Dose-intensified compared with standard chemotherapy for nonmetastatic ewing sarcoma family of tumors: A children's oncology group study

Linda Granowetter, Richard Womer, Meenakshi Devidas, Mark Krailo, Chenguang Wang, Mark Bernstein, Neyssa Marina, Patrick Leavey, Mark Gebhardt, John Healey, Robert Cooper Shamberger, Allen Goorin, James Miser, James Meyer, Carola A.S. Arndt, Scott Sailer, Karen Marcus, Elizabeth Perlman, Paul Dickman, Holcombe E. Grier

Research output: Contribution to journalArticle

184 Citations (Scopus)

Abstract

Purpose: The Ewing sarcoma family of tumors (ESFT) is a group of malignant tumors of soft tissue and bone sharing a chromosomal translocation affecting the EWS locus. The Intergroup INT-0091 demonstrated the superiority of a regimen of vincristine, cyclophosphamide, doxorubicin (VDC), and dactinomycin alternating with ifosfamide and etoposide (IE) over VDC for patients with nonmetastatic ESFT of bone. The goal of this study was to determine whether a dose-intensified regimen of VDC alternating with IE would further improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue. Methods: Patients with previously untreated, nonmetastatic ESFT of bone or soft tissue were eligible. They were randomly assigned to receive standard doses of VDC/IE over 48 weeks or a dose-intensified regimen of VDC/IE over 30 weeks. Results: Four hundred seventy-eight patients met eligibility requirements: 231 patients received the standard regimen; 247 patients received the intensified regimen. The 5-year event-free survival (EFS) and overall survival rates for all eligible patients were 71.1% (95% CI, 67.7% to 75.0%) and 78.6% (95% CI, 74.6% to 82.1%), respectively. There was no significant difference (P = .57) in EFS between patients treated with the standard (5-year EFS, 72.1%; 95% CI, 65.8% to 77.5%) or intensified regimen (5-year EFS, 70.1%; 63.9% to 75%). Patients with soft tissue tumors accounted for 20% of the study population; there was no difference in outcome between patients with soft tissue and bone primary sites. Conclusion: Dose escalation of alkylating agents as tested in this trial did not improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue.

Original languageEnglish (US)
Pages (from-to)2536-2541
Number of pages6
JournalJournal of Clinical Oncology
Volume27
Issue number15
DOIs
StatePublished - May 20 2009

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Ewing's Sarcoma
Drug Therapy
Vincristine
Ifosfamide
Doxorubicin
Cyclophosphamide
Neoplasms
Etoposide
Bone and Bones
Disease-Free Survival
Genetic Translocation
Alkylating Agents
Dactinomycin
Survival Rate

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Dose-intensified compared with standard chemotherapy for nonmetastatic ewing sarcoma family of tumors : A children's oncology group study. / Granowetter, Linda; Womer, Richard; Devidas, Meenakshi; Krailo, Mark; Wang, Chenguang; Bernstein, Mark; Marina, Neyssa; Leavey, Patrick; Gebhardt, Mark; Healey, John; Shamberger, Robert Cooper; Goorin, Allen; Miser, James; Meyer, James; Arndt, Carola A.S.; Sailer, Scott; Marcus, Karen; Perlman, Elizabeth; Dickman, Paul; Grier, Holcombe E.

In: Journal of Clinical Oncology, Vol. 27, No. 15, 20.05.2009, p. 2536-2541.

Research output: Contribution to journalArticle

Granowetter, L, Womer, R, Devidas, M, Krailo, M, Wang, C, Bernstein, M, Marina, N, Leavey, P, Gebhardt, M, Healey, J, Shamberger, RC, Goorin, A, Miser, J, Meyer, J, Arndt, CAS, Sailer, S, Marcus, K, Perlman, E, Dickman, P & Grier, HE 2009, 'Dose-intensified compared with standard chemotherapy for nonmetastatic ewing sarcoma family of tumors: A children's oncology group study', Journal of Clinical Oncology, vol. 27, no. 15, pp. 2536-2541. https://doi.org/10.1200/JCO.2008.19.1478
Granowetter, Linda ; Womer, Richard ; Devidas, Meenakshi ; Krailo, Mark ; Wang, Chenguang ; Bernstein, Mark ; Marina, Neyssa ; Leavey, Patrick ; Gebhardt, Mark ; Healey, John ; Shamberger, Robert Cooper ; Goorin, Allen ; Miser, James ; Meyer, James ; Arndt, Carola A.S. ; Sailer, Scott ; Marcus, Karen ; Perlman, Elizabeth ; Dickman, Paul ; Grier, Holcombe E. / Dose-intensified compared with standard chemotherapy for nonmetastatic ewing sarcoma family of tumors : A children's oncology group study. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 15. pp. 2536-2541.
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abstract = "Purpose: The Ewing sarcoma family of tumors (ESFT) is a group of malignant tumors of soft tissue and bone sharing a chromosomal translocation affecting the EWS locus. The Intergroup INT-0091 demonstrated the superiority of a regimen of vincristine, cyclophosphamide, doxorubicin (VDC), and dactinomycin alternating with ifosfamide and etoposide (IE) over VDC for patients with nonmetastatic ESFT of bone. The goal of this study was to determine whether a dose-intensified regimen of VDC alternating with IE would further improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue. Methods: Patients with previously untreated, nonmetastatic ESFT of bone or soft tissue were eligible. They were randomly assigned to receive standard doses of VDC/IE over 48 weeks or a dose-intensified regimen of VDC/IE over 30 weeks. Results: Four hundred seventy-eight patients met eligibility requirements: 231 patients received the standard regimen; 247 patients received the intensified regimen. The 5-year event-free survival (EFS) and overall survival rates for all eligible patients were 71.1{\%} (95{\%} CI, 67.7{\%} to 75.0{\%}) and 78.6{\%} (95{\%} CI, 74.6{\%} to 82.1{\%}), respectively. There was no significant difference (P = .57) in EFS between patients treated with the standard (5-year EFS, 72.1{\%}; 95{\%} CI, 65.8{\%} to 77.5{\%}) or intensified regimen (5-year EFS, 70.1{\%}; 63.9{\%} to 75{\%}). Patients with soft tissue tumors accounted for 20{\%} of the study population; there was no difference in outcome between patients with soft tissue and bone primary sites. Conclusion: Dose escalation of alkylating agents as tested in this trial did not improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue.",
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T1 - Dose-intensified compared with standard chemotherapy for nonmetastatic ewing sarcoma family of tumors

