Dexamethasone Dose Impact Questioned in Recurrent Glioblastoma

Recurrent glioblastoma treatment efficacy may be influenced by dexamethasone therapy for neurological symptoms

medwireNews: Dexamethasone dose may affect overall survival (OS) in patients with recurrent glioblastoma, suggest results from a study comparing tumour-treating alternating electric fields (TTField) and chemotherapy.

“Unlike prior clinical trials, the cohort treated with TTField monotherapy offered us an opportunity to study unambiguously the effect of dexamethasone on patient survival unencumbered by concurrent chemotherapies that suppress the immune system”, explain Eric Wong and team, from Beth Israel Deaconess Medical Center in Boston, Massachusetts, USA.

The phase III trial analysis of patients who received TTField treatment showed that median OS was significantly higher in the 56 individuals given dexamethasone 4.1 mg/day or less than in the 64 patients given a higher dose, at 11.0 versus 4.8 months.

A significant difference was also found in the treatment arm given their best physician’s choice of chemotherapy (BPC), with a median OS of 8.9 months for the 63 patients with a dose at or below the 4.1 mg/day threshold versus 6.0 months for the 54 patients given a higher dose.

Further analysis of survival curves at time points before the median OS revealed a significant difference in OS between the treatment arms only for patients whose dexamethasone dose was 4.1 mg/day or below.

“[E]xtent of dexamethasone exposure not only predicted treatment efficacy but also strongly suggest that TTField therapy is superior to BPC chemotherapy in the setting of low dexamethasone usage”, the researchers comment.

“However, under the influence of higher dexamethasone usage, the benefit of TTField therapy appeared to be negated to a greater extent when compared with BPC chemotherapy as if TTField-treated subjects were not provided with any therapy at all.”

Immunological analysis revealed that median OS was significantly higher in patients with a CD3+ count above 382 cells/mm3 than at or below this level (7.6 vs 2.0 months). This was also true for patients with a CD4+ count greater than 236 cells/mm3 compared with at or below this count (8.0 vs 2.7 months) and a CD8+ count greater than 144 cells/mm3 compared with at or below this threshold (6.8 vs 2.0 months).

Finding that T lymphocyte counts did not correlate with peripheral blood cell counts or dexamethasone dose, the researchers propose they may “serve as an independent measure of immunocompetence in our patients and predict treatment outcome when using [TTField].”

The team concludes in the British Journal of Cancer that their findings “strongly suggest” that both TTField and chemotherapy induce an immune reaction against glioblastoma.

“Future clinical trials for recurrent glioblastoma, as well as other types of brain tumours, may need to take into account the influence of dexamethasone on therapeutic outcome”, they say.

Reference

Wong ET, Lok E, Gautam S, Swanson KD. Dexamethasone exerts profound immunologic interference on treatment efficacy for recurrent glioblastoma. Br J Cancer 2015; Advance online publication 30 June. doi:10.1038/bjc.2015.238

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2015