# SIOPEL-4: dose-dense cisplatin-based chemotherapy and surgery for high-risk hepatoblastoma

Source: https://onco.cc/key-papers/paper-siopel-4-dose-dense-cisplatin-high-risk-hepatoblastoma-zsiros-lancet-oncol-2013/  
OnCo record `paper-siopel-4-dose-dense-cisplatin-high-risk-hepatoblastoma-zsiros-lancet-oncol-2013` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Weekly cisplatin with doxorubicin before surgery got almost every child with high-risk hepatoblastoma to respond and three quarters to complete removal of the tumour, with three-year survival of 83 percent in a group that previously did poorly.

## Summary

Prospective single-arm feasibility study of the SIOPEL group in 62 children with high-risk hepatoblastoma (39 with lung metastases): dose-dense cisplatin with doxorubicin before surgery (including transplantation and metastasectomy where needed), then carboplatin and doxorubicin.

60 of 61 evaluable patients had a partial response to pre-operative chemotherapy, 46 (74 percent) had complete resection and 49 (79 percent) were in complete remission at the end of therapy. Three-year event-free survival was 76 percent and overall survival 83 percent at a median follow-up of 52 months; 97 percent had grade 3 or 4 haematological toxicity and 71 percent febrile neutropenia.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Journal: The Lancet Oncology
- Year: 2013
- DOI: 10.1016/S1470-2045(13)70272-9
- Authors: Zsiros J, Brugieres L, Brock P, et al.
- Findings: Complete remission at the end of therapy 79 percent (95% CI 67 to 88).; Partial response to pre-operative chemotherapy in 98 percent; complete resection in 74 percent.; Three-year event-free survival 76 percent (65 to 87) and overall survival 83 percent (73 to 93).
- What it means: Dose-dense cisplatin became the SIOPEL standard for high-risk hepatoblastoma and one arm of the international PHITT trial.
- Caveats: Single-arm feasibility design with heavy haematological toxicity; hearing loss from cumulative cisplatin is a long-term concern.

## Sources

- Lancet Oncol 2013: https://doi.org/10.1016/S1470-2045(13)70272-9
- PubMed: https://pubmed.ncbi.nlm.nih.gov/23831416/

## Connected records

- cancers: [Hepatoblastoma](https://onco.cc/cancers/hepatoblastoma/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/)
- trials: [SIOPEL-4](https://onco.cc/trials/siopel-4/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)

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