Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group

Abstract

A B S T R A C T PurposeChemotherapy with alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide cycles and primary tumor treatment with surgery and/or radiation therapy constitute the usual approach to localized Ewing sarcoma in North America. We tested whether chemotherapy intensification through interval compression could improve outcome. Patients and MethodsThis was a prospective, randomized controlled trial for patients younger than 50 years old with newly diagnosed localized extradural Ewing sarcoma. Patients assigned to standard and intensified treatment were to begin chemotherapy cycles every 21 and 14 days, respectively, provided an absolute neutrophil count greater than 750 ϫ 10 6 /L and a platelet count greater than 75 ϫ 10 9 /L. Patients received vincristine (2 mg/m 2 ), doxorubicin (75 mg/m 2 ), and cyclophosphamide (1.2 g/m 2 ) alternating with ifosfamide (9 g/m 2 ) and etoposide (500 mg/m 2 ) for 14 cycles, with filgrastim (5 mg/kg per day; maximum, 300 mg) between cycles. Primary tumor treatment (surgery, radiation, or both) was to begin at week 13 (after four cycles in the standard arm and six cycles in the intensified arm). The primary end point was event-free survival (EFS). The study is registered at ClinicalTrials.gov (identifier: NCT00006734). ResultsFive hundred eighty-seven patients were enrolled and randomly assigned, and 568 patients were eligible, with 284 patients in each regimen. For all cycles, the median cycle interval for standard treatment was 21 days (mean, 22.45 days); for intensified treatment, the median interval was 15 days (mean, 17.29 days). EFS at a median of 5 years was 65% in the standard arm and 73% in the intensified arm (P ϭ .048). The toxicity of the regimens was similar. ConclusionFor localized Ewing sarcoma, chemotherapy administered every 2 weeks is more effective than chemotherapy administered every 3 weeks, with no increase in toxicity.

Adolescent and Young Adult Oncology, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology

“…18 Additionally, for Ewing sarcoma, outcomes are worse for patients ≥18 years of age compared with patients <18 years. [19][20][21] Conversely, 5-year relative survival is better in AYA patients with medulloblastomas and germ-cell tumors compared with in children with these tumors, possibly reflecting biologic differences in the tumors of each age group. Compared with adults 40 years and older, AYA patients tend to have better survival rates, except for those with breast and prostate cancer.…”

Oncogenic fusion protein EWS-FLI1 is a network hub that regulates alternative splicing

“…Patient's samples and informed consent were obtained from 43 German patients treated within the Euro-E.W.I.N.G.-99 (EE99) trial and from 14 German patients treated within the European Intergroup Cooperative Ewing Sarcoma Studies (EICESS)-92 trial (74,78). An additional 29 samples were from patients who participated in the referenced clinical trials and signed informed consent for inclusion of their tumor in biology investigations (79). All data and informatics for this publication were obtained with coded ESTS that had all identifying information removed.…”

Has the Level of Evidence of Podium Presentations at the Musculoskeletal Tumor Society Annual Meeting Changed Over Time?

“…In addition, with limited patient enrollment, statistically significant endpoints are difficult to obtain [6]. Despite these obstacles, multicenter (Children's Oncology Group) and international (European and American Osteosarcoma Study Group) pediatric and medical oncology collaborations have completed sarcoma RCTs, the results of which have improved clinical practice [5,47,48].…”

“…Despite this, other fields have overcome these obstacles to generate high-quality sarcoma-focused RCTs [32,47,48]. High-level orthopaedic oncology studies are necessary to advance clinical care.…”