{"entity":{"id":"siopel-3","kind":"trial","name":"SIOPEL-3","aka":["SIOPEL 3","SIOPEL3","SIOP-SIOPEL-3"],"tldr":"SIOPEL-3 showed that children with standard-risk hepatoblastoma can be cured with cisplatin alone before and after surgery, leaving out doxorubicin and its heart damage, because the cure rate was the same as with the two-drug combination.","summary":"SIOPEL-3 was the international liver tumour trial of the SIOP group. Children with standard-risk hepatoblastoma were randomised to cisplatin alone or to cisplatin plus doxorubicin, given as pre-operative chemotherapy with delayed resection and continued after surgery; the primary endpoint was the complete resection rate, with survival and toxicity as secondary endpoints. A separate high-risk stratum received intensified therapy.\n\nComplete resection was achieved in 95 percent of the cisplatin group and 93 percent of the combination group; three-year event-free survival was 83 against 85 percent and overall survival 95 against 93 percent, while grade 3 or 4 acute toxicity was far more frequent with the combination (74.4 against 20.6 percent). Cisplatin monotherapy with delayed resection is the standard for standard-risk hepatoblastoma on the corpus's hepatoblastoma page, with sodium thiosulfate added after each dose to protect hearing following SIOPEL-6.","status":"positive","asOf":"2026-09-22","links":[{"label":"ClinicalTrials.gov NCT00003912","url":"https://clinicaltrials.gov/study/NCT00003912"}],"tags":["soc-trials"],"related":[],"cancers":["hepatoblastoma","childhood-cancers"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["cisplatin","doxorubicin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-siopel-3-cisplatin-vs-plado-standard-risk-hepatoblastoma-perilongo-nejm-2009"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00003912","phase":"3","setting":"Standard-risk hepatoblastoma in children (tumour confined to the liver, no more than three sectors involved, no metastases): pre-operative cisplatin alone against cisplatin plus doxorubicin (PLADO), with delayed resection and post-operative chemotherapy","sponsor":"Societe Internationale d'Oncologie Pediatrique","result":"Complete resection 95 percent with cisplatin alone against 93 percent with cisplatin plus doxorubicin; three-year overall survival 95 against 93 percent; grade 3 or 4 toxicity 20.6 against 74.4 percent.","yearReported":2009,"enrolled":255,"enrolledBasis":"randomised","enrolledNote":"The registry gives an estimated 260 for the whole liver tumour programme; the standard-risk randomisation reported in the New England Journal of Medicine randomised 255 children (126 to cisplatin, 129 to cisplatin plus doxorubicin) between 1998 and 2006.","outcomes":[{"endpoint":"Complete resection (intention to treat)","primary":true,"unit":"%","arms":[{"name":"Cisplatin alone","n":126,"value":95},{"name":"Cisplatin + doxorubicin (PLADO)","n":129,"value":93}],"source":"https://doi.org/10.1056/NEJMoa0810613"},{"endpoint":"Event-free survival at 3 years","unit":"%","arms":[{"name":"Cisplatin alone","n":126,"value":83,"note":"95% CI 77 to 90; median follow-up 46 months"},{"name":"Cisplatin + doxorubicin (PLADO)","n":129,"value":85,"note":"95% CI 79 to 92"}],"source":"https://doi.org/10.1056/NEJMoa0810613"},{"endpoint":"Overall survival at 3 years","unit":"%","arms":[{"name":"Cisplatin alone","n":126,"value":95,"note":"95% CI 91 to 99"},{"name":"Cisplatin + doxorubicin (PLADO)","n":129,"value":93,"note":"95% CI 88 to 98"}],"source":"https://doi.org/10.1056/NEJMoa0810613"},{"endpoint":"Acute grade 3 or 4 adverse events","unit":"%","arms":[{"name":"Cisplatin alone","n":126,"value":20.6},{"name":"Cisplatin + doxorubicin (PLADO)","n":129,"value":74.4}],"source":"https://doi.org/10.1056/NEJMoa0810613"}]},"route":"/trials/siopel-3/","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":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"}],"paper":[{"id":"paper-siopel-3-cisplatin-vs-plado-standard-risk-hepatoblastoma-perilongo-nejm-2009","kind":"paper","name":"SIOPEL-3: cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma","route":"/key-papers/paper-siopel-3-cisplatin-vs-plado-standard-risk-hepatoblastoma-perilongo-nejm-2009/"}]}}