TY - JOUR
T1 - High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases
T2 - Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008
AU - Dirksen, Uta
AU - Brennan, Bernadette
AU - Le Deley, Marie Cécile
AU - Cozic, Nathalie
AU - van den Berg, Henk
AU - Bhadri, Vivek
AU - Brichard, Bénédicte
AU - Claude, Line
AU - Craft, Alan
AU - Amler, Susanne
AU - Gaspar, Natalie
AU - Gelderblom, Hans
AU - Goldsby, Robert
AU - Gorlick, Richard
AU - Grier, Holcombe E.
AU - Guinbretiere, Jean Marc
AU - Hauser, Peter
AU - Hjorth, Lars
AU - Janeway, Katherine
AU - Juergens, Heribert
AU - Judson, Ian
AU - Krailo, Mark
AU - Kruseova, Jarmila
AU - Kuehne, Thomas
AU - Ladenstein, Ruth
AU - Lervat, Cyril
AU - Lessnick, Stephen L.
AU - Lewis, Ian
AU - Linassier, Claude
AU - Marec-Berard, Perrine
AU - Marina, Neyssa
AU - Morland, Bruce
AU - Pacquement, Hélène
AU - Paulussen, Michael
AU - Randall, R. Lor
AU - Ranft, Andreas
AU - Le Teuff, Gwénaël
AU - Wheatley, Keith
AU - Whelan, Jeremy
AU - Womer, Richard
AU - Oberlin, Odile
AU - Hawkins, Douglas S.
AU - Euro-E.W.I.N.G. 99 Investigators
AU - Ewing 2008 Investigators
PY - 2019
Y1 - 2019
N2 - PURPOSE: The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases. METHODS: From 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and P value were corrected for the three previous interim analyses by the inverse normal method. RESULTS: Of 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; P = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; P = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm. CONCLUSION: In ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.
AB - PURPOSE: The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases. METHODS: From 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and P value were corrected for the three previous interim analyses by the inverse normal method. RESULTS: Of 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; P = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; P = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm. CONCLUSION: In ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.
U2 - 10.1200/JCO.19.00915
DO - 10.1200/JCO.19.00915
M3 - Article
C2 - 31553693
AN - SCOPUS:85075814144
SN - 0732-183X
VL - 37
SP - 3192
EP - 3202
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 34
ER -