TY - JOUR
T1 - High-dose chemotherapy and blood autologous stem-cell rescue compared with standard chemotherapy in localized high-risk ewing sarcoma
T2 - Results of Euro-E.W.I.N.G.99 and Ewing-2008
AU - Whelan, Jeremy
AU - Le Deley, Marie Cecile
AU - Dirksen, Uta
AU - Teuff, Gwénaël Le
AU - Brennan, Bernadette
AU - Gaspar, Nathalie
AU - Hawkins, Douglas S.
AU - Amler, Susanne
AU - Bauer, Sebastian
AU - Bielack, Stefan
AU - Blay, Jean Yves
AU - Burdach, Stefan
AU - Castex, Marie Pierre
AU - Dilloo, Dagmar
AU - Eggert, Angelika
AU - Gelderblom, Hans
AU - Gentet, Jean Claude
AU - Hartmann, Wolfgang
AU - Hassenpflug, Wolf Achim
AU - Hjorth, Lars
AU - Jimenez, Marta
AU - Klingebiel, Thomas
AU - Kontny, Udo
AU - Kruseova, Jarmila
AU - Ladenstein, Ruth
AU - Laurence, Valerie
AU - Lervat, Cyril
AU - Marec-Berard, Perrine
AU - Marreaud, Sandrine
AU - Michon, Jean
AU - Morland, Bruce
AU - Paulussen, Michael
AU - Ranft, Andreas
AU - Reichardt, Peter
AU - Van Den Berg, Hendrik
AU - Wheatley, Keith
AU - Judson, Ian
AU - Lewis, Ian
AU - Craft, Alan
AU - Juergens, Heribert
AU - Oberlin, Odile
N1 - Publisher Copyright:
© 2018 by American Society of Clinical Oncology.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85055841281&partnerID=8YFLogxK
U2 - 10.1200/JCO.2018.78.2516
DO - 10.1200/JCO.2018.78.2516
M3 - Article
AN - SCOPUS:85055841281
SN - 0732-183X
VL - 36
SP - 3110
EP - 3119
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 31
ER -
