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Toxicity profile of delayed high dose sodium thiosulfate in children treated with carboplatin in conjunction with blood‐brain‐barrier disruption
Author(s) -
Neuwelt Edward A.,
GilmerKnight Kristin,
Lacy Cynthia,
Nicholson H. Stacy,
Kraemer Dale F.,
Doolittle Nancy D.,
Hornig Gregory W.,
Muldoon Leslie L.
Publication year - 2006
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.20529
Subject(s) - medicine , carboplatin , ototoxicity , sodium thiosulfate , nausea , vomiting , toxicity , chemotherapy , anesthesia , cisplatin , inorganic chemistry , chemistry
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 1 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 1 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. © 2005 Wiley‐Liss, Inc.