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

Uta Dirksen, Bernadette Brennan, Marie Cécile Le Deley, Nathalie Cozic, Henk Van Den Berg, Vivek Bhadri, Bénédicte Brichard, Line Claude, Alan Craft, Susanne Amler, Natalie Gaspar, Hans Gelderblom, Robert Goldsby, Richard Gorlick, Holcombe E. Grier, Jean Marc Guinbretiere, Peter Hauser, Lars Hjorth, Katherine Janeway, Heribert JuergensIan Judson, Mark Krailo, Jarmila Kruseova, Thomas Kuehne, Ruth Ladenstein, Cyril Lervat, Stephen L. Lessnick, Ian Lewis, Claude Linassier, Perrine Marec-Berard, Neyssa Marina, Bruce Morland, Hélène Pacquement, Michael Paulussen, R. Lor Randall, Andreas Ranft, Gwénaël Le Teuff, Keith Wheatley, Jeremy Whelan, Richard Womer, Odile Oberlin, Douglas S. Hawkins

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3192-3202
Number of pages11
JournalJournal of Clinical Oncology
Volume37
Issue number34
DOIs
StatePublished - Jan 1 2019

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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, H. E., Guinbretiere, J. M., Hauser, P., Hjorth, L., Janeway, K., ... Hawkins, D. S. (2019). 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. Journal of Clinical Oncology, 37(34), 3192-3202. https://doi.org/10.1200/JCO.19.00915