SIOPEL 6: A multicenter open-label randomized phase III trial of the efficacy of sodium thiosulphate (STS) in reducing ototoxicity in patients receiving cisplatin (Cis) monotherapy for standard-risk hepatoblastoma (SR-HB).

TPS10094 Background: The SIOPEL 3 trial of Cis monotherapy and surgery in SR-HB showed a 3yr OS of 95% at 5 years. SR-HB is defined as tumor extension limited to PRETEXT I, II or III, no involvement of portal or hepatic veins, no intra-abdominal extrahepatic disease, AFP >100ng/ml and no metastases. At commonly used doses and schedules, Cis can cause permanent bilateral high-frequency hearing loss. Several pre-clinical and clinical studies in adults and children (particularly from the Oregon group) suggest that STS may reduce the risk of ototoxicity. There are however concerns that STS could reduce the anti-tumor efficacy of Cis, hence the time separation of Cis and STS and the close monitoring of the trial. Methods: Newly diagnosed patients with SR-HB are treated with 4 chemotherapy courses every 2 weeks before surgery and 2 courses after surgery. Patients are randomly assigned to receive Cis alone or Cis followed by STS. Cis 80mg/m2 is administered i.v. over 6 hrs. STS is administered i.v. exactly 6 hrs...