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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

High-dose thiotepa-related neurotoxicity and the role of tramadol in children

Authors: Christophe Maritaz, Francois Lemare, Agnes Laplanche, Sylvie Demirdjian, Dominique Valteau-Couanet, Christelle Dufour

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Serious neurological adverse events (NAE) have occurred during treatment with high-dose thiotepa regimens of children with high-risk solid tumours. The objective was to assess the incidence of NAE related to high-dose thiotepa and to identify potential contributing factors that could exacerbate the occurrence of this neurotoxicity.

Methods

From May 1987 to March 2011, children with solid tumours treated with high-dose thiotepa were retrospectively identified. Each NAE detected led to an independent case analysis. Potential contributing factors were pre-specified and univariate/multivariable analyses were performed.

Results

Three hundred seven courses of thiotepa (251 patients) were identified. The total dose per treatment ranged from 600 to 900 mg/m2. 81 NAE (26%) were identified. 46 NAE were related to high-dose thiotepa during the first course (18.3%) and 11 during the second course (19.6%). The symptoms appeared in a median time of 2 days after the introduction of thiotepa. Central and peripheral symptoms were headaches, tremors, confusion, seizures, cerebellar syndrome, and coma. High-dose thiotepa was reintroduced in 18 cases and symptoms reappeared in 5 children. For 3 patients who had seizures during the first course, premedication with clonazepam for the second course has prevented recurrence of NAE. As contributing factors, brain tumour and tramadol treatment increased the risk of thiotepa-related neurotoxicity by 2 to 6 times respectively.

Conclusions

The incidence of neurotoxicity was 18.3%. Brain tumours and tramadol treatment are risk factors to consider when using high-dose thiotepa. The outcome of patients was favourable without sequelae in all cases and rechallenge with thiotepa was possible.
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Metadata
Title
High-dose thiotepa-related neurotoxicity and the role of tramadol in children
Authors
Christophe Maritaz
Francois Lemare
Agnes Laplanche
Sylvie Demirdjian
Dominique Valteau-Couanet
Christelle Dufour
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4090-6

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