{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T09:04:52Z","timestamp":1779786292832,"version":"3.53.1"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Etoposide is a key component of many frontline and salvage chemotherapy regimens in pediatric oncology. However, its clinical use may be complicated by acute hypersensitivity reactions, which can disrupt treatment continuity and compromise therapeutic efficacy. Recent pediatric studies indicate that the incidence of etoposide-associated hypersensitivity is higher than historically reported and varies according to disease type and administration conditions. This narrative review provides a comprehensive overview of etoposide hypersensitivity in children, integrating clinical, immunological, and pharmaceutical perspectives. Current evidence suggests that true IgE-mediated type I hypersensitivity is uncommon in pediatric patients, whereas most reactions are consistent with non-IgE-mediated mechanisms, often related to formulation excipients such as polysorbate 80 and ethanol. We discuss the clinical features and differential diagnosis of acute reactions associated with etoposide administration, including hypersensitivity reactions and infusion-related reactions, such as ethanol-related toxicity. In addition, modifiable risk factors, preventive measures, and management strategies\u2014such as infusion optimization, alternative formulations, and rapid desensitization protocols\u2014are critically reviewed. A mechanism-based approach to etoposide hypersensitivity is essential to ensure patient safety while maintaining treatment intensity in pediatric cancer care.<\/jats:p>","DOI":"10.3390\/cancers18071141","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T07:57:55Z","timestamp":1775116675000},"page":"1141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Etoposide Hypersensitivity Reactions in Pediatric Oncology: Understanding Mechanisms and Optimizing Management"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2900-9642","authenticated-orcid":false,"given":"Maria","family":"De Filippo","sequence":"first","affiliation":[{"name":"Pediatric Onco-Hematology Unit, Department of Maternal Infantile and Urological Sciences, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Zicari","sequence":"additional","affiliation":[{"name":"Allergy and Immunology Pediatric Unit, Department of Maternal Infantile and Urological Sciences, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1268-5038","authenticated-orcid":false,"given":"Bianca","family":"Cinicola","sequence":"additional","affiliation":[{"name":"Allergy and Immunology Pediatric Unit, Department of Maternal Infantile and Urological Sciences, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy"},{"name":"Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Capponi","sequence":"additional","affiliation":[{"name":"Pediatric Onco-Hematology Unit, Department of Maternal Infantile and Urological Sciences, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Granata","sequence":"additional","affiliation":[{"name":"Pediatric Onco-Hematology Unit, Department of Maternal Infantile and Urological Sciences, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Stefanachi","sequence":"additional","affiliation":[{"name":"Pediatric Onco-Hematology Unit, Department of Maternal Infantile and Urological Sciences, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Carosini","sequence":"additional","affiliation":[{"name":"Pharmacy Unit, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ferrozzi","sequence":"additional","affiliation":[{"name":"Pharmacy Unit, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1950-4754","authenticated-orcid":false,"given":"Loredana","family":"Amoroso","sequence":"additional","affiliation":[{"name":"Pediatric Onco-Hematology Unit, Department of Maternal Infantile and Urological Sciences, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1007\/s00228-013-1546-0","article-title":"Incidence, clinical features and management of hypersensitivity reactions to chemotherapeutic drugs in children with cancer","volume":"69","author":"Ruggiero","year":"2013","journal-title":"Eur. 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