A phase II prospective study of standardized steroid dosing for patients with brain metastases undergoing whole brain radiotherapy

Abstract

2050 Background: This study is aimed to prospectively investigate whether lower doses of Dexamethasone (DXM) control neurological symptoms with less side-effects in patients with brain metastases undergoing whole brain radiation therapy (WBRT). Methods: This phase II study had a planned sample size of 50 pts. Pts diagnosed with brain metastases that were on DXM for less than 2 weeks prior to seeing a oncologist and consented to WBRT were eligible. Those with neurological symptoms related to brain metastases were given DXM 8mg qAM, asymptomatic pts received 4mg qAM. First assessment: day 3, then WBRT (20 Gy/5fr). Reassessment: last day of RT, and 2, 4, 8 weeks (w) post RT for symptomatic (1, 3, 8 w for asymptomatic) patients. Neurological symptoms and steroid related side- effects, as reported by patients, were documented. DXM was tapered at the end of WBRT using a pre-established protocol: over 3 w for symptomatic (2 w for asymptomatic) cohort. Primary study outcome was the percentage of pts with significant deviation from the protocol (those who needed higher doses of steroids or to be restarted after tapering). Results: 49 pts were accrued, 40 fully evaluable. 62% of pts deviated from protocol, 95% CI: 46%-77% (56% of asymptomatic, 73% of symptomatic pts); thus, the primary study endpoint was met, and the tapering schedule was deemed inappropriate for clinical use. 24/25 deviations involved an increase in dose or reintroduction of DXM after tapering. Most deviation (15) occurred during or after tapering; 4 were needed for subsequent chemotherapy. Presence of cerebellar metastases was the only statistically significant predictor of pts requiring steroid modification (p value 0.0063). Predominant steroid side-effects graded by patients as little, moderately or very disturbing were increased appetite (73%), peripheral myopathy (58%), insomnia (55%), irritability (50%). Conclusions: Although lower doses of steroids may control neurological symptoms prior to WBRT, the majority of pts required an increase in steroid dose and/or were not able to be tapered according to a pre-determined schedule. Given the side-effects of prolonged steroid use, further attempts at managing and likely individualizing steroid dosing and taper are needed. No significant financial relationships to disclose.