T2 - A children's oncology group study

AU - Granowetter, Linda

AU - Womer, Richard

AU - Devidas, Meenakshi

AU - Krailo, Mark

AU - Wang, Chenguang

AU - Bernstein, Mark

AU - Marina, Neyssa

AU - Leavey, Patrick

AU - Gebhardt, Mark

AU - Healey, John

AU - Shamberger, Robert Cooper

AU - Goorin, Allen

AU - Miser, James

AU - Meyer, James

AU - Arndt, Carola A.S.

AU - Sailer, Scott

AU - Marcus, Karen

AU - Perlman, Elizabeth

AU - Dickman, Paul

AU - Grier, Holcombe E.

PY - 2009/5/20

Y1 - 2009/5/20

N2 - Purpose: The Ewing sarcoma family of tumors (ESFT) is a group of malignant tumors of soft tissue and bone sharing a chromosomal translocation affecting the EWS locus. The Intergroup INT-0091 demonstrated the superiority of a regimen of vincristine, cyclophosphamide, doxorubicin (VDC), and dactinomycin alternating with ifosfamide and etoposide (IE) over VDC for patients with nonmetastatic ESFT of bone. The goal of this study was to determine whether a dose-intensified regimen of VDC alternating with IE would further improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue. Methods: Patients with previously untreated, nonmetastatic ESFT of bone or soft tissue were eligible. They were randomly assigned to receive standard doses of VDC/IE over 48 weeks or a dose-intensified regimen of VDC/IE over 30 weeks. Results: Four hundred seventy-eight patients met eligibility requirements: 231 patients received the standard regimen; 247 patients received the intensified regimen. The 5-year event-free survival (EFS) and overall survival rates for all eligible patients were 71.1% (95% CI, 67.7% to 75.0%) and 78.6% (95% CI, 74.6% to 82.1%), respectively. There was no significant difference (P = .57) in EFS between patients treated with the standard (5-year EFS, 72.1%; 95% CI, 65.8% to 77.5%) or intensified regimen (5-year EFS, 70.1%; 63.9% to 75%). Patients with soft tissue tumors accounted for 20% of the study population; there was no difference in outcome between patients with soft tissue and bone primary sites. Conclusion: Dose escalation of alkylating agents as tested in this trial did not improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue.

AB - Purpose: The Ewing sarcoma family of tumors (ESFT) is a group of malignant tumors of soft tissue and bone sharing a chromosomal translocation affecting the EWS locus. The Intergroup INT-0091 demonstrated the superiority of a regimen of vincristine, cyclophosphamide, doxorubicin (VDC), and dactinomycin alternating with ifosfamide and etoposide (IE) over VDC for patients with nonmetastatic ESFT of bone. The goal of this study was to determine whether a dose-intensified regimen of VDC alternating with IE would further improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue. Methods: Patients with previously untreated, nonmetastatic ESFT of bone or soft tissue were eligible. They were randomly assigned to receive standard doses of VDC/IE over 48 weeks or a dose-intensified regimen of VDC/IE over 30 weeks. Results: Four hundred seventy-eight patients met eligibility requirements: 231 patients received the standard regimen; 247 patients received the intensified regimen. The 5-year event-free survival (EFS) and overall survival rates for all eligible patients were 71.1% (95% CI, 67.7% to 75.0%) and 78.6% (95% CI, 74.6% to 82.1%), respectively. There was no significant difference (P = .57) in EFS between patients treated with the standard (5-year EFS, 72.1%; 95% CI, 65.8% to 77.5%) or intensified regimen (5-year EFS, 70.1%; 63.9% to 75%). Patients with soft tissue tumors accounted for 20% of the study population; there was no difference in outcome between patients with soft tissue and bone primary sites. Conclusion: Dose escalation of alkylating agents as tested in this trial did not improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue.

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