Emerging novel agents for patients with advanced Ewing sarcoma: a report from the Children’s Oncology Group (COG) New Agents for Ewing Sarcoma Task Force

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Ewing sarcoma is a small round blue cell malignancy arising from bone or soft tissue and most commonly affects adolescents and young adults. Metastatic and relapsed Ewing sarcoma have poor outcomes and recurrences remain common. Owing to the poor outcomes associated with advanced disease and the need for a clear research strategy, the Children’s Oncology Group Bone Tumor Committee formed the New Agents for Ewing Sarcoma Task Force to bring together experts in the field to evaluate and prioritize new agents for incorporation into clinical trials. This group’s mission was to evaluate scientific and clinical challenges in moving new agents forward and to recommend agents and trial designs to the Bone Tumor Committee. The task force generated a framework for vetting prospective agents that included critical evaluation of each drug by using both clinical and non-clinical parameters. Representative appraisal of agents of highest priority, including eribulin, dinutuximab, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, anti-angiogenic tyrosine kinase inhibitors, and poly-ADP-ribose polymerase (PARP) inhibitors, is described. The task force continues to analyze new compounds by using the paradigm established.

Related collections

Most cited references 92

Record: found
Abstract: found
Article: not found

Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: a report from the Children's Oncology Group.

Richard Womer, Daniel West, Mark Krailo … (2012)

Chemotherapy 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. This 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 750×10(6)/L and a platelet count greater than 75×10(9)/L. Patients received vincristine (2 mg/m2), doxorubicin (75 mg/m2), and cyclophosphamide (1.2 g/m2) alternating with ifosfamide (9 g/m2) and etoposide (500 mg/m2) 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). Five 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=.048). The toxicity of the regimens was similar. For localized Ewing sarcoma, chemotherapy administered every 2 weeks is more effective than chemotherapy administered every 3 weeks, with no increase in toxicity.

0 comments Cited 168 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Mesenchymal stem cell features of Ewing tumors.

Pierre Charbord, Karine Laud, Olivier Delattre … (2007)

The cellular origin of Ewing tumor (ET), a tumor of bone or soft tissues characterized by specific fusions between EWS and ETS genes, is highly debated. Through gene expression analysis comparing ETs with a variety of normal tissues, we show that the profiles of different EWS-FLI1-silenced Ewing cell lines converge toward that of mesenchymal stem cells (MSC). Moreover, upon EWS-FLI1 silencing, two different Ewing cell lines can differentiate along the adipogenic lineage when incubated in appropriate differentiation cocktails. In addition, Ewing cells can also differentiate along the osteogenic lineage upon long-term inhibition of EWS-FLI1. These in silico and experimental data strongly suggest that the inhibition of EWS-FLI1 may allow Ewing cells to recover the phenotype of their MSC progenitor.

0 comments Cited 159 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Primary disseminated multifocal Ewing sarcoma: results of the Euro-EWING 99 trial.

Uta Dirksen, Charlotte H. B. S. van den Berg, Alan W Craft … (2010)

To improve the poor prognosis of patients with primary disseminated multifocal Ewing sarcomas (PDMES) with a dose-intense treatment concept. From 1999 to 2005, 281 patients with PDMES were enrolled onto the Euro-EWING 99 R3 study. Median age was 16.2 years (range, 0.4 to 49 years). Recommended treatment consisted of six cycles of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE), one cycle of vincristine, dactinomycin, and ifosfamide (VAI), local treatment (surgery and/or radiotherapy), and high-dose busulfan-melphalan followed by autologous stem-cell transplantation (HDT/SCT). After a median follow-up of 3.8 years, event-free survival (EFS) and overall survival (OS) at 3 years for all 281 patients were 27% +/- 3% and 34% +/- 4% respectively. Six VIDE cycles were completed by 250 patients (89%); 169 patients (60%) received HDT/SCT. The estimated 3-year EFS from the start of HDT/SCT was 45% for 46 children younger than 14 years. Cox regression analyses demonstrated increased risk at diagnosis for patients older than 14 years (hazard ratio [HR] = 1.6), a primary tumor volume more than 200 mL (HR = 1.8), more than one bone metastatic site (HR = 2.0), bone marrow metastases (HR = 1.6), and additional lung metastases (HR = 1.5). An up-front risk score based on these HR factors identified three groups with EFS rates of 50% for score or= 5 (70 patients; P < .0001). PDMES patients may survive with intensive multimodal therapy. Age, tumor volume, and extent of metastatic spread are relevant risk factors. A score based on these factors may facilitate risk-adapted treatment approaches.

