Journal Article Review Ahead of print
PubMed: 42561548 DOI: 10.1016/j.ctrv.2026.103196
Vinorelbine and low-dose cyclophosphamide as maintenance therapy in the treatment of Ewing sarcoma rationale for the international INTER-EWING-1 trial for Ewing sarcoma patients.
Cancer Treat Rev 149:103196
Authors: Lianne M Haveman, Lisa L Hjalgrim, Cristina Mata Fernández, Perrine Marec-Berard, Valerie Laurence, Johannes H M Merks, Claudia Valverde Morales, Pablo Berlanga, Nathalie Gaspar, Sandra J Strauss, Bernadette Brennan, Roberto Luksch
Affiliations
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
- Department of pediatric and adolescent medicine, University Hospital Copenhagen, Rigshospitalet, Copenhagen, Denmark.
- Pediatric and Adolescent Hemato-Oncology Unit. Gregorio Marañón University Hospital, Madrid, Spain.
- Paediatric Hematology and Oncology Institute (IHOPe), Hospices Civils de Lyon, Lyon, France.
- Adolescents and Young Adults Unit, Medical Oncology and SIREDO (Care, Innovation and Research for Children, Adolescents, and Young Adults with Cancer) Departments, Curie Institute, Paris, France.
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
- Medical Oncology department, Hospital Universitari Vall d'Hebrón/ Vall d'Hebrón Institute of Oncology, Barcelona, Spain.
- Département de cancéologie de l'enfant et l'adolescent, Gustave Roussy, Université Paris Saclay, Villejuif, France.
- Department of Oncology, University College London Hospital NHS Foundation Trust, London NW1 2BU, UK.
- Paediatric Oncology Unit, Royal Manchester Children's Hospital, Manchester, United Kingdom.
- Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Abstract
INTRODUCTION
Ewing sarcoma (ES) is a malignant bone tumor with high relapse rates, especially in multi-metastatic disease despite multimodal treatment. The role of maintenance therapy in ES remains undefined. We systematically reviewed clinical trial data to assess the feasibility and rationale for maintenance therapy in localized and metastatic disease, with the aim to help selecting drugs to introduce as maintenance therapy within the trial.
METHODS
A PubMed search identified studies evaluating maintenance or metronomic therapy in ES and other pediatric sarcomas published between January 1990 and January 2020. Inclusion of articles required clinical use of maintenance therapy in pediatric (Ewing) sarcoma; case reports, preclinical studies, reviews, and phase I trials were excluded. A second PubMed search (February 2020-June 2025) updated the evidence base. Data on study design, patient characteristics, treatment regimens, and outcomes were extracted.
RESULTS
Of 3040 records identified in the first search, 20 were included: 11 included ES patients, 9 in other pediatric sarcomas. The update yielded 9 additional studies (3 ES, 6 other sarcomas). Vinorelbine, alone or combined with low-dose cyclophosphamide, was most frequently investigated, mainly in heavily pretreated relapsed or refractory ES patients, showing modest clinical activity. Strongest evidence derived from rhabdomyosarcoma (RMS) patients, where the randomized EpSSG RMS 2005-trial demonstrated improved long-term survival with vinorelbine/cyclophosphamide maintenance.
CONCLUSION
Vinorelbine plus low-dose cyclophosphamide represent a rational backbone for ES maintenance therapy, supported by evidence in RMS and limited ES data. Ongoing international efforts will define their clinical role when given for 6 months. Future studies should eventually clarify optimal duration, alternative agents, and long-term safety.
MeSH
Sarcoma, Ewing, Cyclophosphamide, Multiple Chronic Conditions, Maintenance, Sarcoma, Vinorelbine, Therapeutics