{"entity":{"id":"siopel-4","kind":"trial","name":"SIOPEL-4","aka":["SIOPEL 4","SIOPEL4","SIOP-SIOPEL-4"],"tldr":"SIOPEL-4 showed that giving cisplatin every week in a dense schedule, with doxorubicin, to children with high-risk hepatoblastoma got nearly all of them to respond and three quarters to complete resection, lifting three-year survival to 83 percent in a group that used to do poorly.","summary":"SIOPEL-4 was a prospective single-arm feasibility study of the SIOPEL group in 62 children with high-risk hepatoblastoma, 39 of them with lung metastases. Pre-operative treatment was dose-dense cisplatin (80 mg/m2 then 70 mg/m2 weekly) with doxorubicin over three cycles, followed by removal of all remaining tumour, including liver transplantation and metastasectomy where needed; patients still unresectable had further doxorubicin and carboplatin, and the rest received post-operative carboplatin and doxorubicin. The primary endpoint was complete remission at the end of treatment.\n\n60 of 61 evaluable patients responded to pre-operative chemotherapy, complete resection was achieved in 74 percent and 79 percent were in complete remission at the end of therapy; three-year event-free survival was 76 percent and overall survival 83 percent. Nearly every patient had grade 3 or 4 haematological toxicity and 71 percent had febrile neutropenia. Dose-dense cisplatin is the high-risk regimen on the corpus's hepatoblastoma page.","status":"positive","asOf":"2026-09-22","links":[{"label":"ClinicalTrials.gov NCT00077389","url":"https://clinicaltrials.gov/study/NCT00077389"}],"tags":["soc-trials"],"related":[],"cancers":["hepatoblastoma","childhood-cancers"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["cisplatin","doxorubicin","carboplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-siopel-4-dose-dense-cisplatin-high-risk-hepatoblastoma-zsiros-lancet-oncol-2013"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00077389","phase":"2","setting":"High-risk hepatoblastoma in children up to 18 (metastases, all liver sectors involved, extrahepatic abdominal disease, major vascular invasion, low alpha-fetoprotein or tumour rupture): dose-dense weekly cisplatin with doxorubicin before surgery, including liver transplantation and metastasectomy where needed, then carboplatin and doxorubicin after surgery","sponsor":"University of Leicester","result":"Complete remission at the end of therapy in 79 percent of 62 high-risk patients; complete resection 74 percent; three-year event-free survival 76 percent and overall survival 83 percent.","yearReported":2013,"enrolled":62,"enrolledBasis":"analysed","enrolledNote":"The registry gives an estimated 57 and was never updated; the Lancet Oncology report analysed 62 eligible patients enrolled between 2005 and 2009.","outcomes":[{"endpoint":"Complete remission at the end of treatment","primary":true,"unit":"%","arms":[{"name":"Dose-dense cisplatin with doxorubicin, surgery, then carboplatin and doxorubicin","n":62,"value":79,"note":"95% CI 67 to 88"}],"source":"https://doi.org/10.1016/S1470-2045(13)70272-9"},{"endpoint":"Partial response to pre-operative chemotherapy","unit":"%","arms":[{"name":"Dose-dense cisplatin with doxorubicin","n":61,"value":98,"note":"60 of 61 evaluable; 95% CI 91 to 100"}],"source":"https://doi.org/10.1016/S1470-2045(13)70272-9"},{"endpoint":"Complete resection of all tumour lesions","unit":"%","arms":[{"name":"Dose-dense cisplatin with doxorubicin, surgery","n":62,"value":74}],"source":"https://doi.org/10.1016/S1470-2045(13)70272-9"},{"endpoint":"Event-free survival at 3 years","unit":"%","arms":[{"name":"SIOPEL-4 regimen","n":62,"value":76,"note":"95% CI 65 to 87; median follow-up 52 months"}],"source":"https://doi.org/10.1016/S1470-2045(13)70272-9"},{"endpoint":"Overall survival at 3 years","unit":"%","arms":[{"name":"SIOPEL-4 regimen","n":62,"value":83,"note":"95% CI 73 to 93"}],"source":"https://doi.org/10.1016/S1470-2045(13)70272-9"},{"endpoint":"Febrile neutropenia (at least one episode)","unit":"%","arms":[{"name":"SIOPEL-4 regimen","n":62,"value":71}],"source":"https://doi.org/10.1016/S1470-2045(13)70272-9"}]},"route":"/trials/siopel-4/","neighbours":{"cancer":[{"id":"childhood-cancers","kind":"cancer","name":"Childhood cancers (all types)","route":"/cancers/childhood-cancers/"},{"id":"hepatoblastoma","kind":"cancer","name":"Hepatoblastoma","route":"/cancers/hepatoblastoma/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"}],"paper":[{"id":"paper-siopel-4-dose-dense-cisplatin-high-risk-hepatoblastoma-zsiros-lancet-oncol-2013","kind":"paper","name":"SIOPEL-4: dose-dense cisplatin-based chemotherapy and surgery for high-risk hepatoblastoma","route":"/key-papers/paper-siopel-4-dose-dense-cisplatin-high-risk-hepatoblastoma-zsiros-lancet-oncol-2013/"}]}}