0 comments Cited 152 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Kelly Bailey: Role: ConceptualizationRole: MethodologyRole: VisualizationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing

ORCID: https://orcid.org/0000-0003-3925-3243

Carrye Cost: Role: ConceptualizationRole: MethodologyRole: VisualizationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing

Ian Davis: Role: MethodologyRole: Writing – Review & Editing

Julia Glade-Bender: Role: MethodologyRole: Writing – Review & Editing

Patrick Grohar: Role: MethodologyRole: Writing – Review & Editing

Peter Houghton: Role: MethodologyRole: Writing – Review & Editing

Michael Isakoff: Role: MethodologyRole: Writing – Review & Editing

Elizabeth Stewart: Role: MethodologyRole: Writing – Review & Editing

Nadia Laack: Role: MethodologyRole: Writing – Review & Editing

Jason Yustein: Role: MethodologyRole: Writing – Review & Editing

Damon Reed: Role: MethodologyRole: Writing – Review & Editing

Katherine Janeway: Role: Writing – Review & Editing

Richard Gorlick: Role: Writing – Review & Editing

Stephen Lessnick: Role: MethodologyRole: Project AdministrationRole: SupervisionRole: Writing – Review & Editing

Steven DuBois: Role: ConceptualizationRole: MethodologyRole: Project AdministrationRole: SupervisionRole: VisualizationRole: Writing – Review & Editing

Pooja Hingorani: Role: ConceptualizationRole: MethodologyRole: Project AdministrationRole: SupervisionRole: VisualizationRole: Writing – Review & Editing

Journal

Journal ID (nlm-ta): F1000Res

Journal ID (iso-abbrev): F1000Res

Journal ID (pmc): F1000Research

Title: F1000Research

Publisher: F1000 Research Limited (London, UK )

ISSN (Electronic): 2046-1402

Publication date (Electronic): 15 April 2019

Publication date Collection: 2019

Volume: 8

Electronic Location Identifier: F1000 Faculty Rev-493

Affiliations

[1 ]Division of Pediatric Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

[2 ]Center for Cancer and Blood Disorders, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA

[3 ]Departments of Pediatrics and Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA

[4 ]Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

[5 ]Departement of Pediatrics, Van Andel Institute, Helen De Vos Children’s Hospital and Michigan State University, Grand Rapids, MI, USA

[6 ]Greehey Children’s Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX, USA

[7 ]Center for Cancer and Blood Disorders, Connecticut Children’s Medical Center, Hartford, CT, USA

[8 ]Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

[9 ]Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA

[10 ]The Faris D. Virani Ewing Sarcoma Center at the Texas Children’s Cancer Center, Baylor College of Medicine, Houston, TX, USA

[11 ]AYA Program, Moffitt Cancer Center, Tampa, FL, USA

[12 ]Johns Hopkins All Children’s Hospital, St. Petersburg, FL, USA

[13 ]Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA, USA

[14 ]Division of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, TX, USA

[15 ]Center for Childhood Cancer and Blood Diseases, Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA

[16 ]Division of Pediatric Hematology/Oncology/Bone Marrow Transplantation, The Ohio State University College of Medicine, Columbus, OH, USA

[17 ]Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ, USA

Author notes

[a ] phingorani@ 123456phoenixchildrens.com

No competing interests were disclosed.

Author information

Kelly Bailey https://orcid.org/0000-0003-3925-3243

Article

DOI: 10.12688/f1000research.18139.1

PMC ID: 6468706

PubMed ID: 32742637

SO-VID: 9e0b5b12-e075-463a-8ba1-4eccaba610b3

License:

This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date accepted : 10 April 2019

Funding

Funded by: NCTN Operations Center Grant

Award ID: U10CA180886

This work is supported by the Children’s Oncology Group and the National Cancer Institute of the National Institutes of Health under NCTN Operations Center Grant U10CA180886.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Emerging novel agents for patients with advanced Ewing sarcoma: a report from the Children’s Oncology Group (COG) New Agents for Ewing Sarcoma Task Force

Read this article at

Abstract

Related collections

Drug Repurposing

Most cited references 92

Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: a report from the Children's Oncology Group.

Mesenchymal stem cell features of Ewing tumors.

Primary disseminated multifocal Ewing sarcoma: results of the Euro-EWING 99 trial.

Author and article information

Contributors

Journal

Affiliations

Author notes

Author information

Article

History

Funding

Categories

Comments

Comment on this article

Similar content 202

Cited by 25

Most referenced authors 1,927