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Sodium thiosulphate does not reduce cisplatin efficacy in standard-risk hepatoblastoma
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CHICAGO — The addition of sodium thiosulphate to cisplatin chemotherapy exhibited end-of-treatment anti-tumor efficacy without increasing adverse outcomes in pediatric patients with standard-risk hepatoblastoma, according to the results of the phase 3 SIOPEL 6 trial presented at the ASCO Annual Meeting.
Treatment with cisplatin can lead to lasting bilateral hearing loss. Sodium thiosulphate (Fennec Pharmaceuticals) may reduce this risk; however, it can also reduce the anti-tumor efficacy of cisplatin, according to study background.
“Children with hepatoblastoma go deaf on treatment, resulting in permanent hearing loss in over half of children treated for the disease,” Penelope R. Brock, MD, PhD, FRCPCH, consultant pediatric oncologist at the Great Ormond Street Hospital in London and international chair of SIOPEL, told HemOnc Today. “If you have a disease where over 95% [of patients] are going to be cured but over half of them are going to be deaf for the rest of their lives, you are going to want to try to prevent deafness.”
Brock and colleagues evaluated data from 113 pediatric patients (median age at diagnosis, 12.8 months) with newly diagnosed standard-risk hepatoblastoma. Researchers randomly assigned patients to receive biweekly cycles of 80 mg/m2 cisplatin alone (n = 53) or with 20 g/m2 sodium thiosulphate (n = 60). Patients received four treatment cycles prior to tumor resection and two treatment cycles following tumor resection.
Researchers used serum alpha-fetoprotein and liver imaging to assess progression following the second and fourth preoperative cycles. Patients assigned sodium thiosulphate who exhibited progression following the second cycle discontinued sodium thiosulphate and began receiving doxorubicin (60 mg/m2).
Hearing loss measured by pure tone audiometry at or after age 3.5 years served as the primary endpoint. Short-term anti-tumor efficacy — defined as disease status at the end of treatment, evaluated following every 20 patients — served as a secondary endpoint. The current analysis includes interim safety results.
Researchers evaluated data from 94 patients (n = 47 for each arm) after four preoperative cycles. A comparable proportion of patients in the cisplatin monotherapy arm and cisplatin plus sodium thiosulphate arm demonstrated partial response (86% vs. 90%), stable disease (8% vs. 5%) and progressive disease (6% vs. 5%).
Ninety-eight percent of patients who received cisplatin plus sodium thiosulphate following resection and postoperative chemotherapy experienced complete remission, compared with 92% of the cisplatin monotherapy arm.
Researchers observed similar tolerability and rates of acute toxicity between study arms. Two patient deaths occurred — both in the cisplatin monotherapy arm — and there were three cases of disease progression (cisplatin monotherapy, n = 2; cisplatin plus sodium thiosulphate, n = 1).
Researchers expect to report outcomes related to the primary endpoint in 2017.
“The preliminary data are showing that this treatment is safe for children [with hepatoblastoma],” Brock said. “We are delighted to be able to show that with this particular tumor and standard-risk disease, there is no difference in complete remission rate between children who received sodium thiosulphate and those who did not.” – by Cameron Kelsall
Reference:
Brock PR, et al. Abstract 10039. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.
For more information:
Penelope R. Brock, MD, PhD, FRCPCH, can be reached at Great Ormond Street Hospital, Great Ormond Street, London WC1N 3JH; e-mail: peppymeunier@gmail.com.
Disclosure: The study was funded by Fennec Pharmaceuticals. The researchers report no relevant financial disclosures.