20 Chapter 1 TREATMENT OF DEXAMETHASONE-INDUCED NEUROBEHAVIORAL PROBLEMS Based on the previously mentioned studies in mice and human, it has been hypothesized that addition of a physiological dose of hydrocortisone during dexamethasone treatment would diminish the neurobehavioral side effects of dexamethasone through refilling of the brain MR.65 This was explored in a randomized clinical trial in 50 pediatric ALL patients: the DexaDays-1 study.35 The safety of addition of a physiological dose of hydrocortisone to dexamethasone treatment was first ensured in a preclinical study, which showed that hydrocortisone did not interfere with the anti-leukemic efficacy of dexamethasone.74 In the total group of pediatric ALL patients, no beneficial effect of hydrocortisone on neurobehavioral or sleep problems was observed (Figure 5). However, in a subgroup of patients with clinically relevant dexamethasone-induced neurobehavioral problems (38%) or clinically relevant sleep problems (19%), hydrocortisone addition showed a significant decrease of the side effects (Figure 5). These results implicated that behavioral and sleep problems may be reduced in children who are most affected. However, despite the significance, since these results were based on a relatively small subgroup, validation in a larger targeted cohort was desired. -30 -20 -10 0 10 20 Effect of hydrocortisone on dexamethasone-induced side effects SDQ SDSC Neurobehavioral problems Sleep problems Total group Clinically significant problems Figure 5. Results of the DexaDays-1 study. The effect of hydrocortisone addition in the total group (blue) and in patients with clinically relevant dexamethasone-induced behavioral (left) or sleep (right) problems (orange). Behavioral problems were measured with the Strengths and Difficulties Questionnaire (SDQ) and sleep problems were measured with the Sleep Disturbance Scale for Children (SDSC). Adapted from Warris et al. Journal of Clinical Oncology 2016.35
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