Toxicity profile of delayed high dose sodium thiosulfate in children treated with carboplatin in conjunction with blood-brain-barrier disruption

Purpose. To assess the safety of delayed high dose intravenous (i.v.) sodium thiosulfate (STS) in a case series of 12 children with malignant brain tumors who were treated with intraarterial (i.a.) carboplatin in conjunction with blood-brain-barrier disruption (BBBD). Methods. Twelve children ages 17 months-12 years underwent a total of 132 BBBD chemotherapy treatments and also received delayed high dose STS (i.v.). Dose I of STS (10-16 g/m(2)) was administered 2 or 4 hr after carboplatin, and a second STS dose was administered 4 hr after dose I if the child had impaired baseline hearing. Toxicity data were graded in accordance with the National Cancer Institute Common Toxicity Criteria (Version 2). Audiologic monitoring to evaluate the otoprotective potential of STS was performed on 11 children. Ototoxicity was defined in accordance with the American Speech-Language-Hearing Association (ASHA) criteria. Baseline and end of treatment hearing status were graded using Brock's criteria. Results. Nausea and vomiting were well controlled with anti-emetics administered approximately 30 min prior to STS infusion. Analogous to results in adult patients, there was mild transient hypernatremia and a trend for improved protection from ototoxicity in children who received STS delayed to 4 hr post-treatment versus 2 hr. Tumor responses were seen in heavily pre-treated patients with relatively chemo-resistant tumors, suggesting that STS did not protect the tumor from platinum cytotoxicity. Conclusion. High dose STS is well tolerated in children under 12 years of age. Further studies of STS in children are warranted to assess otoprotection and the impact of STS on platinum mediated efficacy.