High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases: Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008.
View/ Open
Date
2019-12ICR Author
Author
Dirksen, U
Brennan, B
Le Deley, M-C
Cozic, N
van den Berg, H
Bhadri, V
Brichard, B
Claude, L
Craft, A
Amler, S
Gaspar, N
Gelderblom, H
Goldsby, R
Gorlick, R
Grier, HE
Guinbretiere, J-M
Hauser, P
Hjorth, L
Janeway, K
Juergens, H
Judson, I
Krailo, M
Kruseova, J
Kuehne, T
Ladenstein, R
Lervat, C
Lessnick, SL
Lewis, I
Linassier, C
Marec-Berard, P
Marina, N
Morland, B
Pacquement, H
Paulussen, M
Randall, RL
Ranft, A
Le Teuff, G
Wheatley, K
Whelan, J
Womer, R
Oberlin, O
Hawkins, DS
Euro-E.W.I.N.G. 99 and Ewing 2008 Investigators
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Euro-E.W.I.N.G. 99 and Ewing 2008 Investigators
Humans
Bone Neoplasms
Lung Neoplasms
Neoplasm Recurrence, Local
Disease Progression
Antineoplastic Combined Chemotherapy Protocols
Neoadjuvant Therapy
Radiotherapy, Adjuvant
Pneumonectomy
Hematopoietic Stem Cell Transplantation
Transplantation, Autologous
Risk Assessment
Risk Factors
Time Factors
Adolescent
Adult
Middle Aged
Child
Child, Preschool
Infant
Europe
Female
Male
Young Adult
Sarcoma, Ewing
Progression-Free Survival
Research team
Sarcoma Clinical Trials
Language
eng
License start date
2019-12
Citation
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2019, 37 (34), pp. 3192 - 3202