survival (EFS) was sought (hazard ratio [HR], 0.60). Results Between 2000 and 2015, 240 patients classified as high risk (median age, 17.1 years) were randomly assigned to VAI (n = 118) or BuMel (n = 122). Seventy-eight percent entered the trial because of poor histologic response after chemotherapy alone. Median follow-up was 7.8 years. In an intent-to-treat analysis, the risk of event was significantly decreased by BuMel comparedwith VAI: HR, 0.64 (95%CI, 0.43 to 0.95; P = .026); 3- and 8-year EFS were, respectively, 69.0%(95% CI, 60.2%to 76.6%) versus 56.7%(95%CI, 47.6%to 65.4%) and 60.7%(95%CI, 51.1%to 69.6%) versus 47.1%(95%CI, 37.7% to 56.8%). Overall survival (OS) also favored BuMel: HR, 0.63 (95% CI, 0.41 to 0.95; P = .028); 3- and 8-year OS were, respectively, 78.0% (95% CI, 69.6% to 84.5%) versus 72.2% (95% CI, 63.3% to 79.6%) and 64.5%(95%CI, 54.4% to 73.5%) versus 55.6%(95%CI, 45.8%to 65.1%). Results were consistent in the sensitivity analysis. Two patients died as a result of BuMel-related toxicity, one after standard chemotherapy. Significantly more BuMel patients experienced severe acute toxicities from this course of chemotherapy compared with multiple VAI courses. Conclusion BuMel improved EFS and OS when given after vincristine, ifosfamide, doxorubicin, and etoposide induction in localized ES with predefined high-risk factors. For this group of patients, BuMel may be an important addition to the standard of care.
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Le Deley, Marie CecileCentre Oscar Lambret
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Dirksen, UtaUniversity Hospital Essen
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Teuff, Gwénaël LeInstitut Gustave Roussy
(author)
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Brennan, BernadetteRoyal Manchester Children's Hospital
(author)
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Gaspar, NathalieInstitut Gustave Roussy
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Hawkins, Douglas S.Seattle Children’s Hospital
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Amler, SusanneUniversity of Münster
(author)
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Bauer, SebastianUniversity Hospital Essen
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Bielack, StefanKlinikum Stuttgart Olgahospital
(author)
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Blay, Jean YvesCentre Léon Bérard
(author)
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Burdach, StefanComprehensive Cancer Center München (CCC München)
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Castex, Marie PierreToulouse University Hospital
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Dilloo, DagmarUniversity Hospital Bonn
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Eggert, AngelikaCharité - University Medicine Berlin
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Gelderblom, HansLeiden University Medical Centre
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Gentet, Jean ClaudeLa Timone University Hospital
(author)
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Hartmann, WolfgangUniversity Hospital Münster
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Hassenpflug, Wolf AchimUniversity Medical Center Hamburg-Eppendorf
(author)
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Hjorth, LarsLund University,Lunds universitet,Skåne University Hospital(Swepub:lu)pedi-lhj
(author)
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Jimenez, MartaUNICANCER - Fédération des Centres de lutte contre le cancer
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Klingebiel, ThomasUniversity Hospital Frankfurt
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Kontny, UdoUniversitätsklinikum der RWTH Aachen
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Kruseova, JarmilaUniversity Hospital Motol
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Ladenstein, RuthSt. Anna Children's Hospital
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Laurence, ValerieCurie Institute, Paris
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Lervat, CyrilCentre Oscar Lambret
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Marec-Berard, PerrinePediatric Hematology and Oncology Institute (IHOPE)
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Marreaud, SandrineEuropean Organisation for Research and Treatment of Cancer
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Michon, JeanCurie Institute, Paris
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Morland, BruceBirmingham Children's Hospital
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Paulussen, MichaelChildren’s and Adolescents’ Hospital, Datteln
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Ranft, AndreasUniversity Hospital Essen
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Reichardt, PeterHELIOS Klinikum Berlin-Buch
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Van Den Berg, HendrikAcademic Medical Center of University of Amsterdam (AMC)
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Wheatley, KeithUniversity of Birmingham
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Judson, IanInstitute of Cancer Research London
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Lewis, IanNational Health Service Trust, NHS England
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Craft, AlanUniversity of Newcastle upon Tyne
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Juergens, HeribertUniversity Hospital Münster
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Oberlin, OdileInstitut Gustave Roussy
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University College LondonCentre Oscar Lambret
(creator_code:org_t)
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Euro-E.W.I.N.G.99
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EWING-2008
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In:Journal of Clinical Oncology36:31, s. 3110-31190732-183X
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Whelan, Jeremy
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Le Deley, Marie ...
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Dirksen, Uta
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Teuff, Gwénaël L ...
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Brennan, Bernade ...
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Gaspar, Nathalie
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Hawkins, Douglas ...
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Amler, Susanne
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Bauer, Sebastian
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Bielack, Stefan
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Blay, Jean Yves
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Burdach, Stefan
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Castex, Marie Pi ...
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Dilloo, Dagmar
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Eggert, Angelika
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Gelderblom, Hans
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Gentet, Jean Cla ...
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Hartmann, Wolfga ...
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Hassenpflug, Wol ...
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Hjorth, Lars
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Jimenez, Marta
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Klingebiel, Thom ...
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Kontny, Udo
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Kruseova, Jarmil ...
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Ladenstein, Ruth
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Laurence, Valeri ...
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Lervat, Cyril
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Marec-Berard, Pe ...
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Michon, Jean
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Morland, Bruce
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Paulussen, Micha ...
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Ranft, Andreas
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Reichardt, Peter
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Van Den Berg, He ...
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Wheatley, Keith
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Judson, Ian
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Lewis, Ian
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Craft, Alan
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Juergens, Heribe ...
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Oberlin, Odile
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