At-61 * Dexamethasone Exerts Profound Interference on Treatment Efficacy for Recurrent Glioblastoma
Year: 2014
Type: conference-abstract
Abstract: Dexamethasone is often used to counteract rapid neurologic deterioration in patients with recurrent glioblastoma. We therefore asked whether dexamethasone reduces the efficacy of treatments. The phase III trial comparing tumor-treating alternating electric fields (TTFields) to active chemotherapy offered us a unique opportunity to address this question that was unencumbered by the confounding immune and hematologic side effects of chemotherapy. Using an unsupervised binary partitioning algorithm, we segregated subjects in the trial based on the dexamethasone dose that yielded the greatest overall survival (OS) difference. The median OS of TTFields-treated subjects who used ≤4.1 mg/day of dexamethasone was 11.0 (95% confidence interval [CI] 8.8-16.6) months compared to 4.8 (95%CI 3.9-6.0) months in those who used >4.1 mg of dexamethasone (χ2 = 34.6, P < 0.0001). Subjects who were treated with chemotherapy also benefited from the same lower dose of dexamethasone, median OS 8.9 (95%CI 7.2-16.1) months with ≤4.1 mg/day versus 6.0 (95%CI 3.5-8.3) months with >4.1 mg/day (χ2 = 10.0, P < 0.0015). The same dexamethasone cutoff was validated in a single-institutional cohort with a Karnofsky performance score of ≥70 and treated with either TTFields monotherapy or in combination with bevacizumab. The median OS of patients who used dexamethasone ≤4.1 mg/day was 8.7 (95%CI 6.7-not available [NA]) months compared to those who used >4.1 mg/day was 3.2 (95%CI 1.2-NA) months (χ2 = 11.1, P = 0.0009). A 3-dimensional binary partitioning analysis revealed that the best outcome was from a group of patients with CD4 >144 cells/mm3, CD4/CD8 ≤1.1, dexamethasone ≤0.6 mg/day and their median OS was 13.7 (95%CI 10.8-13.8) months as compared to the rest with a median OS of 4.6 months (95%CI 0.3-22.7). Dexamethasone exerts a profound effect on both TTFields and chemotherapy treatment efficacy in patients with recurrent glioblastoma. Our data strongly suggest that dexamethasone can cause global immunosuppression and this most likely interferes with immune effector function against the tumor.
Source: Neuro-Oncology
Authors: E. T. Wong, E. Lok, S. Gautam, K. D. Swanson
Institution: Beth Israel Deaconess Medical Center
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2019051259