High Grade Gliomas Hg-01. Etoposide Improves Survival in High Grade Glioma: a Meta-analysis

BACKGROUND: Despite standard therapy, high grade gliomas (HGGs) have a very poor prognosis. There are numerous phase I and phase II trials investigating novel agents and multimodal approaches that seek to improve upon survival in these patients. The purpose of this study was to evaluate the therapeutic efficacy of topoisomerase inhibitors in the treatment of HGGs. METHODS: We compared the efficacy of chemotherapy drugs in a meta-analysis of 575 HGG studies, including 42,332 patients. Survival gain was defined as an increase in median overall survival compared to the predicted value as computed by multivariate analysis. RESULTS: Patient cohorts treated with Etoposide (VP-16) had a significant improvement in median overall survival (15.45 months vs. 13.06 months, p 1⁄4 0.031, 48 vs. 739 cohorts) and a significant survival gain advantage (p 1⁄4 0.035) over cohorts treated without VP-16. In contrast, patient cohorts treated with Irinotecan (CPT-11) had a significantly worse median overall survival (9.89 months vs. 13.35 months, p 1⁄4 0.007) and a survival disadvantage (p 1⁄4 0.163) over cohorts treated without CPT-11. Subgroup analyses were performed such as newly diagnosed vs. recurrent, pediatric vs. adult, and glioblastoma multiforme vs. anaplastic astrocytoma. The trend toward a survival advantage for VP-16 and a survival disadvantage for CPT-11 remained, though significance was lost when subgroups became small. CONCLUSION: Results from this study suggest that Etoposide improves overall survival and should be included in chemotherapy regimens for patients being treated for HGGs, whereas Irinotecan should be used cautiously.