SIOPEL 6, A Multicentre Open Label Randomised Phase III Trial of the Efficacy of Sodium Thiosulphate in Reducing Ototoxicity in Patients Receiving Cisplatin Chemotherapy for Standard Risk Hepatoblastoma.
SIOPEL 6 was conducted by The International Childhood Liver Tumour Strategy Group, SIOPEL, a group of medical specialists founded in 1987 under the umbrella of the International Society of Paediatric Oncology (SIOP). The study was initiated in October 2007 initially in the United Kingdom and completed enrollment at the end of 2014, 52 sites from 11 countries enrolled 109 evaluable patients. The SIOPEL trial was conducted in standard risk hepatoblastoma where the effectiveness of the platinum treatment is very high, and the trial is being carefully monitored to identify an excess treatment failure rate.
One hundred and nine randomised patients (52 Cis and 57 Cis+STS) are evaluable. The combination of Cis+STS was generally well tolerated. With a follow up of 52months, 3yr EFS is Cis 78.8% and Cis+STS 82.1% 3yr OS is Cis 92.3% and Cis+STS 98.2%. Treatment failure defined as PD at 4 cycles was equivalent in both arms. Among the first 99 evaluable patients, hearing loss occurred in 30/45=67.0% under Cis and in 20/54=37.0% under Cis+STS, corresponding to a relative risk of 0.56(P=0.0033).
This randomised phase III trial in SR-HB of cisplatin versus cisplatin plus sodium thiosulfate shows that the addition of sodium thiosulfate significantly reduces the incidence of cisplatin-induced hearing loss without any evidence of tumour protection.