TY - JOUR
T1 - Hydrocortisone to reduce dexamethasone-induced neurobehavioral side-effects in children with acute lymphoblastic leukaemia—results of a double-blind, randomised controlled trial with cross-over design
AU - van Hulst, Annelienke M.
AU - van den Akker, Erica L.T.
AU - Fiocco, Marta
AU - Verwaaijen, Emma J.
AU - Rensen, Niki
AU - van Litsenburg, Raphaële R.L.
AU - Pluijm, Saskia M.F.
AU - zwaan, c
AU - van Santen, Hanneke M.
AU - Pieters, Rob
AU - Evers, Andrea W.M.
AU - Grootenhuis, Martha A.
AU - van den Heuvel-Eibrink, Marry M.
N1 - Funding Information:
This study was funded by the non-profit organisation Kinderen Kankervrij ( KiKa ), project number 268 .
Publisher Copyright: © 2023 The Authors
PY - 2023/7
Y1 - 2023/7
N2 - Background: Dexamethasone is a cornerstone of paediatric acute lymphoblastic leukaemia (ALL) treatment, although it can induce serious side-effects. Our previous study suggests that children who suffer most from neurobehavioural side-effects might benefit from physiological hydrocortisone in addition to dexamethasone treatment. This study aimed to validate this finding. Methods: Our phase three, double-blind, randomised controlled trial with cross-over design included ALL patients (3–18 years) during medium-risk maintenance therapy in a national tertiary hospital between 17th May 2018 and 5th August 2020. A baseline measurement before and after a 5-day dexamethasone course was performed, whereafter 52 patients with clinically relevant neurobehavioural problems were randomised to receive an intervention during four subsequent dexamethasone courses. The intervention consisted of two courses hydrocortisone (physiological dose 10 mg/m2/d in circadian rhythm), followed by two courses placebo, or vice versa. Neurobehavioural problems were assessed before and after each course using the parent-reported Strengths and Difficulties Questionnaire (SDQ) as primary end-point. Secondary end-points were sleep problems, health-related quality of life (HRQoL), hunger feeling, and parental stress, measured with questionnaires and actigraphy. A generalised mixed model was estimated to study the intervention effect. Results: The median age was 5.5 years (range 3.0–18.8) and 61.5% were boys. The SDQ filled in by 51 primary caregivers showed no difference between hydrocortisone and placebo in reducing dexamethasone-induced neurobehavioral problems (estimated effect -2.05 (95% confidence interval (CI) -6.00–1.90). Also, no benefit from hydrocortisone compared to placebo was found for reducing sleep problems, hunger, parental stress or improving HRQoL. Conclusions: Hydrocortisone, when compared to placebo, had no additional effect in reducing clinically relevant dexamethasone-induced neurobehavioural problems. Therefore, hydrocortisone is not advised as standard of care for children with ALL who experience dexamethasone-induced neurobehavioural problems. Trial registration: Netherlands Trial Register NTR6695/NL6507 (https://trialsearch.who.int/) and EudraCT 2017–002738–22 (https://eudract.ema.europa.eu/).
AB - Background: Dexamethasone is a cornerstone of paediatric acute lymphoblastic leukaemia (ALL) treatment, although it can induce serious side-effects. Our previous study suggests that children who suffer most from neurobehavioural side-effects might benefit from physiological hydrocortisone in addition to dexamethasone treatment. This study aimed to validate this finding. Methods: Our phase three, double-blind, randomised controlled trial with cross-over design included ALL patients (3–18 years) during medium-risk maintenance therapy in a national tertiary hospital between 17th May 2018 and 5th August 2020. A baseline measurement before and after a 5-day dexamethasone course was performed, whereafter 52 patients with clinically relevant neurobehavioural problems were randomised to receive an intervention during four subsequent dexamethasone courses. The intervention consisted of two courses hydrocortisone (physiological dose 10 mg/m2/d in circadian rhythm), followed by two courses placebo, or vice versa. Neurobehavioural problems were assessed before and after each course using the parent-reported Strengths and Difficulties Questionnaire (SDQ) as primary end-point. Secondary end-points were sleep problems, health-related quality of life (HRQoL), hunger feeling, and parental stress, measured with questionnaires and actigraphy. A generalised mixed model was estimated to study the intervention effect. Results: The median age was 5.5 years (range 3.0–18.8) and 61.5% were boys. The SDQ filled in by 51 primary caregivers showed no difference between hydrocortisone and placebo in reducing dexamethasone-induced neurobehavioral problems (estimated effect -2.05 (95% confidence interval (CI) -6.00–1.90). Also, no benefit from hydrocortisone compared to placebo was found for reducing sleep problems, hunger, parental stress or improving HRQoL. Conclusions: Hydrocortisone, when compared to placebo, had no additional effect in reducing clinically relevant dexamethasone-induced neurobehavioural problems. Therefore, hydrocortisone is not advised as standard of care for children with ALL who experience dexamethasone-induced neurobehavioural problems. Trial registration: Netherlands Trial Register NTR6695/NL6507 (https://trialsearch.who.int/) and EudraCT 2017–002738–22 (https://eudract.ema.europa.eu/).
UR - http://www.scopus.com/inward/record.url?scp=85156244704&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2023.03.039
DO - 10.1016/j.ejca.2023.03.039
M3 - Article
C2 - 37149961
AN - SCOPUS:85156244704
SN - 0959-8049
VL - 187
SP - 124
EP - 133
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -