Dose-Intensified Compared With Standard Chemotherapy for Nonmetastatic Ewing Sarcoma Family of Tumors: A Children's Oncology Group Study

Abstract

A B S T R A C T PurposeThe 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. MethodsPatients 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. ResultsFour 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 ϭ .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. ConclusionDose escalation of alkylating agents as tested in this trial did not improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue.

Survival outcome among patients with Ewing’s sarcoma of bones and joints: a population-based cohort study

“…Oberlin et al 26 asserted that it was recommendable that smaller and more peripheral tumors should be dealt with through surgical resection, while larger and more central unresectable entities should be managed with radiotherapy. On the other hand, Granowetter et al 27 pointed out that radiotherapy was not appropriate for patients in whom there was no proof of microscopic remainders of malignant tissue after they underwent operations.…”

Treatment and Outcomes of Ewing Sarcoma in Turkish Adults: A Single Centre Experience

“…The National Cancer Institute's ES chemotherapy protocol was applied to both non-metastatic and metastatic patients (Table 2) (Granowetter et al, 2009). After every 3 cycles of chemotherapy, all patients were assessed with a physical examination of the thorax, abdomen, and extremities, and, if necessary, imaging and echocardiography were performed due to cardiotoxicity of antracyclin.…”

NCCN Guidelines Insights: Bone Cancer, Version 2.2017

“…39 Various dosage paradigms of VAC-IE (vincristine, doxorubicin, and cyclophosphamide, alternating with ifosfamide and etoposide) have been investigated. Although dose escalation of alkylating agents in VAC-IE did not improve outcomes for patients with localized disease, 40 chemotherapy intensification through interval compression has been shown to improve outcomes. The current standard of care for multiagent chemotherapy in the United States was established through Children's Oncology Group (COG) protocol AEWS0031 (ClinicalTrials.gov identifier: NCT00006734), which examined interval-compressed versus standard administration of VAC-IE for newly diagnosed, localized Ewing sarcoma.…”