CTNI-43. COMBINATION OF TROFOSFAMIDE PLUS ETOPOSIDE IN RECURRENT ADULT-TYPE DIFFUSE GLIOMAS

Abstract

Abstract Disease relapse almost inevitably occurs in patients with adult-type diffuse glioma. Standard of care treatment options at tumor relapse are still not well defined. Few studies indicate that the combination of trofosfamide plus etoposide (T/E) may be feasible in pediatric glioblastoma patients. We collected clinicopathological data from adult patients with adult-type diffuse glioma treated with the combination of Trofosfamide (100mg/m2/day) and Etoposide (25mg/m2/day) for a minimum of four weeks at the Division of Clinical Neurooncology at the University Hospital Essen. T/E was administered orally in a “one week on, one week off” scheme. A cohort of patients receiving empiric treatment at the investigators’ discretion balanced for tumor entity and canonical prognostic factors served as control. We collected toxicity data as it pertained to CTCAE (Common Terminology Criteria for Adverse Events, version 5.0) and survival data to explore putative efficacy.A total of 33 patients were eligible for this analysis. In the IDH wild-type glioblastoma (n = 18) subgroup, median progression-free survival (3.8 months versus 2.9 months, HR: 2.09, 95% CI: 1.010-4.312, p = 0.0227; PFS-6: 39% versus 6%) and median overall survival (10.4 months versus 5.7 months, HR: 3.05, 95% CI: 1.393-6.655, p = 0.0008) were significantly prolonged as compared to the control cohort. In a multivariable Cox regression analysis, treatment with T/E emerged as statistically significant prognostic marker regarding progression-free survival and overall survival. We observed high-grade adverse events (CTCAE grade III or higher) in 21 (64%) of all recurrent glioma patients with hematotoxicity comprising most adverse events (n = 18, 86%; Lymphopenia: n=13, 62%). This study provides first indication that the combination of T/E is safe in patients with adult-type diffuse gliomas and may be associated with prolonged survival in adult patients with recurrent IDH wildtype glioblastoma. Our data provide a reasonable rationale for follow-up of a larger cohort in a prospective controlled trial.